Microbiome and Human Health: Current Understanding, Engineering, and Enabling TechnologiesClick to copy article linkArticle link copied!
- Nikhil AggarwalNikhil AggarwalNUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore 117456, SingaporeSynthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, SingaporeMore by Nikhil Aggarwal
- Shohei KitanoShohei KitanoNUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore 117456, SingaporeSynthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, SingaporeMore by Shohei Kitano
- Ginette Ru Ying PuahGinette Ru Ying PuahNUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore 117456, SingaporeSynthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, SingaporeWilmar-NUS (WIL@NUS) Corporate Laboratory, National University of Singapore, Singapore 117599, SingaporeWilmar International Limited, Singapore 138568, SingaporeMore by Ginette Ru Ying Puah
- Sandra KittelmannSandra KittelmannWilmar-NUS (WIL@NUS) Corporate Laboratory, National University of Singapore, Singapore 117599, SingaporeWilmar International Limited, Singapore 138568, SingaporeMore by Sandra Kittelmann
- In Young HwangIn Young HwangNUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore 117456, SingaporeSynthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, SingaporeDepartment of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, SingaporeSingapore Institute of Technology, Singapore 138683, SingaporeMore by In Young Hwang
- Matthew Wook Chang*Matthew Wook Chang*E-mail: [email protected]NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore 117456, SingaporeSynthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, SingaporeWilmar-NUS (WIL@NUS) Corporate Laboratory, National University of Singapore, Singapore 117599, SingaporeDepartment of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, SingaporeMore by Matthew Wook Chang
Abstract
The human microbiome is composed of a collection of dynamic microbial communities that inhabit various anatomical locations in the body. Accordingly, the coevolution of the microbiome with the host has resulted in these communities playing a profound role in promoting human health. Consequently, perturbations in the human microbiome can cause or exacerbate several diseases. In this Review, we present our current understanding of the relationship between human health and disease development, focusing on the microbiomes found across the digestive, respiratory, urinary, and reproductive systems as well as the skin. We further discuss various strategies by which the composition and function of the human microbiome can be modulated to exert a therapeutic effect on the host. Finally, we examine technologies such as multiomics approaches and cellular reprogramming of microbes that can enable significant advancements in microbiome research and engineering.
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License Summary*
You are free to share(copy and redistribute) this article in any medium or format and to adapt(remix, transform, and build upon) the material for any purpose, even commercially within the parameters below:
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1. Introduction
2. Human Microbiome
2.1. Factors Influencing the Human Microbiome
2.2. Microbiota in Different Body Parts and Its Relationship with Health/Disease
2.2.1. Digestive System
2.2.1.1. Oral
2.2.1.2. Gastric
2.2.1.3. Intestines
2.2.2. Respiratory System (Nasal, Airway, and Lungs)
2.2.2.1. Nasal
2.2.2.2. Pharynx, Larynx, and Trachea
2.2.2.3. Lungs
2.2.3. Skin
2.2.4. Urinary System
2.2.5. Reproductive System
2.2.5.1. Vaginal
2.3. Summary
body site | predominant microbes | microbiome-associated diseases |
---|---|---|
mouth | bacterial phyla: Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria, Proteobacteria, and Spirochaetes | dental caries (Streptococcus mutans, Streptococcus sobrinus, and Lactobacillus acidophilus) (14,15) |
fungal genera: Candida, Cladosporium, Saccharomycetales, Fusarium, Aspergillus, and Cryptococcus | periodontitis (Streptococcus salivarius may reduce the disease development) (13) | |
stomach | bacterial phyla: Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Fusobacteria | gastric cancer (Helicobacter pylori) (39) |
intestines | bacterial phyla: Firmicutes and Bacteroides | inflammatory bowel disease (lower abundance of Firmicutes) (76−78) |
archaeal species: Methanosphaera stadtmanae and Methanobrevibacter smithii | irritable bowel syndrome, celiac disease, and colorectal cancer (reduction in Lactobacillus species) (80) | |
nose | bacterial phyla: Actinobacteria, Firmicutes, and Proteobacteria | chronic rhinosinusitis (Staphylococcus aureus) (91) |
airway and lungs | bacterial phyla: Firmicutes, Proteobacteria, and Bacteroidetes | asthma (lower abundance of Proteobacteria) (94) |
fungal species: Candida albicans, Ceriporia lacerata, Saccharomyces cerevisiae, and Penicillium brevicompactum | chronic obstructive pulmonary disease (Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis) (95) | |
viruses: Herpesviridae | ||
skin | bacterial phylum: Actinobacteria, Firmicutes, Bacteroidetes, and Proteobacteria | atopic dermatitis (Staphylococcus aureus) (138) |
bladder | bacterial phylum: Firmicutes | urgency urinary incontinence (Lactobacillus gasseri) (144) |
urinary tract infection (Gardnerella vaginalis) (144,148) | ||
vagina | bacterial phylum: Firmicutes (Lactobacillus) | bacterial vaginosis, sexually transmitted infections (not dominated by Lactobacillus) (173,178−181) |
3. Strategies To Engineer the Microbiome for Therapeutic Applications
3.1. Changing the Population Dynamics of the Microbiome
3.1.1. Increasing the Abundance of Specific Members of the Microbiome
3.1.1.1. Probiotic Supplementation
3.1.1.2. Prebiotic Supplementation
3.1.2. Depletion of Specific Members of the Microbiome
3.2. Changing the Functionality of the Microbiome
3.2.1. DNA Conjugation-Mediated Engineering
3.2.2. Use of Enzyme Inhibitors
3.2.3. Microbiome Metabolite Modulation by Engineered Microorganisms
3.3. Natural and Synthetic Microbial Consortia
3.3.1. Fecal Microbiota Transplantation
3.3.2. Synthetic Microbial Consortia
3.4. Current Challenges and Limitations of Microbiome Engineering
strategy | indication | therapeutic microbes/molecules | features | ref |
---|---|---|---|---|
probiotics | obesity and diabetes | A. muciniphila | the bacterium is depleted in patients with obesity, type 2 diabetes, and hypertension | (230) |
obese patients who had received the probiotic for 3 months showed improved insulin sensitivity and reduced cholesterol | ||||
pasteurized bacteria showed higher efficacy compared to live bacteria | ||||
IBD | F. prausnitzii | IBD patients exhibit reduced abundance of F. prausnitzii | (240,241) | |
administration of the bacteria led to reduced disease severity in a mice model of colitis | ||||
no clinical trial conducted yet, likely due to difficult cultivation of the bacteria | ||||
S. boulardii | the probiotic can be used as an adjuvant to induce remission or prevent relapse of IBD | (246) | ||
clinical trials using the probiotics alone have not yet been conducted | ||||
atopic dermatitis | R. mucosa | the bacteria isolated from healthy individuals | (248) | |
treatment with the commensal bacteria led to an improved skin barrier and reduced S. aureus burden | ||||
the therapeutic effect was limited to the bacterial isolate from healthy volunteers and not the patients | ||||
urinary tract infection | L. crispatus CTV-05 | L. crispatus CTV-05 is a vaginal isolate that adheres to the vaginal epithelial layer and suppresses the growth of pathogenic E. coli | (251) | |
in a Phase 2 clinical trial, probiotic administration led to a significant reduction in the recurrent UTI incidence | ||||
prebiotics | atopic dermatitis | mixture of GOS and FOS | GOS and FOS can promote Bifidobacterium growth | (258) |
patients receiving GOS and FOS showed lower incidence of atopic dermatitis with expansion of Bifidobacteria | ||||
Crohn’s disease | FOS | patients receiving FOS showed an improvement in disease and increased fecal Bifidobacteria | (260) | |
colorectal cancer | inulin gel | developed colon-retentive inulin gel that increased the abundance of beneficial bacteria such as Bifidobacteria and Akkermansia | (261) | |
expansion of the beneficial bacteria led to the increased antitumor efficacy of immune checkpoint blockers | ||||
targeted antibiotics | C. difficile infection | ridinilazole | ridinilazole is a small DNA-binding molecule with highly specific action against C. difficile | (269) |
it was found to be superior to standard-of-care vancomycin in a Phase 2 clinical trial | ||||
Gardnerella infection | engineered endolysin PM-447 | bacterial vaginosis caused due to reduced Lactobacillus spp. and increased Gardnerella spp. | (274) | |
engineered endolysin formed by domain shuffling of native enzymes in Gardnerella | ||||
PM-447 has negligible activity against Lactobacillus but can target Gardnerella, including dispersing the biofilm | ||||
bacteriophages | alcoholic hepatitis | bacteriophage against E. faecalis | cytolysin, produced by E. faecalis, is responsible for liver injury in alcoholic hepatitis | (282) |
targeting the bacteria with the phage led to a reduction in liver injury and no significant perturbation of gut microbiome composition | ||||
colorectal cancer | phage against F. nucleatum | phage isolated from human saliva | (283) | |
F. nucleatum causes chemoresistance in colorectal cancer | ||||
by targeting the bacteria with the phage in conjunction with a chemotherapy drug, superior efficacy was observed in mice model | ||||
acne vulgaris | bacteriophages against P. acnes | an aqueous cream formulated comprising bacteriophages against P. acnes isolated from human skin flora | (286) | |
validation only in in vitro model | ||||
enzyme inhibitors | colon cancer | inhibition of bacterial β-glucuronidase | bacterial β-glucuronidase converts the harmless byproduct of the anticancer drug into toxic SN-38 | (307) |
developed enzyme inhibitors neither killed the bacteria nor harmed the mammalian cells | ||||
cardiovascular diseases | inhibition of TMA lyases | microbial TMA lyases involved in the synthesis of TMAO, which is associated with cardiovascular diseases | (308,309) | |
developed inhibitors of TMA lyases are nonlethal to microbes and are able to sustain TMAO decrease in mice models | ||||
engineered microbes | pathogen elimination | commensal and probiotic bacteria | the bacteria is engineered to sense the quorum signaling molecules produced by the pathogen | (288,289) |
in response, the engineered bacteria secretes the antibacterial agent | ||||
hyperammonemia | engineered EcN | EcN was engineered to convert ammonia into l-arginine to boost the urea cycle | (329) | |
biocontainment strategy incorporated into the bacteria for safety | ||||
although effective in various mice models, the bacteria failed to show significant efficacy in Phase 2 clinical trial | ||||
diabetes and obesity | engineered B. subtilis | the bacteria were metabolically rewired to produce 1.5 g/L butyrate in vitro | (334) | |
in an obesity mice model, the engineered bacteria were able to retard weight gain and fat accumulation | ||||
IBD | engineered S. cerevisiae | S. cerevisiae genetically engineered to sense eATP by using a human P2Y2 receptor | (337) | |
in response to eATP, the engineered yeast produces ATP-degrading enzymes | ||||
the engineered microbe performed better than the standard-of-care IBD therapies in a colitis mice model | ||||
natural microbial consortia | recurrent C. difficile infection | fecal microbiota transplantation | fecal sample from healthy donor administered to patients | (341) |
risk of pathogen transmission | ||||
genetics and lifestyle of the recipient may affect efficacy | ||||
SER-109, bacterial spores from healthy donors | oral delivery possible | (352) | ||
reduced risk of pathogen transmission | ||||
clinical efficacy observed in Phase 3 trial | ||||
synthetic microbial consortia | L. monocytogenes infection | 11 bacterial strains from healthy donors | the consortium can induce CD8+ T cells in the intestine | (353) |
cancer | the bacterial strains are low-abundance members of the microbiome | |||
the consortium can enhance the efficacy of immune checkpoint inhibitors in tumor models | ||||
colitis | GUT-108, consortium of 11 bacterial strains | the consortium can perform functions reduced in IBD patients | (355) | |
production of antimicrobial factors to prevent pathogen growth | ||||
induction of anti-inflammatory molecules |
3.4.1. Inadequate Use of Multiomics Studies
3.4.2. Spatiotemporal Control of the Engineered Microbiome
3.4.3. Genetically Intractable Microorganisms
4. Enabling Technologies for Microbiome Research and Engineering
4.1. Functional Omics Approach
4.1.1. Discovery of Novel Metabolites and Biosynthesis
4.1.2. Metatranscriptomics and Metaproteomics
4.1.3. Microbiome Genome-Wide Association Study
4.2. Synthetic Biology and Cellular Reprogramming of Microbes
4.2.1. Regulating Microbe Behavior Using Genetic Logic Circuits
4.2.2. Biosensors and Quorum Sensing
4.2.3. Memory Systems
4.2.4. Kill Switches for Biocontainment and Drug Delivery
4.3. Chassis Engineering
4.3.1. CRISPR-Based Gene-Editing/Manipulation Tools
4.3.2. Genetic Manipulation of Microbes In Situ
5. Challenges and Limitations
Biographies
Acknowledgments
We thank Kamila Isabelle Alabado Navarro for the comments made on the manuscript. We acknowledge the financial support from Investigatorship of the National Research Foundation of Singapore (NRF-NRFI05-2019-0004), NUS Medicine Synthetic Biology Translational Research Programme (NUHSRO/2020/077/MSC/02/SB), the Summit Research Programme of the National University Health System (NUHSRO/2016/053/SRP/05), the Synthetic Biology Initiative of the National University of Singapore (DPRT/943/09/14), ISF-NRF Joint Program of the National Research Foundation of Singapore (NRF2019-NRF-ISF003-3208), the Ministry of Education of Singapore (NUHSRO/2020/046/T1/3), the U.S. Air Force Office of Scientific Research–Asian Office of Aerospace Research and Development (FA2386-18-1-4058), and the Singapore Economic Development Board (S18-139S-IPP-1I). All figures were created using Biorender.com.
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- 7Yatsunenko, T.; Rey, F. E.; Manary, M. J.; Trehan, I.; Dominguez-Bello, M. G.; Contreras, M.; Magris, M.; Hidalgo, G.; Baldassano, R. N.; Anokhin, A. P. Human Gut Microbiome Viewed across Age and Geography. Nature 2012, 486, 222– 227, DOI: 10.1038/nature11053Google Scholar7https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xos1emtLc%253D&md5=40c31ff7028812a7f11d0a230f25d2c2Human gut microbiome viewed across age and geographyYatsunenko, Tanya; Rey, Federico E.; Manary, Mark J.; Trehan, Indi; Dominguez-Bello, Maria Gloria; Contreras, Monica; Magris, Magda; Hidalgo, Glida; Baldassano, Robert N.; Anokhin, Andrey P.; Heath, Andrew C.; Warner, Barbara; Reeder, Jens; Kuczynski, Justin; Caporaso, J. Gregory; Lozupone, Catherine A.; Lauber, Christian; Clemente, Jose Carlos; Knights, Dan; Knight, Rob; Gordon, Jeffrey I.Nature (London, United Kingdom) (2012), 486 (7402), 222-227CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, the authors characterized bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy children and adults from the Amazonas of Venezuela, rural Malawi and US metropolitan areas and included mono- and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-assocd. changes in the genes involved in vitamin biosynthesis and metab. Pronounced differences in bacterial assemblages and functional gene repertoires were noted between US residents and those in the other two countries. These distinctive features are evident in early infancy as well as adulthood. The findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiol. variations and the impact of westernization.
- 8Guigoz, Y.; Dore, J.; Schiffrin, E. J. The Inflammatory Status of Old Age Can Be Nurtured from the Intestinal Environment. Curr. Opin. Clin. Nutr. Metab. Care 2008, 11, 13– 20, DOI: 10.1097/MCO.0b013e3282f2bfdfGoogle Scholar8https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2sjlt1Ogsw%253D%253D&md5=71fcfc2d1caf43b9dec75d568cc7a222The inflammatory status of old age can be nurtured from the intestinal environmentGuigoz Yves; Dore Joel; Schiffrin Eduardo JCurrent opinion in clinical nutrition and metabolic care (2008), 11 (1), 13-20 ISSN:1363-1950.PURPOSE OF REVIEW: Recent studies suggest an association between inflammation status and the presence of chronic disease in the elderly. The review examines publications that address the low level of chronic inflammation and emphasizes how an altered host-microbiota interaction at the gut level could contribute to maintaining a low systemic inflammatory status in the elderly. RECENT FINDINGS: The first population cross-sectional studies with relevant numbers of healthy elderlies show age-related global changes in gut microbiota with a consistent increase in nonpathogenic Gram-negative mainly Enterobacteria and country-specific changes in bifidobacteria. Noninvasive methods have permitted us to detect subclinical intestinal inflammation in the elderly population. Furthermore, few studies report on immune and/or inflammatory response; however, prebiotics, probiotics or synbiotics might improve the inflammatory condition of the elderly. SUMMARY: A better understanding of the mechanisms of host-gut microbiota cross-talk would significantly help in the design of novel nutritional strategies targeting immune reactivity at the mucosal level.
- 9Aas, J. A.; Paster, B. J.; Stokes, L. N.; Olsen, I.; Dewhirst, F. E. Defining the Normal Bacterial Flora of the Oral Cavity. J. Clin. Microbiol. 2005, 43, 5721– 5732, DOI: 10.1128/JCM.43.11.5721-5732.2005Google Scholar9https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2MrptlejtQ%253D%253D&md5=3093bf52de0acfd6c870c49e9bdd817fDefining the normal bacterial flora of the oral cavityAas Jorn A; Paster Bruce J; Stokes Lauren N; Olsen Ingar; Dewhirst Floyd EJournal of clinical microbiology (2005), 43 (11), 5721-32 ISSN:0095-1137.More than 700 bacterial species or phylotypes, of which over 50% have not been cultivated, have been detected in the oral cavity. Our purposes were (i) to utilize culture-independent molecular techniques to extend our knowledge on the breadth of bacterial diversity in the healthy human oral cavity, including not-yet-cultivated bacteria species, and (ii) to determine the site and subject specificity of bacterial colonization. Nine sites from five clinically healthy subjects were analyzed. Sites included tongue dorsum, lateral sides of tongue, buccal epithelium, hard palate, soft palate, supragingival plaque of tooth surfaces, subgingival plaque, maxillary anterior vestibule, and tonsils. 16S rRNA genes from sample DNA were amplified, cloned, and transformed into Escherichia coli. Sequences of 16S rRNA genes were used to determine species identity or closest relatives. In 2,589 clones, 141 predominant species were detected, of which over 60% have not been cultivated. Thirteen new phylotypes were identified. Species common to all sites belonged to the genera Gemella, Granulicatella, Streptococcus, and Veillonella. While some species were subject specific and detected in most sites, other species were site specific. Most sites possessed 20 to 30 different predominant species, and the number of predominant species from all nine sites per individual ranged from 34 to 72. Species typically associated with periodontitis and caries were not detected. There is a distinctive predominant bacterial flora of the healthy oral cavity that is highly diverse and site and subject specific. It is important to fully define the human microflora of the healthy oral cavity before we can understand the role of bacteria in oral disease.
- 10Wade, W. G. The Oral Microbiome in Health and Disease. Pharmacol. Res. 2013, 69, 137– 143, DOI: 10.1016/j.phrs.2012.11.006Google Scholar10https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhvV2rsLfM&md5=a07dae8b4ca5b3900423ba04f0013219The oral microbiome in health and diseaseWade, William G.Pharmacological Research (2013), 69 (1), 137-143CODEN: PHMREP; ISSN:1043-6618. (Elsevier Ltd.)A review. The human mouth harbours one of the most diverse microbiomes in the human body, including viruses, fungi, protozoa, archaea and bacteria. The bacteria are responsible for the two commonest bacterial diseases of man: dental caries (tooth decay) and the periodontal (gum) diseases. Archaea are restricted to a small no. of species of methanogens while around 1000 bacterial species have been found, with representatives from the phyla Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, Spirochaetes, Synergistetes and Tenericutes and the uncultured divisions GN02, SR1 and TM7. Around half of oral bacteria are as yet uncultured and culture-independent methods have been successfully used to comprehensively describe the oral bacterial community. The human oral microbiome database (HOMD, www.homd.org) provides a comprehensive resource consisting of descriptions of oral bacterial taxa, a 16S rRNA identification tool and a repository of oral bacterial genome sequences. Individuals' oral microbiomes are highly specific at the species level, although overall the human oral microbiome shows few geog. differences. Although caries and periodontitis are clearly bacterial diseases, they are not infectious diseases in the classical sense because they result from a complex interaction between the commensal microbiota, host susceptibility and environmental factors such as diet and smoking. Periodontitis, in particular, appears to result from an inappropriate inflammatory reaction to the normal microbiota, exacerbated by the presence of some disease-assocd. bacterial species. In functional terms, there appears to considerable redundancy among the oral microbiota and a focus on functional rather than phylogenetic diversity may be required in order to fully understand host-microbiome interactions.
- 11Kumaraswamy, K. L.; Vidhya, M. Human Papilloma Virus and Oral Infections: An Update. J. Cancer. Res. Ther. 2011, 7, 120– 127, DOI: 10.4103/0973-1482.82915Google Scholar11https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXht1Oru73L&md5=c45d7b04ae6f1c8f8afd53941e75eecfHuman papilloma virus and oral infections: an updateKumaraswamy, K. L.; Vidhya, M.Journal of Cancer Research and Therapeutics (2011), 7 (2), 120-127CODEN: JCRTBK; ISSN:0973-1482. (Medknow Publications and Media Pvt. Ltd.)A review. Human papilloma virus (HPV) is one of the most common virus groups affecting the skin and mucosal areas of the body in the world today. It is also a known fact that HPV causes many lesions in the oral cavity. The most common conditions induced by oral HPV infection are usually benign-like oral papillomas, oral condylomas, and focal epithelial hyperplasia. Oral HPV infection has been found to be assocd. with some cases of oropharyngeal cancer, but it is not the main risk factor for this kind of cancer. HPV is been proved to be the causative agent in causation of cervical cancers without doubt, but its role as a etiol. agent in causing oral cancers needs to be evaluated and studied more to come into any conclusion. We have used review papers, case reports, cohort studies, case control studies, and various internet sources published from 1960 to 2011 to prep. this review of literature.
- 12Wantland, W. W.; Wantland, E. M.; Remo, J. W.; Winquist, D. L. Studies on Human Mouth Protozoa. J. Dent. Res. 1958, 37, 949– 950, DOI: 10.1177/00220345580370052601Google Scholar12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaG1M%252FhslWqtQ%253D%253D&md5=613e26120f803c9dbb791ac4abe20e51Studies on human mouth protozoaWANTLAND W W; WANTLAND E M; REMO J W; WINQUIST D LJournal of dental research (1958), 37 (5), 949-50 ISSN:0022-0345.There is no expanded citation for this reference.
- 13Wescombe, P. A.; Heng, N. C.; Burton, J. P.; Chilcott, C. N.; Tagg, J. R. Streptococcal Bacteriocins and the Case for Streptococcus Salivarius as Model Oral Probiotics. Future Microbiol. 2009, 4, 819– 835, DOI: 10.2217/fmb.09.61Google Scholar13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtVygsrrM&md5=048bb52cccdf0c24604f95298b489f25Streptococcal bacteriocins and the case for Streptococcus salivarius as model oral probioticsWescombe, Philip A.; Heng, Nicholas C. K.; Burton, Jeremy P.; Chilcott, Chris N.; Tagg, John R.Future Microbiology (2009), 4 (7), 819-835CODEN: FMUIAR; ISSN:1746-0913. (Future Medicine Ltd.)A review. Members of the Gram-pos. bacterial genus Streptococcus are a diverse collection of species inhabiting many body sites and range from benign, nonpathogenic species to those causing life-threatening infections. The streptococci are also prolific producers of bacteriocins, which are ribosomally synthesized proteinaceous antibiotics that kill or inhibit species closely related to the producer bacterium. With the emergence of bacterial resistance to conventional antibiotics, there is an impetus to discover, and implement, new and preferably natural' antibiotics to treat or prevent bacterial infections, a niche that bacterial interference therapy mediated by bacteriocins could easily fill. This review focuses on describing the diversity of bacteriocins produced by streptococci and also puts forth a case for Streptococcus salivarius, a nonpathogenic and numerically predominant oral species, as an ideal candidate for development as the model probiotic for the oral cavity. S. salivarius is a safe species that not only produces broad-spectrum bacteriocins but harbors bacteriocin-encoding (and bacteriocin-inducing) transmissible DNA entities (megaplasmids).
- 14Loesche, W. Dental Caries and Periodontitis: Contrasting Two Infections That Have Medical Implications. Infect. Dis. Clin. North. Am. 2007, 21, 471– 502, DOI: 10.1016/j.idc.2007.03.006Google Scholar14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2szks12ksQ%253D%253D&md5=13e95ab1cbb852c9651faf662c146a71Dental caries and periodontitis: contrasting two infections that have medical implicationsLoesche WalterInfectious disease clinics of North America (2007), 21 (2), 471-502, vii ISSN:0891-5520.Both dental decay and periodontal disease are diagnosable and treatable bacterial infections. They are distinctly different infections, with dental decay occurring on the supragingival surfaces of the teeth and periodontal infections occurring in the gingival tissue approximating the subgingival plaque. The bacteria involved and the pathophysiology of these infections are distinctly different.
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- 15Parahitiyawa, N. B.; Scully, C.; Leung, W. K.; Yam, W. C.; Jin, L. J.; Samaranayake, L. P. Exploring the Oral Bacterial Flora: Current Status and Future Directions. Oral Dis. 2010, 16, 136– 145, DOI: 10.1111/j.1601-0825.2009.01607.xGoogle Scholar15https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3c3ksVWjtA%253D%253D&md5=2b38154dd6f1732667394eebfe558a22Exploring the oral bacterial flora: current status and future directionsParahitiyawa N B; Scully C; Leung W K; Yam W C; Jin L J; Samaranayake L POral diseases (2010), 16 (2), 136-45 ISSN:.OBJECTIVE: The oral cavity forms an indispensable part of the human microbiome, for its unique and diverse microflora distributed within various niches. While majority of these organisms exhibit commensalism, shifts in bacterial community dynamics cause pathological changes within oral cavity and distant sites. The aim of this review was to appraise the current and emerging methods of detecting bacteria of the oral cavity paying particular attention to the cultivation independent methods. DESIGN: Literature pertaining to cultivation based and cultivation independent methods of oral bacterial identification was reviewed. METHODS: The specific advantages and disadvantages of cultivation based, microscopic, immunological and metagenomic identification methods were appraised. RESULTS: Because of their fastidious and exacting growth requirements, cultivation based studies grossly underestimate the extent of bacterial diversity in these polymicrobial infections. Culture independent methods deemed more sensitive in identifying difficult to culture and novel bacterial species. CONCLUSION: Apart from characterizing potentially novel bacterial species, the nucleic acid sequence data analyzed using various bioinformatics protocols have revealed that there are in excess of 700 bacterial species inhabiting the mouth. Moreover, the latest pyrosequencing based methods have further broadened the extent of bacterial diversity in oral niches.
- 16Fejerskov, O. Changing Paradigms in Concepts on Dental Caries: Consequences for Oral Health Care. Caries Res. 2004, 38, 182– 191, DOI: 10.1159/000077753Google Scholar16https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXktFKmuro%253D&md5=c504570a2b26ee3439254595de288a91Changing Paradigms in Concepts on Dental Caries: Consequences for Oral Health CareFejerskov, O.Caries Research (2004), 38 (3), 182-191CODEN: CAREBK; ISSN:0008-6568. (S. Karger AG)A review. Kuhn proposed in his Structure of Scientific Revolutions (1962) that the theor. framework of a science (paradigm) dets. how each generation of researchers construes a causal sequence. Paradigm change is infrequent and revolutionary; thereafter previous knowledge and ideas become partially redundant. This paper discusses two paradigms central to cariol. The first concerns the most successful caries-preventive agent: fluoride. When it was thought that fluoride had to be present during tooth mineralization to improve' the biol. apatite and the caries resistance' of the teeth, systemic fluoride administration was necessary for max. benefit. Caries redn. therefore had to be balanced against increasing dental fluorosis. The caries resistance' concept was shown to be erroneous 25 yr ago, but the new paradigm is not yet fully adopted in public health dentistry, so we still await real breakthroughs in more effective use of fluorides for caries prevention. The second paradigm is that caries is a transmittable, infectious disease: even one caused by specific microorganisms. This paradigm would require caries prevention by vaccination, but there is evidence that caries is not a classical infectious disease. Rather it results from an ecol. shift in the tooth-surface biofilm, leading to a mineral imbalance between plaque fluid and tooth and hence net loss of tooth mineral. Therefore, caries belongs to common complex' or multifactorial' diseases, such as cancer, cardiovascular diseases, diabetes, in which many genetic, environmental and behavioral risk factors interact. The paper emphasizes how these paradigm changes raise new research questions which need to be addressed to make caries prevention and treatment more cost-effective.
- 17Filoche, S.; Wong, L.; Sissons, C. H. Oral Biofilms: Emerging Concepts in Microbial Ecology. J. Dent. Res. 2010, 89, 8– 18, DOI: 10.1177/0022034509351812Google Scholar17https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtFOks78%253D&md5=f7bc17db66dde8c2dfb6b940d5cbc06dOral biofilms: emerging concepts in microbial ecologyFiloche, S.; Wong, L.; Sissons, C. H.Journal of Dental Research (2010), 89 (1), 8-18CODEN: JDREAF; ISSN:0022-0345. (Sage Publications)A review. Oral biofilms develop under a range of different conditions and different environments. This review will discuss emerging concepts in microbial ecol. and how they relate to oral biofilm development and the treatment of oral diseases. Clues to how oral biofilms develop may lie in other complex systems, such as interactions between host and gut microbiota, and even in factors that affect biofilm development on leaf surfaces. Most of the conditions under which oral biofilms develop are tightly linked to the overall health and biol. of the host. Advances in mol. techniques have led to a greater appreciation of the diversity of human microbiota, the extent of interactions with the human host, and how that relates to inter-individual variation. As a consequence, plaque development may no longer be thought of as a generic process, but rather as a highly individualized process, which has ramifications for the treatment of the diseases it causes.
- 18Zarco, M. F.; Vess, T. J.; Ginsburg, G. S. The Oral Microbiome in Health and Disease and the Potential Impact on Personalized Dental Medicine. Oral Dis. 2012, 18, 109– 120, DOI: 10.1111/j.1601-0825.2011.01851.xGoogle Scholar18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC387kslGgsg%253D%253D&md5=b8d0943f9a63fb18e95b1b507c4e1a7dThe oral microbiome in health and disease and the potential impact on personalized dental medicineZarco M F; Vess T J; Ginsburg G SOral diseases (2012), 18 (2), 109-20 ISSN:.Every human body contains a personalized microbiome that is essential to maintaining health but capable of eliciting disease. The oral microbiome is particularly imperative to health because it can cause both oral and systemic disease. The oral microbiome rests within biofilms throughout the oral cavity, forming an ecosystem that maintains health when in equilibrium. However, certain ecological shifts in the microbiome allow pathogens to manifest and cause disease. Severe forms of oral disease may result in systemic disease at different body sites. Microbiomics and metagenomics are two fields of research that have emerged to identify the presence of specific microbes in the body and understand the nature of the microbiome activity during both health and disease. The analysis of the microbiome and its genomes will pave the way for more effective therapeutic and diagnostic techniques and, ultimately, contribute to the development of personalized medicine and personalized dental medicine.
- 19Horz, H. P.; Conrads, G. Diagnosis and Anti-Infective Therapy of Periodontitis. Expert Rev. Anti. Infect. Ther. 2007, 5, 703– 715, DOI: 10.1586/14787210.5.4.703Google Scholar19https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtVGjsbvN&md5=04ac697047cb041373c60fca540ed7a3Diagnosis and anti-infective therapy of periodontitisHorz, Hans-Peter; Conrads, GeorgExpert Review of Anti-Infective Therapy (2007), 5 (4), 703-715CODEN: ERATCK; ISSN:1478-7210. (Future Drugs Ltd.)A review. Periodontal diseases (gingivitis and periodontitis) are chronic bacterial infections with a remarkably high prevalence and morbidity. Periodontitis, in contrast to gingivitis, is not reversible, is assocd. with certain bacterial species and affects all of the soft tissue and bone that support teeth. Among the periodontal pathogens, species, such as Aggregatibacter (Actinobacillus) actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythensis, and several forms of uncultivable spirochetes play the major role in the pathogenesis. In severe chronic, recurrent and esp. aggressive forms of periodontitis, diagnosis of the species involved and, whenever possible, an optimized evidence-based antimicrobial treatment is indicated. In order to monitor alarming bacterial changes in the periodontal pocket, several techniques, namely microscopy, culture, immunoassays, enzyme tests and DNA-based techniques, have been established and the methods are described in the first part of this review. In the second part, the selection and use of locally delivered (topical) and systemic antibiotics used adjunctively in periodontal therapy are discussed.
- 20Williams, R. C.; Barnett, A. H.; Claffey, N.; Davis, M.; Gadsby, R.; Kellett, M.; Lip, G. Y.; Thackray, S. The Potential Impact of Periodontal Disease on General Health: A Consensus View. Curr. Med. Res. Opin. 2008, 24, 1635– 1643, DOI: 10.1185/03007990802131215Google Scholar20https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1czovFOguw%253D%253D&md5=492b85b2794cdd7097940360a4702cdcThe potential impact of periodontal disease on general health: a consensus viewWilliams R C; Barnett A H; Claffey N; Davis M; Gadsby R; Kellett M; Lip G Y H; Thackray SCurrent medical research and opinion (2008), 24 (6), 1635-43 ISSN:.BACKGROUND: Evidence for a link between periodontal disease and several systemic diseases is growing rapidly. The infectious and inflammatory burden of chronic periodontitis is thought to have an important systemic impact. Current evidence suggests that periodontitis is associated with an increased likelihood of coronary heart disease and may influence the severity of diabetes. SCOPE: This paper represents a UK and Ireland cross-specialty consensus review, undertaken by a group of physicians and dentists. The consensus group reviewed published evidence (PubMed search for review and original articles), focusing on the past 5 years, on the contributory role of periodontal disease to overall health. In particular, evidence relating to a role for periodontal disease in cardiovascular disease and in diabetes was considered. FINDINGS: Initial studies of large epidemiological data sets have sought to find links between periodontitis and systemic disease outcomes, but a causal relationship still needs to be demonstrated between periodontal disease, cardiovascular disease and diabetes through prospective studies. There is a need for prospective studies assessing the association between periodontal disease and patients at particular risk of cardiovascular events which will allow assessment of both cardiovascular disease clinical endpoints and surrogate markers of cardiovascular risk. Of note, periodontal disease is also often more severe in subjects with diabetes mellitus, a group at already increased risk for cardiovascular events. CONCLUSIONS: While further research is needed to define the population-attributable risk of periodontal disease to both cardiovascular diseases and to diabetes control and progression, health education to encourage better oral health should be considered as part of current healthy lifestyle messages designed to reduce the increasing health burden of obesity, cardiovascular disease and diabetes.
- 21Li, X.; Kolltveit, K. M.; Tronstad, L.; Olsen, I. Systemic Diseases Caused by Oral Infection. Clin. Microbiol. Rev. 2000, 13, 547– 558, DOI: 10.1128/CMR.13.4.547Google Scholar21https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD3M%252FjslSltg%253D%253D&md5=48614e05686ffdf5d23cabab38a387e5Systemic diseases caused by oral infectionLi X; Kolltveit K M; Tronstad L; Olsen IClinical microbiology reviews (2000), 13 (4), 547-58 ISSN:0893-8512.Recently, it has been recognized that oral infection, especially periodontitis, may affect the course and pathogenesis of a number of systemic diseases, such as cardiovascular disease, bacterial pneumonia, diabetes mellitus, and low birth weight. The purpose of this review is to evaluate the current status of oral infections, especially periodontitis, as a causal factor for systemic diseases. Three mechanisms or pathways linking oral infections to secondary systemic effects have been proposed: (i) metastatic spread of infection from the oral cavity as a result of transient bacteremia, (ii) metastatic injury from the effects of circulating oral microbial toxins, and (iii) metastatic inflammation caused by immunological injury induced by oral microorganisms. Periodontitis as a major oral infection may affect the host's susceptibility to systemic disease in three ways: by shared risk factors; subgingival biofilms acting as reservoirs of gram-negative bacteria; and the periodontium acting as a reservoir of inflammatory mediators. Proposed evidence and mechanisms of the above odontogenic systemic diseases are given.
- 22Vieira, A. T.; Castelo, P. M.; Ribeiro, D. A.; Ferreira, C. M. Influence of Oral and Gut Microbiota in the Health of Menopausal Women. Front. Microbiol. 2017, 8, 1884, DOI: 10.3389/fmicb.2017.01884Google Scholar22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1M7gvVyltQ%253D%253D&md5=39ee0e1ecb43fbaff42f38f7f259c5bcInfluence of Oral and Gut Microbiota in the Health of Menopausal WomenVieira Angelica T; Castelo Paula M; Ferreira Caroline M; Castelo Paula M; Ribeiro Daniel A; Ferreira Caroline M; Ribeiro Daniel AFrontiers in microbiology (2017), 8 (), 1884 ISSN:1664-302X.Sex differences in gut microbiota are acknowledged, and evidence suggests that gut microbiota may have a role in higher incidence and/or severity of autoimmune diseases in females. Additionally, it has been suggested that oral, vaginal, and gut microbiota composition can be regulated by estrogen levels. The association of vaginal microbiota with vulvovaginal atrophy at menopause is well described in the literature. However, the relevance of oral and gut microbiota modulation in the immune system during estrogen deficiency and its effect on inflammatory diseases is not well explored. Estrogen deficiency is a condition that occurs in menopausal women, and it can last approximately 30 years of a woman's life. The purpose of this mini- review is to highlight the importance of alterations in the oral and gut microbiota during estrogen deficiency and their effect on oral and inflammatory diseases that are associated with menopause. Considering that hormone replacement therapy is not always recommended or sufficient to prevent or treat menopause-related disease, we will also discuss the use of probiotics and prebiotics as an option for the prevention or treatment of these diseases.
- 23Do, L. G.; Ha, D. H.; Bell, L. K.; Devenish, G.; Golley, R. K.; Leary, S. D.; Manton, D. J.; Thomson, W. M.; Scott, J. A.; Spencer, A. J. Study of Mothers’ and Infants’ Life Events Affecting Oral Health (Smile) Birth Cohort Study: Cohort Profile. BMJ. Open 2020, 10, e041185 DOI: 10.1136/bmjopen-2020-041185Google ScholarThere is no corresponding record for this reference.
- 24Craig, S. J. C.; Blankenberg, D.; Parodi, A. C. L.; Paul, I. M.; Birch, L. L.; Savage, J. S.; Marini, M. E.; Stokes, J. L.; Nekrutenko, A.; Reimherr, M. Child Weight Gain Trajectories Linked to Oral Microbiota Composition. Sci. Rep. 2018, 8, 14030, DOI: 10.1038/s41598-018-31866-9Google Scholar24https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3czgsFWlug%253D%253D&md5=0a4652d9eb464dc9648fabf2165abe6eChild Weight Gain Trajectories Linked To Oral Microbiota CompositionCraig Sarah J C; Paul Ian M; Reimherr Matthew; Chiaromonte Francesca; Makova Kateryna D; Craig Sarah J C; Makova Kateryna D; Blankenberg Daniel; Nekrutenko Anton; Blankenberg Daniel; Parodi Alice Carla Luisa; Paul Ian M; Stokes Jennifer L; Birch Leann L; Savage Jennifer S; Marini Michele E; Savage Jennifer S; Reimherr Matthew; Chiaromonte Francesca; Chiaromonte FrancescaScientific reports (2018), 8 (1), 14030 ISSN:.Gut and oral microbiota perturbations have been observed in obese adults and adolescents; less is known about their influence on weight gain in young children. Here we analyzed the gut and oral microbiota of 226 two-year-olds with 16S rRNA gene sequencing. Weight and length were measured at seven time points and used to identify children with rapid infant weight gain (a strong risk factor for childhood obesity), and to derive growth curves with innovative Functional Data Analysis (FDA) techniques. We showed that growth curves were associated negatively with diversity, and positively with the Firmicutes-to-Bacteroidetes ratio, of the oral microbiota. We also demonstrated an association between the gut microbiota and child growth, even after controlling for the effect of diet on the microbiota. Lastly, we identified several bacterial genera that were associated with child growth patterns. These results suggest that by the age of two, the oral microbiota of children with rapid infant weight gain may have already begun to establish patterns often seen in obese adults. They also suggest that the gut microbiota at age two, while strongly influenced by diet, does not harbor obesity signatures many researchers identified in later life stages.
- 25Jensen, E. D.; Selway, C. A.; Allen, G.; Bednarz, J.; Weyrich, L. S.; Gue, S.; Pena, A. S.; Couper, J. Early Markers of Periodontal Disease and Altered Oral Microbiota Are Associated with Glycemic Control in Children with Type 1 Diabetes. Pediatr. Diabetes 2021, 22, 474– 481, DOI: 10.1111/pedi.13170Google Scholar25https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXotFWgsro%253D&md5=d68bf63501fad7b84c63733e838cc72bEarly markers of periodontal disease and altered oral microbiota are associated with glycemic control in children with type 1 diabetesJensen, Emilija D.; Selway, Caitlin A.; Allen, Gabrielle; Bednarz, Jana; Weyrich, Laura S.; Gue, Sam; Pena, Alexia S.; Couper, JenniferPediatric Diabetes (2021), 22 (3), 474-481CODEN: PDEIBT; ISSN:1399-5448. (Wiley-Blackwell)To det. the relationship between periodontal disease and glycemic control in children with type 1 diabetes and to characterize the diversity and compn. of their oral microbiota. Cross-sectional study including children with type 1 diabetes recruited from clinics at the Women's and Children's Hospital (Australia). Participants had a comprehensive dental assessment, periodontal examn., and buccal and gingival samples collected for 16S rRNA sequencing. Seventy-seven participants (age 13.3 ± 2.6 years, 38 males, BMI z-score 0.81 ± 0.75) had a diabetes duration of 5.6 ± 3.9 years and median HbA1c of 8.5% (range 5.8-13.3), 69.4 mmol/mol (range 39.9-121.9). Thirty-eight (49%) had early markers of periodontal disease. HbA1c was pos. correlated with plaque index (Rho = 0.34, P = 0.002), gingival index (Rho = 0.30, P = 0.009), bleeding on probing (Rho = 0.44, P = 0.0001) and periodontal pocket depth >3 mm (Rho = 0.21, P = 0.06). A 1% increase in HbA1c was independently assocd. with an av. increase in bleeding on probing of 25% (P = 0.002) and with an increase in the rate of sites with pocket depth >3 mm of 54% (P = 0.003). Higher HbA1c was independently related to increased phylogenetic alpha diversity (P = 0.008) and increased compositional variation (beta diversity P = 0.02) in gingival, but not buccal, microbiota. Brushing frequency, plaque index, and gingival index had a significant effect on microbiota compn., independent of HbA1c. Children with type 1 diabetes showed a continuous relationship between less favorable glycemic control and increased early markers of periodontal disease. Glycemic control was also related to the complexity and richness of the plaque microbiota, with diversity increasing as HbA1c levels increase.
- 26Willis, J. R.; Gabaldon, T. The Human Oral Microbiome in Health and Disease: From Sequences to Ecosystems. Microorganisms 2020, 8, 308, DOI: 10.3390/microorganisms8020308Google Scholar26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtlSjsbrI&md5=21fe6c2012315b99442e7e58dc2d013cThe human oral microbiome in health and disease: from sequences to ecosystemsWillis, Jesse R.; Gabaldon, ToniMicroorganisms (2020), 8 (2), 308CODEN: MICRKN; ISSN:2076-2607. (MDPI AG)The human oral cavity is home to an abundant and diverse microbial community (i.e., the oral microbiome), whose compn. and roles in health and disease have been the focus of intense research in recent years. Thanks to developments in sequencing-based approaches, such as 16S rRNA metabarcoding, whole metagenome shotgun sequencing, or meta-transcriptomics, we now can efficiently explore the diversity and roles of oral microbes, even if unculturable. Recent sequencing-based studies have charted oral ecosystems and how they change due to lifestyle or disease conditions. As studies progress, there is increasing evidence of an important role of the oral microbiome in diverse health conditions, which are not limited to diseases of the oral cavity. This, in turn, opens new avenues for microbiome-based diagnostics and therapeutics that benefit from the easy accessibility of the oral cavity for microbiome monitoring and manipulation. Yet, many challenges remain ahead. In this review, we survey the main sequencing-based methodologies that are currently used to explore the oral microbiome and highlight major findings enabled by these approaches. Finally, we discuss future prospects in the field.
- 27Xue, L.; Zou, X.; Yang, X. Q.; Peng, F.; Yu, D. K.; Du, J. R. Chronic Periodontitis Induces Microbiota-Gut-Brain Axis Disorders and Cognitive Impairment in Mice. Exp. Neurol. 2020, 326, 113176, DOI: 10.1016/j.expneurol.2020.113176Google Scholar27https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsFektLk%253D&md5=b35150cd63f2288f9c2471e351593927Chronic periodontitis induces microbiota-gut-brain axis disorders and cognitive impairment in miceXue, Li; Zou, Xiao; Yang, Xue-Qin; Peng, Fu; Yu, Dong-Ke; Du, Jun-RongExperimental Neurology (2020), 326 (), 113176CODEN: EXNEAC; ISSN:0014-4886. (Elsevier Inc.)Epidemiol. studies suggest that chronic periodontitis (CP) is closely assocd. with the incidence and progression of cognitive impairment. The present study investigated the causal relationship between CP and cognitive decline and the underlying mechanism in mice. Long-term ligature around the left second maxillary molar tooth was used to induce CP in mice. Severe alveolar bone loss and inflammatory changes were obsd. in gingival tissues, accompanied by progressive cognitive deficits during a 12-mo period. We also obsd. cerebral neuronal and synaptic injury and glial activation in this mouse model of CP. Furthermore, CP mice exhibited significant dysbiosis of the oral and gut microbiota, disruption of the intestinal barrier and blood-brain barrier, increases in the serum contents of proinflammatory cytokines and lipopolysaccharide (LPS), and increases in brain LPS levels, Toll-like receptor 4 (TLR4) expression, nuclear factor-κB (NF-κB) nuclear translocation and proinflammatory cytokine mRNA levels. These results indicate that CP may directly induce progressive cognitive decline and its mechanism is probably related to microbiota-gut-brain axis disorders, LPS/TLR4/NF-κB signaling activation and neuroinflammatory responses in mice. Therefore, the microbiota-gut-brain axis may provide the potential strategy for the prevention and treatment of CP-assocd. cognitive impairment.
- 28Lin, D.; Hutchison, K. E.; Portillo, S.; Vegara, V.; Ellingson, J. M.; Liu, J.; Krauter, K. S.; Carroll-Portillo, A.; Calhoun, V. D. Association between the Oral Microbiome and Brain Resting State Connectivity in Smokers. Neuroimage 2019, 200, 121– 131, DOI: 10.1016/j.neuroimage.2019.06.023Google Scholar28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3M3ntVejug%253D%253D&md5=358d01e60a3302e2a8a9b4300650d756Association between the oral microbiome and brain resting state connectivity in smokersLin Dongdong; Hutchison Kent E; Ellingson Jarrod M; Portillo Salvador; Carroll-Portillo Amanda; Vegara Victor; Liu Jingyu; Calhoun Vince D; Krauter Kenneth SNeuroImage (2019), 200 (), 121-131 ISSN:.Recent studies have shown a critical role of the gastrointestinal microbiome in brain and behavior via the complex gut-microbiome-brain axis. However, the influence of the oral microbiome in neurological processes is much less studied, especially in response to the stimuli, such as smoking, within the oral microenvironment. Additionally, given the complex structural and functional networks in brain, our knowledge about the relationship between microbiome and brain function through specific brain circuits is still very limited. In this pilot study, we leveraged next generation sequencing for microbiome and functional neuroimaging technique to enable the delineation of microbiome-brain network links as well as their relationship to cigarette smoking. Thirty smokers and 30 age- and sex-matched nonsmokers were recruited for 16S sequencing of their oral microbial community. Among them, 56 subjects were scanned by resting-state functional magnetic resonance imaging to derive brain functional networks. Statistical analyses were performed to demonstrate the influence of smoking on the oral microbial composition, functional network connectivity, and the associations between microbial shifts and functional network connectivity alternations. Compared to nonsmokers, we found a significant decrease of beta diversity (P = 6 × 10(-3)) in smokers and identified several classes (Betaproteobacteria, Spirochaetia, Synergistia, and Mollicutes) with significant alterations in microbial abundance. Pathway analysis on the predicted KEGG pathways shows that the microbiota with altered abundance are mainly involved in pathways related to cell processes, DNA repair, immune system, and neurotransmitters signaling. One brain functional network connectivity component was identified to have a significant difference between smokers and nonsmokers (P = 0.032), mainly including connectivity between brain default network and other task-positive networks. This brain functional component was also significantly associated with smoking related microbiota, suggesting a correlated cross-individual pattern between smoking-induced oral microbiome dysbiosis and brain functional connectivity alternation, possibly involving immunological and neurotransmitter signaling pathways. This work is the first attempt to link oral microbiome and brain functional networks, and provides support for future work in characterizing the role of oral microbiome in mediating smoking effects on brain activity.
- 29Yang, I.; Arthur, R. A.; Zhao, L.; Clark, J.; Hu, Y.; Corwin, E. J.; Lah, J. The Oral Microbiome and Inflammation in Mild Cognitive Impairment. Exp. Gerontol. 2021, 147, 111273, DOI: 10.1016/j.exger.2021.111273Google Scholar29https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXms1yrt7k%253D&md5=c7535daf195e64e54d7b58d034738cb6The oral microbiome and inflammation in mild cognitive impairmentYang, Irene; Arthur, Robert Adam; Zhao, Liping; Clark, Jasmine; Hu, Yijuan; Corwin, Elizabeth J.; Lah, JamesExperimental Gerontology (2021), 147 (), 111273CODEN: EXGEAB; ISSN:0531-5565. (Elsevier Inc.)Inflammation and immune mechanisms are believed to play important roles in Alzheimers disease pathogenesis. Research supports the link between poor oral health and Alzheimers disease. Periodontal disease and dental caries represent the two most common infections of the oral cavity. This study focused on a precursor to Alzheimers disease, mild cognitive impairment (MCI). Using 16S rRNA sequencing, we characterized and compared the oral microbiome of 68 older adults who met the criteria for MCI or were cognitively normal, then explored relationships between the oral microbiome, diagnostic markers of MCI, and blood markers of systemic inflammation. Two taxa, Pasteurellacae and Lautropia mirabilis were identified to be differentially abundant in this cohort. Although systemic inflammatory markers did not differentiate the two groups, differences in five cerebrospinal fluid inflammatory mediators were identified and had significant assocns. with MCI. Because inflammatory markers may reflect CNS changes, pursuing this line of research could provide opportunities for new diagnostic tools and illuminate mechanisms for prevention and mitigation of Alzheimers disease.
- 30Cunha, F. A.; Cota, L. O. M.; Cortelli, S. C.; Miranda, T. B.; Neves, F. S.; Cortelli, J. R.; Costa, F. O. Periodontal Condition and Levels of Bacteria Associated with Periodontitis in Individuals with Bipolar Affective Disorders: A Case-Control Study. J. Periodontal Res. 2019, 54, 63– 72, DOI: 10.1111/jre.12605Google Scholar30https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3c3otVemtw%253D%253D&md5=68545e68d3351ff9e52b300a0821b856Periodontal condition and levels of bacteria associated with periodontitis in individuals with bipolar affective disorders: A case-control studyCunha Fabiano A; Cota Luis O M; Neves Fernando S; Costa Fernando O; Cortelli Sheila C; Miranda Tais B; Cortelli Jose RJournal of periodontal research (2019), 54 (1), 63-72 ISSN:.OBJECTIVE: To evaluate the epidemiological and microbiological aspects of the potential association between bipolar affective disorder (BAPD) and periodontitis. METHODOLOGY: The present case-control study comprised 176 individuals with BAPD and 176 controls. All individuals underwent a complete full-mouth periodontal examination and microbiological sampling. Data on bleeding on probing, probing depth, and clinical attachment level in all present teeth were recorded. Quantification of total bacterial load and Aggregatibacter actinomycetemcomitans, Treponema denticola, and Porphyromonas gingivalis counts were performed through qPCR. Data were analyzed using univariate analysis, Spearman correlation and multivariate logistic regression. RESULTS: The prevalence of periodontitis was 39.7% among controls and 58.5% among individuals with BAPD (OR = 2.13; 95% CI 1.39-3.27). A. actinomycetemcomitans and P. gingivalis counts were significantly higher in individuals with BPAD and periodontitis. The final multivariate logistic regression revealed that periodontitis was strongly associated with the total bacterial load (OR = 1.91; 95% IC = 1.0-1.99; P < 0.001) and the depressive phase of BPAD (OR = 28.94; 95% IC = 4.44-177.27; P < 0.001). CONCLUSION: BAPD was associated with increased risk for periodontitis. Individuals with BPAD presented higher levels of A. actinomycetemcomitans and P. gingivalis, suggesting that periodontitis could be a co-morbidity frequently found in individuals with BAPD.
- 31Shafquat, A.; Joice, R.; Simmons, S. L.; Huttenhower, C. Functional and Phylogenetic Assembly of Microbial Communities in the Human Microbiome. Trends Microbiol. 2014, 22, 261– 266, DOI: 10.1016/j.tim.2014.01.011Google Scholar31https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXjslOhsLs%253D&md5=ac27e4ab90752402d536d4538627b70fFunctional and phylogenetic assembly of microbial communities in the human microbiomeShafquat, Afrah; Joice, Regina; Simmons, Sheri L.; Huttenhower, CurtisTrends in Microbiology (2014), 22 (5), 261-266CODEN: TRMIEA; ISSN:0966-842X. (Elsevier Ltd.)A review. Microbial communities assocd. with the human body, i.e., the human microbiome, are complex ecologies crit. for normal development and health. The taxonomic and phylogenetic compn. of these communities tends to significantly differ among individuals, precluding the definition of a simple, shared set of 'core' microbes. Here, we review recent evidence and ecol. theory supporting the assembly of host-assocd. microbial communities in terms of functional traits rather than specific organisms. That is, distinct microbial species may be responsible for specific host-assocd. functions and phenotypes in distinct hosts. We discuss how ecol. processes (selective and stochastic forces) governing the assembly of metazoan communities can be adapted to describe microbial ecologies in host-assocd. environments, resulting in both niche-specific and 'core' metabolic and other pathways maintained throughout the human microbiome. The extent to which phylogeny and functional traits are linked in host-assocd. microbes, as opposed to unlinked by mechanisms, such as lateral transfer, remains to be detd. However, the definition of these functional assembly rules within microbial communities using controlled model systems and integrative 'omics' represents a fruitful opportunity for mol. systems ecol.
- 32Baker, J. L.; Bor, B.; Agnello, M.; Shi, W.; He, X. Ecology of the Oral Microbiome: Beyond Bacteria. Trends Microbiol. 2017, 25, 362– 374, DOI: 10.1016/j.tim.2016.12.012Google Scholar32https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXitlajsA%253D%253D&md5=cdff0d55a691be9e823d2a61ffd0009fEcology of the Oral Microbiome: Beyond BacteriaBaker, Jonathon L.; Bor, Batbileg; Agnello, Melissa; Shi, Wenyuan; He, XuesongTrends in Microbiology (2017), 25 (5), 362-374CODEN: TRMIEA; ISSN:0966-842X. (Elsevier Ltd.)A review. Although great strides have been made in understanding the complex bacterial community inhabiting the human oral cavity, for a variety of (mainly tech.) reasons the ecol. contributions of oral fungi, viruses, phages, and the candidate phyla radiation (CPR) group of ultrasmall bacteria have remained understudied. Several recent reports have illustrated the diversity and importance of these organisms in the oral cavity, while TM7x and Candida albicans have served as crucial paradigms for CPR species and oral fungi, resp. A comprehensive understanding of the oral microbiota and its influence on host health and disease will require a holistic view that emphasizes interactions among different residents within the oral community, as well as their interaction with the host.
- 33Knight, R.; Callewaert, C.; Marotz, C.; Hyde, E. R.; Debelius, J. W.; McDonald, D.; Sogin, M. L. The Microbiome and Human Biology. Annu. Rev. Genomics Hum. Genet. 2017, 18, 65– 86, DOI: 10.1146/annurev-genom-083115-022438Google Scholar33https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXlsFShtrw%253D&md5=8351b09dd6092e720aa56363372c8498The Microbiome and Human BiologyKnight, Rob; Callewaert, Chris; Marotz, Clarisse; Hyde, Embriette R.; Debelius, Justine W.; McDonald, Daniel; Sogin, Mitchell L.Annual Review of Genomics and Human Genetics (2017), 18 (), 65-86CODEN: ARGHC4; ISSN:1527-8204. (Annual Reviews)Over the past few years, microbiome research has dramatically reshaped our understanding of human biol. New insights range from an enhanced understanding of how microbes mediate digestion and disease processes (e.g., in inflammatory bowel disease) to surprising assocns. with Parkinson's disease, autism, and depression. In this review, we describe how new generations of sequencing technol., anal. advances coupled to new software capabilities, and the integration of animal model data have led to these new discoveries. We also discuss the prospects for integrating studies of the microbiome, metabolome, and immune system, with the goal of elucidating mechanisms that govern their interactions. This systems-level understanding will change how we think about ourselves as organisms.
- 34Yang, I.; Nell, S.; Suerbaum, S. Survival in Hostile Territory: The Microbiota of the Stomach. FEMS Microbiol. Rev. 2013, 37, 736– 761, DOI: 10.1111/1574-6976.12027Google Scholar34https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsVSqtLrK&md5=1c0dda6257924b9e35a1395d58d7a254Survival in hostile territory: the microbiota of the stomachYang, Ines; Nell, Sandra; Suerbaum, SebastianFEMS Microbiology Reviews (2013), 37 (5), 736-761CODEN: FMREE4; ISSN:0168-6445. (Wiley-Blackwell)A review. The human stomach is a formidable barrier to orally ingested microorganisms and was long thought to be sterile. The discovery of Helicobacter pylori, a carcinogenic bacterial pathogen that infects the stomach mucosa of more than one half of all humans globally, has started a major paradigm shift in our understanding of the stomach as an ecol. niche for bacteria. The special adaptations that enable H. pylori to colonize this well-protected habitat have been intensively studied over the last three decades. In contrast, our knowledge concerning bacteria other than H. pylori in the human stomach is still quite limited. However, a substantial body of evidence documents convincingly that bacteria can regularly be sampled from the stomachs of healthy adults. Commonly detected phyla include Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria, and characteristic genera are Lactobacillus, Streptococcus, and Propionibacterium. In this review, we summarize the available literature about the gastric microbiota in humans and selected model animals, discuss the methods used in its characterization, and identify gaps in our knowledge that need to be addressed to advance our understanding of the bacterial colonization of the different layers of the gastric mucosa and its potential role in health and disease.
- 35Wu, W. M.; Yang, Y. S.; Peng, L. H. Microbiota in the Stomach: New Insights. J. Dig. Dis. 2014, 15, 54– 61, DOI: 10.1111/1751-2980.12116Google Scholar35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2c7nvFOkug%253D%253D&md5=ac26ed43c1b2ba24d0166c423186c9eaMicrobiota in the stomach: new insightsWu Wen Ming; Yang Yun Sheng; Peng Li HuaJournal of digestive diseases (2014), 15 (2), 54-61 ISSN:.Bacteria are sparsely distributed in the stomach due to the gastric microbicidal barrier. Several innate defenses (low pH, migrating motor complex and the entero-salivary circulation of nitrate) as well as external factors (diet, Helicobacter pylori infection, proton pump inhibitors, antibiotics and stomach diseases) have been shown to influence significantly the microbiota composition in the stomach. In recent years new culture-independent technologies have allowed the investigation of the cross talk that occurs between hosts and stomach-associated microflora, which helps us to understand the role of gastric bacterial flora in the gastrointestinal microbiological system, both in physiological and pathological conditions. Here, we reviewed the literatures related to this topic and set the stage for future developments of the field.
- 36Oren, A.; Garrity, G. M. Valid Publication of the Names of Forty-Two Phyla of Prokaryotes. Int. J. Syst. Evol. Microbiol. 2021, 71, 005056 DOI: 10.1099/ijsem.0.005056Google ScholarThere is no corresponding record for this reference.
- 37Bik, E. M.; Eckburg, P. B.; Gill, S. R.; Nelson, K. E.; Purdom, E. A.; Francois, F.; Perez-Perez, G.; Blaser, M. J.; Relman, D. A. Molecular Analysis of the Bacterial Microbiota in the Human Stomach. Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 732– 737, DOI: 10.1073/pnas.0506655103Google Scholar37https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XhtVOhsrg%253D&md5=30166b0195f0598ffd4f94ebadff1452Molecular analysis of the bacterial microbiota in the human stomachBik, Elisabeth M.; Eckburg, Paul B.; Gill, Steven R.; Nelson, Karen E.; Purdom, Elizabeth A.; Francois, Fritz; Perez-Perez, Guillermo; Blaser, Martin J.; Relman, David A.Proceedings of the National Academy of Sciences of the United States of America (2006), 103 (3), 732-737CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)The microbiota of the human stomach and the influence of Helicobacter pylori colonization on its compn. remain largely unknown. We characterized bacterial diversity within the human gastric mucosa by using a small subunit 16S rDNA clone library approach and analyzed 1,833 sequences generated by broad-range bacterial PCR from 23 gastric endoscopic biopsy samples. A diverse community of 128 phylotypes was identified, featuring diversity at this site greater than previously described. The majority of sequences were assigned to the Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Fusobacteria phyla. Ten percent of the phylotypes were previously uncharacterized, including a Deinococcus-related organism, relatives of which have been found in extreme environments but not reported before in humans. The gastric clone libraries from 19 subjects contained H. pylori rDNA; however, only 12 of these subjects tested pos. for H. pylori by conventional lab. methods. Statistical anal. revealed a large degree of intersubject variability of the gastric ecosystem. The presence of H. pylori did not affect the compn. of the gastric community. This gastric bacterial rDNA data set was significantly different from sequence collections of the human mouth and esophagus described in other studies, indicating that the human stomach may be home to a distinct microbial ecosystem. The gastric microbiota may play important, as-yet-undiscovered roles in human health and disease.
- 38Delgado, S.; Cabrera-Rubio, R.; Mira, A.; Suarez, A.; Mayo, B. Microbiological Survey of the Human Gastric Ecosystem Using Culturing and Pyrosequencing Methods. Microb. Ecol. 2013, 65, 763– 772, DOI: 10.1007/s00248-013-0192-5Google Scholar38https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXlvVWjt7Y%253D&md5=7394f88abd80913d863992798f7d274fMicrobiological Survey of the Human Gastric Ecosystem Using Culturing and Pyrosequencing MethodsDelgado, Susana; Cabrera-Rubio, Raul; Mira, Alex; Suarez, Adolfo; Mayo, BaltasarMicrobial Ecology (2013), 65 (3), 763-772CODEN: MCBEBU; ISSN:0095-3628. (Springer)Stomach mucosa biopsies and gastric juices samples of 12 healthy persons were analyzed by culturing in selective- and non-selective-rich media. Microbial DNA from four mucosal samples was also amplified by nested PCR using universal bacterial primers, and the 16S rDNA amplicons pyrosequenced. The total no. of cultivable microorganisms recovered from the samples ranged from 102 to 104 cfu/g or ml. The isolates were identified at the species level by PCR amplification and sequencing of the 16S rDNA. Isolates belonged mainly to four genera; Propionibacterium, Lactobacillus, Streptococcus and Staphylococcus. A total of 15,622 high-quality 16S rDNA sequence reads were obtained by pyrosequencing from the four mucosal samples. Sequence anal. grouped the reads into 59 families and 69 genera, revealing wide bacterial diversity. Considerable differences in the compn. of the gastric microbiota were obsd. among the subjects, although in all samples the most abundant operational taxonomic units belonged to Streptococcus, Propionibacterium and Lactobacillus. Comparison of the stomach microbiota with that present in other parts of the human gastrointestinal tract revealed distinctive microbial communities. This is the first study in which a combination of culture and culture-independent techniques has been used to explore the bacterial diversity of the human stomach.
- 39Liu, X.; Shao, L.; Liu, X.; Ji, F.; Mei, Y.; Cheng, Y.; Liu, F.; Yan, C.; Li, L.; Ling, Z. Alterations of Gastric Mucosal Microbiota across Different Stomach Microhabitats in a Cohort of 276 Patients with Gastric Cancer. EBioMedicine 2019, 40, 336– 348, DOI: 10.1016/j.ebiom.2018.12.034Google Scholar39https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3cnlsVGrtw%253D%253D&md5=cba4a37e0b8b46d2ed19c567879aa4fdAlterations of gastric mucosal microbiota across different stomach microhabitats in a cohort of 276 patients with gastric cancerLiu Xiaosun; Mei Ying; Yan Chongxian; Shao Li; Liu Xia; Cheng Yiwen; Liu Fengping; Li Lanjuan; Ji Feng; Ling ZongxinEBioMedicine (2019), 40 (), 336-348 ISSN:.BACKGROUND: As part of the tumor microenvironment, the gastric microbiota play vital roles in tumor initiation, progression and metastasis, but stomach microhabitats are not always uniform. We aimed to characterize differences of gastric microbiota in stomach microhabitats associated with gastric cancer (GC) development. METHODS: A cohort of 276 GC patients without preoperative chemotherapy was enrolled retrospectively, and 230 normal, 247 peritumoral and 229 tumoral tissues were obtained for gastric microbiota analysis targeting the 16S rRNA gene by MiSeq sequencing. The microbial diversity and composition, bacterial co-occurrence correlations and predictive functional profiles were compared across different microhabitats. FINDINGS: GC-specific stomach microhabitats, not GC stages or types, determine the composition and diversity of the gastric microbiota. Most notably, bacterial richness was decreased in peritumoral and tumoral microhabitats, and the correlation network of abundant gastric bacteria was simplified in tumoral microhabitat. Helicobacter pylori (HP), Prevotella copri and Bacteroides uniformis were significantly decreased, whereas Prevotella melaninogenica, Streptococcus anginosus and Propionibacterium acnes were increased in tumoral microhabitat. Higher HP colonisation influenced the overall structure of the gastric microbiota in normal and peritumoral microhabitats. PiCRUSt analysis revealed that genes associated with nucleotide transport and metabolism and amino acid transport and metabolism were significantly enriched in tumoral microbiota, while gastric acid secretion was significantly higher in HP positive group of the tumoral microbiota. INTERPRETATION: Our present study provided new insights into the roles of gastric microbiota in different stomach microhabitats in gastric carcinogenesis, especially the pathogenesis of HP. FUND: National Natural Science Foundation of China.
- 40Nardone, G.; Compare, D. The Human Gastric Microbiota: Is It Time to Rethink the Pathogenesis of Stomach Diseases?. United European Gastroenterol. J. 2015, 3, 255– 260, DOI: 10.1177/2050640614566846Google Scholar40https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtlyitr3O&md5=a6730cf0d3575ef11cdbeb4572753272The human gastric microbiota: Is it time to rethink the pathogenesis of stomach diseases?Nardone, Gerardo; Compare, DeboraUnited European Gastroenterology Journal (2015), 3 (3), 255-260CODEN: UEGJAZ; ISSN:2050-6414. (Sage Publications Ltd.)Introduction: Although long thought to be a sterile organ, due to its acid prodn., the human stomach holds a core microbiome. Aim: To provide an update of findings related to gastric microbiota and its link with gastric diseases. Methods: We conducted a systematic review of the literature. Results: The development of culture-independent methods facilitated the identification of many bacteria. Five major phyla have been detected in the stomach: Firmicutes, Bacteroidites, Actinobacteria, Fusobacteria and Proteobacteria. At the genera level, the healthy human stomach is dominated by Prevotella, Streptococcus, Veillonella, Rothia and Haemophilus; however, the compn. of the gastric microbiota is dynamic and affected by such factors as diet, drugs and diseases. The interaction between the pre-existing gastric microbiota and Helicobacter pylori infection might influence an individual's risk of gastric disease, including gastric cancer. Conclusions: The maintenance of bacterial homeostasis could be essential for the stomach's health and highlights the chance for therapeutic interventions targeting the gastric microbiota, even if gastric pH, peristalsis and the mucus layer may prevent bacteria colonization; and the definition of gastric microbiota of the healthy stomach is still an ongoing challenging task.
- 41Sung, J.; Kim, N.; Kim, J.; Jo, H. J.; Park, J. H.; Nam, R. H.; Seok, Y. J.; Kim, Y. R.; Lee, D. H.; Jung, H. C. Comparison of Gastric Microbiota between Gastric Juice and Mucosa by Next Generation Sequencing Method. J. Cancer. Prev. 2016, 21, 60– 65, DOI: 10.15430/JCP.2016.21.1.60Google Scholar41https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28fnslWqsw%253D%253D&md5=ef4f9ba2d765638fea2993797a786adaComparison of Gastric Microbiota Between Gastric Juice and Mucosa by Next Generation Sequencing MethodSung Jihee; Jo Hyun Jin; Nam Ryoung Hee; Jung Hyun Chae; Kim Nayoung; Lee Dong Ho; Kim Jaeyeon; Park Ji Hyun; Seok Yeong-Jae; Kim Yeon-RanJournal of cancer prevention (2016), 21 (1), 60-5 ISSN:2288-3649.BACKGROUND: Not much is known about the role of gastric microbiota except for Helicobacter pylori in human health and disease. In this study, we aimed to detect human gastric microbiota in both gastric mucosa and gastric juice by barcoded 454-pyrosequencing of the 16S rRNA gene and to compare the results from mucosa and juice. METHODS: Gastric biopsies and stomach juices were collected from 4 subjects who underwent standard endoscopy at Seoul National University Bundang Hospital. Gastric microbiota of antral mucosa, corpus mucosa samples, and gastric fluids were analyzed by barcoded 454-pyrosequencing of the 16S rRNA gene. The analysis focused on bacteria, such as H. pylori and nitrosating or nitrate-reducing bacteria. RESULTS: Gastric fluid samples showed higher diversity compared to that of gastric mucosa samples. The mean of operational taxonomic units was higher in gastric fluid than in gastric mucosa. The samples of gastric fluid and gastric mucosa showed different composition of phyla. The composition of H. pylori and Proteobacteria was higher in mucosa samples compared to gastric fluid samples (H. pylori, 66.5% vs. 3.3%, P = 0.033; Proteobacteria, 75.4% vs. 26.3%, P = 0.041), while Actinobacteria, Bacteroidetes, and Firmicutes were proportioned relatively less in mucosa samples than gastric fluid. However there was no significant difference. (Actinobacteria, 3.5% vs. 20.2%, P = 0.312; Bacteroidetes, 6.0% vs. 14.8%, P = 0.329; Firmicutes, 12.8% vs. 33.4%, P = 0.246). CONCLUSIONS: Even though these samples were small, gastric mucosa could be more effective than gastric fluid in the detection of meaningful gastric microbiota by pyrosequencing.
- 42Zilberstein, B.; Quintanilha, A. G.; Santos, M. A. A.; Pajecki, D.; Moura, E. G.; Alves, P. R A.; Filho, F. M.; de Souza, J. A. U.; Gama-Rodrigues, J. Digestive Tract Microbiota in Healthy Volunteers. Clinics 2007, 62, 47– 56, DOI: 10.1590/S1807-59322007000100008Google Scholar42https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2s7lslClsw%253D%253D&md5=0af92868f59dcfe02559b873775985d0Digestive tract microbiota in healthy volunteersZilberstein Bruno; Quintanilha Alina G; Santos Manoel A A; Pajecki Denis; Moura Eduardo G; Alves Paulo Roberto Arruda; Maluf Filho Fauze; de Souza Joao Ary Ubriaco; Gama-Rodrigues JoaquimClinics (Sao Paulo, Brazil) (2007), 62 (1), 47-54 ISSN:1807-5932.PURPOSE: The aim of this study was to standardize the methods of sample collection of mucus from the digestive tract and to determine the microbiota in healthy volunteers from Brazil, collecting samples from the mouth, esophagus, stomach, duodenum, jejunum, ileum, colon, and rectum. METHODS: Microbiota of selected healthy volunteers from the oral cavity (n=10), the esophagus (n=10), the upper digestive tract (n=20), and the lower digestive tract (n=24) were evaluated through distinct collection methods. Collection methods took into account the different sites, using basic scraping and swabbing techniques, stimulated saliva from the oral cavity, irrigation-aspiration with sterile catheters especially designed for the esophagus, a probe especially designed for upper digestive tract, and a special catheter for the lower digestive tract. RESULTS: (i) Mixed microbiota were identified in the oral cavity, predominantly Gram-positive aerobic and anaerobic cocci; (ii) transitional flora mainly in the esophagus; (iii) Veillonella sp, Lactobacillus sp, and Clostridium sp in the stomach and duodenum; (iv) in the jejunum and upper ileum, we observed Bacteroides sp, Proteus sp, and Staphylococcus sp, in addition to Veillonella sp; (v) in the colon, the presence of "nonpathogenic" anaerobic bacteria Veillonella sp (average 10(5) UFC) indicates the existence of a low oxidation-reduction potential environment, which suggests the possibility of adoption of these bacteria as biological markers of total digestive tract health. CONCLUSIONS: The collection methods were efficient in obtaining adequate samples from each segment of the total digestive tract to reveal the normal microbiota. These procedures are safe and easily reproducible for microbiological studies.
- 43Yu, G.; Torres, J.; Hu, N.; Medrano-Guzman, R.; Herrera-Goepfert, R.; Humphrys, M. S.; Wang, L.; Wang, C.; Ding, T.; Ravel, J. Molecular Characterization of the Human Stomach Microbiota in Gastric Cancer Patients. Front. Cell Infect. Microbiol. 2017, 7, 302, DOI: 10.3389/fcimb.2017.00302Google Scholar43https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitl2nsr%252FO&md5=ed0219746cde4e818322c235b5a3e04eMolecular characterization of the human stomach microbiota in gastric cancer patientsYu, Guoqin; Torres, Javier; Hu, Nan; Medrano-Guzman, Rafael; Herrera-Goepfert, Roberto; Humphrys, Michael S.; Wang, Lemin; Wang, Chaoyu; Ding, Ti; Ravel, Jacques; Taylor, Philip R.; Abnet, Christian C.; Goldstein, Alisa M.Frontiers in Cellular and Infection Microbiology (2017), 7 (), 302/1-302/11CODEN: FCIMAB; ISSN:2235-2988. (Frontiers Media S.A.)Helicobacter pylori (Hp) is the primary cause of gastric cancer but we know little of its relative abundance and other microbes in the stomach, esp. at the time of gastric cancer diagnosis. Here we characterized the taxonomic and derived functional profiles of gastric microbiota in two different sets of gastric cancer patients, and compared them with microbial profiles in other body sites. Paired non-malignant and tumor tissues were sampled from 160 gastric cancer patients with 80 from China and 80 from Mexico. The 16S rRNA gene V3-V4 region was sequenced using MiSeq platform for taxonomic profiles. PICRUSt was used to predict functional profiles. Human Microbiome Project was used for comparison. We showed that Hp is the most abundant member of gastric microbiota in both Chinese and Mexican samples (51 and 24%, resp.), followed by oral-assocd. bacteria. Taxonomic (phylum-level) profiles of stomach microbiota resembled oral microbiota, esp. when the Helicobacter reads were removed. The functional profiles of stomach microbiota, however, were distinct from those found in other body sites and had higher inter-subject dissimilarity. Gastric microbiota compn. did not differ by Hp colonization status or stomach anat. sites, but did differ between paired non-malignant and tumor tissues in either Chinese or Mexican samples. Our study showed that Hp is the dominant member of the non-malignant gastric tissue microbiota in many gastric cancer patients. Our results provide insights on the gastric microbiota compn. and function in gastric cancer patients, which may have important clin. implications.
- 44Mitchell, D. R.; Derakhshan, M. H.; Wirz, A. A.; Orange, C.; Ballantyne, S. A.; Going, J. J.; McColl, K. E. L. The Gastric Acid Pocket Is Attenuated in H. Pylori Infected Subjects. Gut 2017, 66, 1555– 1562, DOI: 10.1136/gutjnl-2016-312638Google Scholar44https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitVShurjJ&md5=0cf15a458816f41b143642043313365fThe gastric acid pocket is attenuated in H. pylori infected subjectsMitchell, David R.; Derakhshan, Mohammad H.; Wirz, Angela A.; Orange, Clare; Ballantyne, Stuart A.; Going, James J.; Mccoll, Kenneth E. L.Gut (2017), 66 (9), 1555-1563CODEN: GUTTAK; ISSN:0017-5749. (BMJ Publishing Group)Objective: Gastric acid secretory capacity in different anatomical regions, including the postprandial acid pocket, was assessed in Helicobacter pylori pos. and neg. volunteers in a Western population. Design: We studied 31 H. pylori pos. and 28 H. pylori neg. volunteers, matched for age, gender and body mass index. Jumbo biopsies were taken at 11 predetd. locations from the gastro-oesophageal junction and stomach. Combined high-resoln. pH metry (12 sensors) and manometry (36 sensors) was performed for 20 min fasted and 90 min postprandially. The squamocolumnar junction was marked with radio-opaque clips and visualized radiol. Biopsies were scored for inflammation and d. of parietal, chief and G cells immunohistochem. Results: Under fasting conditions, the H. pylori positives had less intragastric acidity compared with negatives at all sensors >1.1 cm distal to the peak lower oesophageal sphincter (LES) pressure (p<0.01). Postprandially, intragastric acidity was less in H. pylori positives at sensors 2.2, 3.3 and 4.4 cm distal to the peak LES pressure (p<0.05), but there were no significant differences in more distal sensors. The postprandial acid pocket was thus attenuated in H. pylori positives. The H. pylori positives had a lower d. of parietal and chief cells compared with H. pylori negatives in 10 of the 11 gastric locations (p<0.05). 17/31 of the H. pylori positives were CagA-seropos. and showed a more marked redn. in intragastric acidity and increased mucosal inflammation. Conclusions: In population volunteers, H. pylori positives have reduced intragastric acidity which most markedly affects the postprandial acid pocket.
- 45Li, T. H.; Qin, Y.; Sham, P. C.; Lau, K. S.; Chu, K. M.; Leung, W. K. Alterations in Gastric Microbiota after H. Pylori Eradication and in Different Histological Stages of Gastric Carcinogenesis. Sci. Rep. 2017, 7, 44935, DOI: 10.1038/srep44935Google Scholar45https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXkvVKrtL8%253D&md5=100a12466b64d2318aba50e49a5af949Alterations in Gastric Microbiota After H. Pylori Eradication and in Different Histological Stages of Gastric CarcinogenesisLi, Tung Hiu; Qin, Youwen; Sham, Pak Chung; Lau, K. S.; Chu, Kent-Man; Leung, Wai K.Scientific Reports (2017), 7 (), 44935CODEN: SRCEC3; ISSN:2045-2322. (Nature Publishing Group)The role of bacteria other than Helicobacter pylori (HP) in the stomach remains elusive. We characterized the gastric microbiota in individuals with different histol. stages of gastric carcinogenesis and after receiving HP eradication therapy. Endoscopic gastric biopsies were obtained from subjects with HP gastritis, gastric intestinal metaplasia (IM), gastric cancer (GC) and HP neg. controls. Gastric microbiota was characterized by Illumina MiSeq platform targeting the 16 S rDNA. Apart from dominant H. pylori, we obsd. other Proteobacteria including Haemophilus, Serratia, Neisseria and Stenotrophomonas as the major components of the human gastric microbiota. Although samples were largely converged according to the relative abundance of HP, a clear sepn. of GC and other samples was recovered. While there was a strong inverse assocn. between HP relative abundance and bacterial diversity, this assocn. was weak in GC samples which tended to have lower bacterial diversity compared with other samples with similar HP levels. Eradication of HP resulted in an increase in bacterial diversity and restoration of the relative abundance of other bacteria to levels similar to individuals without HP. In conclusion, HP colonization results in alterations of gastric microbiota and redn. in bacterial diversity, which could be restored by antibiotic treatment.
- 46Arumugam, M.; Raes, J.; Pelletier, E.; Le Paslier, D.; Yamada, T.; Mende, D. R.; Fernandes, G. R.; Tap, J.; Bruls, T.; Batto, J. M. Enterotypes of the Human Gut Microbiome. Nature 2011, 473, 174– 180, DOI: 10.1038/nature09944Google Scholar46https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXkvFeisLo%253D&md5=3f8dfb6b1250d9d913e9ecd03984d9d7Enterotypes of the human gut microbiomeArumugam, Manimozhiyan; Raes, Jeroen; Pelletier, Eric; Le Paslier, Denis; Yamada, Takuji; Mende, Daniel R.; Fernandes, Gabriel R.; Tap, Julien; Bruls, Thomas; Batto, Jean-Michel; Bertalan, Marcelo; Borruel, Natalia; Casellas, Francesc; Fernandez, Leyden; Gautier, Laurent; Hansen, Torben; Hattori, Masahira; Hayashi, Tetsuya; Kleerebezem, Michiel; Kurokawa, Ken; Leclerc, Marion; Levenez, Florence; Manichanh, Chaysavanh; Nielsen, H. Bjorn; Nielsen, Trine; Pons, Nicolas; Poulain, Julie; Qin, Junjie; Sicheritz-Ponten, Thomas; Tims, Sebastian; Torrents, David; Ugarte, Edgardo; Zoetendal, Erwin G.; Wang, Jun; Guarner, Francisco; Pedersen, Oluf; de Vos, Willem M.; Brunak, Soren; Dore, Joel; Weissenbach, Jean; Ehrlich, S. Dusko; Bork, Peer; Antolin, Maria; Artiguenave, Francois; Blottiere, Herve M.; Almeida, Mathieu; Brechot, Christian; Cara, Carlos; Chervaux, Christian; Cultrone, Antonella; Delorme, Christine; Denariaz, Gerard; Dervyn, Rozenn; Foerstner, Konrad U.; Friss, Carsten; van de Guchte, Maarten; Guedon, Eric; Haimet, Florence; Huber, Wolfgang; van Hylckama-Vlieg, Johan; Jamet, Alexandre; Juste, Catherine; Kaci, Ghalia; Knol, Jan; Lakhdari, Omar; Layec, Severine; Le Roux, Karine; Maguin, Emmanuelle; Merieux, Alexandre; Melo Minardi, Raquel; M'rini, Christine; Muller, Jean; Oozeer, Raish; Parkhill, Julian; Renault, Pierre; Rescigno, Maria; Sanchez, Nicolas; Sunagawa, Shinichi; Torrejon, Antonio; Turner, Keith; Vandemeulebrouck, Gaetana; Varela, Encarna; Winogradsky, Yohanan; Zeller, GeorgNature (London, United Kingdom) (2011), 473 (7346), 174-180CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)Our knowledge of species and functional compn. of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced fecal metagenomes of individuals from four countries with previously published data sets, the authors identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. They also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited no. of well balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species compn., but abundant mol. functions are not necessarily provided by abundant species, highlighting the importance of a functional anal. to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the obsd. enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.
- 47Eggesbo, M.; Moen, B.; Peddada, S.; Baird, D.; Rugtveit, J.; Midtvedt, T.; Bushel, P. R.; Sekelja, M.; Rudi, K. Development of Gut Microbiota in Infants Not Exposed to Medical Interventions. APMIS 2011, 119, 17– 35, DOI: 10.1111/j.1600-0463.2010.02688.xGoogle Scholar47https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3M%252FlvVSlsw%253D%253D&md5=00cc35f4f709d1b6c35456db05b1d939Development of gut microbiota in infants not exposed to medical interventionsEggesbo Merete; Moen Birgitte; Peddada Shyamal; Baird Donna; Rugtveit Jarle; Midtvedt Tore; Bushel Pierre R; Sekelja Monika; Rudi KnutAPMIS : acta pathologica, microbiologica, et immunologica Scandinavica (2011), 119 (1), 17-35 ISSN:.Knowledge of the composition of a normal healthy gut microbiota during infancy is important for understanding the role of gut microbiota in disease. A limitation of previous studies is that they are based on infants who have been subject to factors, which can have a profound disruptive effect on the natural colonization process. We describe the colonization process, during the first 4 months after birth, in 85 infants who have experienced no major medical or dietary interventions. They were all vaginally delivered, healthy, term infants, who were not exposed to antibiotics, exclusively breastfed during their first month of life and at least partially breastfed up to 4 months. Selected microbial groups were identified by targeting small subunit microbial ribosomal RNA genes. In contrast to more recent studies, but in agreement with older studies, almost all our infants harbored γ-Proteobacteria and Bifidobacterium. Yet undefined non-cultivable species belonging to Bacteroides, as well as microbes identified as Lachnospiraceae 2, were common. Strong associations were observed between some specific constituents of microbiota at day 4 and the concentration of specific microbial groups at day 120, indicating that early gut microbiota may influence later microbiota. Novel information of the undisturbed composition of early gut microbiota in babies is presented.
- 48Karlsson, C. L.; Molin, G.; Cilio, C. M.; Ahrne, S. The Pioneer Gut Microbiota in Human Neonates Vaginally Born at Term-a Pilot Study. Pediatr. Res. 2011, 70, 282– 286, DOI: 10.1203/PDR.0b013e318225f765Google Scholar48https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3MjktFeksA%253D%253D&md5=b90416f924b616bf6a4621e2a6a81aa4The pioneer gut microbiota in human neonates vaginally born at term-a pilot studyKarlsson Caroline L J; Molin Goran; Cilio Corrado M; Ahrne SivPediatric research (2011), 70 (3), 282-6 ISSN:.The pioneer microbiota of the neonate may affect future actions of the immune system. This study aimed to map the pioneer microbiota in healthy neonates vaginally born at term. A subgroup of neonates born large for GA (LGA) was compared with the neonates appropriate for GA (AGA). Fecal samples were collected, within 48 h after birth, from 79 neonates. Quantitative PCR was used for enumeration of Lactobacillus, a subgroup of Lactobacillus common in the vagina, Bifidobacterium, Enterococcus, Enterobacteriaceae, and the Bacteroides fragilis group. Cloning and sequencing were applied for subgroups of neonates born LGA or AGA. Lactobacillus was detected in all neonates, whereas other bacterial groups were detected only in 14 to 30% of the subjects. The prevalence of Gram-negative Proteobacteria was higher in neonates born LGA, whereas Gram-positive Firmicutes was more prevalent in neonates born AGA (p < 0.001). This study contributed to increased knowledge of the pioneer microbiota and indicates that neonates born LGA had significantly different microbiota compared with those born AGA. As the early microbiota can be important for maturation of the immune system, the outcome from this study may be relevant in the care of pregnant woman and newborns.
- 49Biasucci, G.; Rubini, M.; Riboni, S.; Morelli, L.; Bessi, E.; Retetangos, C. Mode of Delivery Affects the Bacterial Community in the Newborn Gut. Early Hum. Dev. 2010, 86, 13– 15, DOI: 10.1016/j.earlhumdev.2010.01.004Google Scholar49https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3cjnsFyhtQ%253D%253D&md5=a4f3eeb6369ea5cd75b123efa22da276Mode of delivery affects the bacterial community in the newborn gutBiasucci Giacomo; Rubini Monica; Riboni Sara; Morelli Lorenzo; Bessi Elena; Retetangos CristianaEarly human development (2010), 86 Suppl 1 (), 13-5 ISSN:.The first colonisation of the intestine is one of the most profound immunological exposures faced by the newborn and it is influenced by external and internal factors. The early composition of human microbiota could have long-lasting metabolic effects and the initial composition of human intestinal bacteria is also known to affect postnatal immune system development, as we are already aware that reduced microbial stimulation during infancy would result in slower postnatal maturation of the immune system and development of an optimal balance between TH1 and TH2-like immunity. Mode of delivery has a major role on the composition of intestinal microbiota in early infancy, as it has been shown that infants born by Caesarean section (CS) have lower numbers of Bifidobacteria and Bacteroides compared with vaginally born infants. We designed a study to investigate the influence of mode of delivery (CS vs. vaginal delivery) on intestinal microbial composition on day 3 of life using PCR-denaturing gradient gel electrophoresis (DGGE) and PCR-temperature gradient gel electrophoresis (TGGE). Both DGGE and TGGE analyses have been used, together with the specific amplifications for 10 Bifidobacterium sp., 3 Ruminococcus sp., and Bacteroides that all have a highly relevant physiological role in the intestinal ecosystem of the newborn. A total of 46 term infants were enrolled in the study, consecutively recruiting all the CS-delivered babies (n=23; 8 males and 15 females) and the immediately following spontaneously delivered babies (n=23; 11 males and 12 females). DGGE analysis carried out with Bifidobacterium-specific primers revealed the presence of this genus in 13 of 23 (56.5%) samples derived from vaginally delivered newborns but in none of the samples obtained from newborns delivered by CS. PCR analysis with Bifidobacterium-species-specific primers showed that naturally delivered infants had a large number of bifidobacterial species, whereas in CS-delivered babies only two samples (8.7%) gave positive results, one for B. longum and another for B. gallicum. In all babies enrolled, micro-organisms belonging to Ruminococcus species were absent and Bacteroides was found in 8.7% of spontaneously delivered babies only. Based on our findings, it seems that newborn's intestinal bacteria during the first 3days of life are strongly influenced by mode of delivery. The intestinal flora of CS and vaginally delivered infants appears to be very different; the former being altered and characterised by a substantial absence of Bifidobacteria sp., the latter characterised by subject-specific microbial profiles, although predominant groups such as B. longum and B. catenulatum could be identified. In summary, mode of delivery does affect the early stage of intestinal bacterial colonisation, which is altered in CS-delivered infants compared with vaginally delivered infants, with only a minor influence of the type of feeding. In addition, the importance of methodological aspects for determining intestinal microbiota in clinical trials requires emphasis if intestinal microbiota composition is to be considered a measure of postnatal adaptation.
- 50Huurre, A.; Kalliomaki, M.; Rautava, S.; Rinne, M.; Salminen, S.; Isolauri, E. Mode of Delivery - Effects on Gut Microbiota and Humoral Immunity. Neonatology 2008, 93, 236– 240, DOI: 10.1159/000111102Google Scholar50https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1czlvFGgtA%253D%253D&md5=8299c82e0214b054b0c8caa7c57c3778Mode of delivery - effects on gut microbiota and humoral immunityHuurre Anu; Kalliomaki Marko; Rautava Samuli; Rinne Minna; Salminen Seppo; Isolauri ErikaNeonatology (2008), 93 (4), 236-40 ISSN:.BACKGROUND: The rate of caesarean deliveries has increased 10-fold worldwide during the past decades. OBJECTIVE: To evaluate differences in the establishment of gut microbiota in infants born by vaginal or caesarean delivery and its impact on mucosal immunity. METHODS: Altogether, 165 consecutive children, prospectively followed from birth at our clinic in Turku, Finland, were gathered; 141 (85%) were born by vaginal delivery and 24 (15%) by caesarean section. Blood was drawn at physician visits for indirect evaluation of mucosal immunity by ELISPOT assay. Faecal samples were obtained for determination of the gut microbiota by fluorescence in situ hybridization of bacterial cells. RESULTS: Infants delivered by caesarean section harboured fewer bifidobacteria at an early age and were shown to mount a stronger humoral immune response. At 1 month of age, the total gut bacterial cell counts per 1 g faeces were higher in vaginally delivered infants (9.9 x 10(9), 95% CI 7.9 x 10(9)-1.2 x 10(10)) as compared to caesarean section delivered (3.1 x 10(9), 95% CI 1.1 x 10(9)-8.6 x 10(9)) (p = 0.001). This distinction was mainly due to the greater number of bifidobacteria in vaginally delivered infants (1.9 x 10(9), 95% CI 6.3 x 10(8)-5.6 x 10(9) vs. 1.5 x 10(6), 95% CI 4.1 x 10(2)-5.7 x 10(9), respectively) (p = 0.001). During the first year of life, the total number of IgA-, IgG- and IgM-secreting cells was lower (p = 0.03, p = 0.02, p = 0.11, respectively) in infants born by vaginal delivery than in those born by caesarean section, possibly reflecting excessive antigen exposure across the vulnerable gut barrier. CONCLUSIONS: Our findings demonstrate that the mode of delivery may have, possibly via gut microbiota development, significant effects on immunological functions in the infant (http://www.clinicaltrials.gov/ct/gui/show/NCT00167700).
- 51Fallani, M.; Young, D.; Scott, J.; Norin, E.; Amarri, S.; Adam, R.; Aguilera, M.; Khanna, S.; Gil, A.; Edwards, C. A. Intestinal Microbiota of 6-Week-Old Infants across Europe: Geographic Influence Beyond Delivery Mode, Breast-Feeding, and Antibiotics. J. Pediatr. Gastroenterol. Nutr. 2010, 51, 77– 84, DOI: 10.1097/MPG.0b013e3181d1b11eGoogle Scholar51https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3cnis1SisQ%253D%253D&md5=2c18a83d8423a279fed067ec4c5a06b1Intestinal microbiota of 6-week-old infants across Europe: geographic influence beyond delivery mode, breast-feeding, and antibioticsFallani Matteo; Young David; Scott Jane; Norin Elisabeth; Amarri Sergio; Adam Rudiger; Aguilera Marga; Khanna Sheila; Gil Angel; Edwards Christine A; Dore JoelJournal of pediatric gastroenterology and nutrition (2010), 51 (1), 77-84 ISSN:.OBJECTIVES: : There are many differences in diet and lifestyle across Europe that may influence the development of the infant gut microbiota. This work aimed to assess the impact of geographic area, mode of delivery, feeding method, and antibiotic treatment on the fecal microbiota of infants from 5 European countries with different lifestyle characteristics: Sweden, Scotland, Germany, Italy, and Spain. PATIENTS AND METHODS: : Fecal samples from 606 infants (age 6 weeks) recruited within the European project INFABIO were analyzed by fluorescent in situ hybridization combined with flow cytometry using a panel of 10 rRNA targeted group- and species-specific oligonucleotide probes. Information on factors potentially affecting gut microbiota composition was collected with questionnaires and associations were evaluated with multivariate analyses. RESULTS: : The Bifidobacterium genus was predominant (40% average proportion of total detectable bacteria), followed by Bacteroides (11.4%) and enterobacteria (7.5%). Northern European countries were associated with higher proportions of bifidobacteria in infant feces, whereas a more diverse microbiota with more bacteroides characterized southern countries. Bifidobacteria dominated the microbiota of breast-fed infants, whereas formula-fed babies had significantly higher proportions of Bacteroides and members of the Clostridium coccoides and Lactobacillus groups. Newborns delivered by cesarean section or from mothers treated with antibiotics perinatally had lower proportions of Bacteroides and members of the Atopobium cluster. CONCLUSIONS: : Delivery mode and feeding method influenced the fecal microbiota of European infants at 6 weeks, as expected, but the effect of country of birth was more pronounced, with dominant bifidobacteria in northern countries and greater early diversification in southern European countries.
- 52Klaassens, E. S.; Boesten, R. J.; Haarman, M.; Knol, J.; Schuren, F. H.; Vaughan, E. E.; de Vos, W. M. Mixed-Species Genomic Microarray Analysis of Fecal Samples Reveals Differential Transcriptional Responses of Bifidobacteria in Breast- and Formula-Fed Infants. Appl. Environ. Microbiol. 2009, 75, 2668– 2676, DOI: 10.1128/AEM.02492-08Google Scholar52https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXlvFWiuro%253D&md5=dcab2b317b9500bb558baac2fb2fd77fMixed-species genomic microarray analysis of fecal samples reveals differential transcriptional responses of bifidobacteria in breast- and formula-fed infantsKlaassens, Eline S.; Boesten, Rolf J.; Haarman, Monique; Knol, Jan; Schuren, Frank H.; Vaughan, Elaine E.; de Vos, Willem M.Applied and Environmental Microbiology (2009), 75 (9), 2668-2676CODEN: AEMIDF; ISSN:0099-2240. (American Society for Microbiology)Although their exact function remains enigmatic, bifidobacteria are among the first colonizers of the newborn infant gut and further develop into abundant communities, notably in response to diet. Therefore, the transcriptional responses of bifidobacteria in rapidly processed fecal samples from young infants that were fed either breast milk or a formula contg. a mixt. of galacto- and fructo-oligosaccharides were studied. The presence and diversity of the bifidobacterial fecal communities were detd. using PCR-denaturing gradient gel electrophoresis and quant. real-time PCR for specific species. Changes in the total no. of bifidobacteria as well as in species diversity were obsd., indicating the metabolic activities of the bifidobacteria within the infant gut. In addn., total RNAs isolated from infant feces were labeled and hybridized to a bifidobacterium-specific microarray comprising approx. 6000 clones of the major bifidobacterial species of the human gut. Approx. 270 clones that showed the most prominent hybridization with the samples were sequenced. Fewer than 10% of the hybridizing clones contained rRNA genes, whereas the vast majority of the inserts showed matches with protein-encoding genes predicted to originate from bifidobacteria. Although a wide range of functional groups was covered by the obtained sequences, the largest fraction (14%) of the transcribed genes assigned to a functional category were predicted to be involved in carbohydrate metab., while some were also implicated in exopolysaccharide prodn. or folate prodn. A total of three of the above-described protein-encoding genes were selected for quant. PCR and sequence analyses, which confirmed the expression of the corresponding genes and the expected nucleotide sequences. In conclusion, the results of this study show the feasibility of obtaining insight into the transcriptional responses of intestinal bifidobacteria by analyzing fecal RNA and highlight the in vivo expression of bifidobacterial genes implicated in host-related functions.
- 53Harmsen, H. J.; Wildeboer-Veloo, A. C.; Raangs, G. C.; Wagendorp, A. A.; Klijn, N.; Bindels, J. G.; Welling, G. W. Analysis of Intestinal Flora Development in Breast-Fed and Formula-Fed Infants by Using Molecular Identification and Detection Methods. J. Pediatr. Gastroenterol. Nutr. 2000, 30, 61– 67, DOI: 10.1097/00005176-200001000-00019Google Scholar53https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD3c%252FpsVWgtQ%253D%253D&md5=da102840648a42cf87388f46f6a2aa49Analysis of intestinal flora development in breast-fed and formula-fed infants by using molecular identification and detection methodsHarmsen H J; Wildeboer-Veloo A C; Raangs G C; Wagendorp A A; Klijn N; Bindels J G; Welling G WJournal of pediatric gastroenterology and nutrition (2000), 30 (1), 61-7 ISSN:0277-2116.BACKGROUND: An obvious difference between breast-fed and formula-fed newborn infants is the development of the intestinal flora, considered to be of importance for protection against harmful micro-organisms and for the maturation of the intestinal immune system. In this study, novel molecular identification methods were used to verify the data obtained by traditional culture methods and to validate the culture independent fluorescent in situ hybridization (FISH) technique. METHODS: From each of six breast-fed and six formula-fed newborn infants, six fecal samples were obtained during the first 20 days of life. The microbial compositions of the samples were analyzed by culturing on specific media and by FISH, by using specific 16S rRNA-targeted oligonucleotide probes. The colonies growing on the media were identified by random amplified polymorphic DNA pattern analysis and by polymerase chain reaction amplification and subsequent analysis of the 16S rRNA gene. RESULTS: Molecular identification of the colonies showed that the selective media are insufficiently selective and unsuitable for quantitative analyses. Qualitative information from the culturing results combined with the data obtained by the FISH technique revealed initial colonization in all infants of a complex (adult-like) flora. After this initial colonization, a selection of bacterial strains began in all infants, in which Bifidobacterium strains played an important role. In all breast-fed infants, bifidobacteria become dominant, whereas in most formula-fed infants similar amounts of Bacteroides and bifidobacteria (approximately 40%) were found. The minor components of the fecal samples from breast-fed infants were mainly lactobacilli and streptococci; samples from formula-fed infants often contained staphylococci, Escherichia coli, and clostridia. CONCLUSIONS: This study confirms the differences in development of intestinal flora between breast-fed and formula-fed infants. The results obtained from the FISH technique were consistent. Although the repertoire of probes for this study was not yet complete, the FISH technique will probably become the method of reference for future studies designed to develop breast-fed-like intestinal flora in formula-fed infants.
- 54Roger, L. C.; McCartney, A. L. Longitudinal Investigation of the Faecal Microbiota of Healthy Full-Term Infants Using Fluorescence in Situ Hybridization and Denaturing Gradient Gel Electrophoresis. Microbiology 2010, 156, 3317– 3328, DOI: 10.1099/mic.0.041913-0Google Scholar54https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsFCiurrE&md5=bacb0afa5f61955f4d243f599991bb01Longitudinal investigation of the faecal microbiota of healthy full-term infants using fluorescence in situ hybridization and denaturing gradient gel electrophoresisRoger, Laure C.; McCartney, Anne L.Microbiology (Reading, United Kingdom) (2010), 156 (11), 3317-3328CODEN: MROBEO; ISSN:1350-0872. (Society for General Microbiology)From birth onwards, the gastrointestinal (GI) tract of infants progressively acquires a complex range of micro-organisms. It is thought that by 2 years of age the GI microbial population has stabilized. Within the developmental period of the infant GI microbiota, weaning is considered to be most crit., as the infant switches from a milk-based diet (breast and/or formula) to a variety of food components. Longitudinal anal. of the biol. succession of the infant GI/fecal microbiota is lacking. In this study, fecal samples were obtained regularly from 14 infants from 1 mo to 18 mo of age. Seven of the infants (including a set of twins) were exclusively breast-fed and seven were exclusively formula-fed prior to weaning, with 175 and 154 fecal samples, resp., obtained from each group. Diversity and dynamics of the infant fecal microbiota were analyzed by using fluorescence in situ hybridization and denaturing gradient gel electrophoresis. Overall, the data demonstrated large inter- and intra-individual differences in the fecal microbiol. profiles during the study period. However, the infant fecal microbiota merged with time towards a climax community within and between feeding groups. Data from the twins showed the highest degree of similarity both quant. and qual. Inter-individual variation was evident within the infant fecal microbiota and its development, even within exclusively formula-fed infants receiving the same diet. These data can be of help to future clin. trials (e.g. targeted weaning products) to organize protocols and obtain a more accurate outline of the changes and dynamics of the infant GI microbiota.
- 55Favier, C. F.; Vaughan, E. E.; De Vos, W. M.; Akkermans, A. D. Molecular Monitoring of Succession of Bacterial Communities in Human Neonates. Appl. Environ. Microbiol. 2002, 68, 219– 226, DOI: 10.1128/AEM.68.1.219-226.2002Google Scholar55https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38Xjt1Wntw%253D%253D&md5=52c2acaf13028809f906cf703dd10ee9Molecular monitoring of succession of bacterial communities in human neonatesFavier, Christine F.; Vaughan, Elaine E.; De Vos, Willem M.; Akkermans, Antoon D. L.Applied and Environmental Microbiology (2002), 68 (1), 219-226CODEN: AEMIDF; ISSN:0099-2240. (American Society for Microbiology)The establishment of bacterial communities in two healthy babies was examd. for more than the first 10 mo of life by monitoring 16S ribosomal DNA (rDNA) diversity in fecal samples by PCR and denaturing gradient gel electrophoresis (DGGE) and by analyzing the sequences of the major ribotypes. DGGE profiles of the dominant populations in the intestines of the infants were obtained by analyzing daily or weekly fecal samples. After delivery, the germ-free infant gastrointestinal tracts were rapidly colonized, and the succession of bacteria in each ecosystem was monitored. During the first few days of life the profiles were simple, but they became more complex as the bacterial diversity increased with time in both babies. Clone libraries of amplified 16S rDNA fragments from baby feces were constructed, and these libraries allowed identification of the bacterial types by comparative DNA sequence anal.; the bacteria identified included members of the genera Bifidobacterium, Ruminococcus, Enterococcus, Clostridium, and Enterobacter. Species most closely related to the genera Bifidobacterium and Ruminococcus in particular dominated the intestinal microbiota based on the stability over time and the nos., as estd. by the intensities of the bands. However, 19 of the 34 cloned rDNA sequences exhibited less than 97% identity with sequences of known bacteria or cloned sequences in databases. This study showed that using PCR-DGGE and 16S rDNA sequence anal. together resulted in a dynamic description of bacterial colonization in the infant intestinal ecosystem and allowed visualization of bacteria that are difficult to cultivate or to detect by other methods.
- 56Fallani, M.; Amarri, S.; Uusijarvi, A.; Adam, R.; Khanna, S.; Aguilera, M.; Gil, A.; Vieites, J. M.; Norin, E.; Young, D. Determinants of the Human Infant Intestinal Microbiota after the Introduction of First Complementary Foods in Infant Samples from Five European Centres. Microbiology 2011, 157, 1385– 1392, DOI: 10.1099/mic.0.042143-0Google Scholar56https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXmvFGgtLw%253D&md5=eab2ba8346208d403df72a0272a8a2aeDeterminants of the human infant intestinal microbiota after the introduction of first complementary foods in infant samples from five European centresFallani, Matteo; Amarri, Sergio; Uusijarvi, Agneta; Adam, Rudiger; Khanna, Sheila; Aguilera, Marga; Gil, Angel; Vieites, Jose M.; Norin, Elisabeth; Young, David; Scott, Jane A.; Dore, Joel; Edwards, Christine A.Microbiology (Reading, United Kingdom) (2011), 157 (5), 1385-1392CODEN: MROBEO; ISSN:1350-0872. (Society for General Microbiology)Although it is well established that early infant feeding has a major influence on the establishment of the gut microbiota, very little is understood about how the introduction of first solid food influences the colonization process. This study aimed to det. the impact of weaning on the faecal microbiota compn. of infants from five European countries (Sweden, Scotland, Germany, Italy and Spain) which have different lifestyle characteristics and infant feeding practices. Faecal samples were collected from 605 infants approx. 4 wk after the introduction of first solid foods and the results were compared with the same infants before weaning (6 wk of age) to investigate the assocn. with detg. factors such as geog. origin, mode of delivery, previous feeding method and age of weaning. Samples were analyzed by fluorescence in situ hybridization and flow cytometry using a panel of 10 rRNA targeted group- and species-specific oligonucleotide probes. The genus Bifidobacterium (36.5 % av. proportion of total detectable bacteria), Clostridium coccoides group (14 %) and Bacteroides (13.6 %) were predominant after weaning. Similar to pre-weaning, northern European countries were assocd. with a higher proportion of bifidobacteria in the infant gut microbiota while higher levels of Bacteroides and lactobacilli characterized southern European countries. As before weaning, the initial feeding method influenced the Clostridium leptum group and Clostridium difficile+Clostridium perfringens species, and bifidobacteria still dominated the faeces of initially breast-fed infants. Formula-fed babies presented significantly higher proportions of Bacteroides and the C. coccoides group. The mode of birth influenced changes in the proportions of bacteroides and atopobium. Although there were significant differences in the mean weaning age between countries, this was not related to the populations of bifidobacteria or bacteroides. Thus, although the faecal microbiota of infants after first complementary foods was different to that before weaning commenced, many of the initial influences on microbiota compn. were still evident.
- 57O’Toole, P. W.; Claesson, M. J. Gut Microbiota: Changes Throughout the Lifespan from Infancy to Elderly. Int. Dairy J. 2010, 20, 281– 291, DOI: 10.1016/j.idairyj.2009.11.010Google Scholar57https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhs1amtrY%253D&md5=5ff512b31ee66ef3b1f4e2a0648ba4f3Gut microbiota: Changes throughout the lifespan from infancy to elderlyO'Toole, Paul W.; Claesson, Marcus J.International Dairy Journal (2010), 20 (4), 281-291CODEN: IDAJE6; ISSN:0958-6946. (Elsevier Ltd.)A review. Our understanding of the compn. and function of the human gut microbiota has improved dramatically in recent years. In this review, major milestones along this path will be reviewed. The methodol. developments that underpinned this acceleration of scientific progress are discussed. We review the infant microbiota with special ref. to colonization, succession and stabilization events. The healthy adult microbiota is then described, including ref. to selected conditions that perturb the microbiota such as antibiotic treatment, bowel dysfunction and obesity. We put special emphasis on the special issues that characterize elderly subjects, including the challenges provided by "inflamm-aging", with ref. to how the microbiota might interact with these processes. Lastly, the elderly intestinal metagenomics project ELDERMET is described, which aims to establish the compn. and function of the gut microbiota in several hundred Irish subjects.
- 58Woodmansey, E. J. Intestinal Bacteria and Ageing. J. Appl. Microbiol. 2007, 102, 1178– 1186, DOI: 10.1111/j.1365-2672.2007.03400.xGoogle Scholar58https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXmslKgtbc%253D&md5=b06f293888a9d1c2eaaa2d5bf52bd12aIntestinal bacteria and ageingWoodmansey, E. J.Journal of Applied Microbiology (2007), 102 (5), 1178-1186CODEN: JAMIFK; ISSN:1364-5072. (Blackwell Publishing Ltd.)A review. Advancements in science and medicine, as well as improved living stds., have led to a steady increase in life expectancy, and subsequently a rise in the elderly population. The intestinal microbiota is important for maintenance of host health, providing energy, nutrients and protection against invading organisms. Although the colonic microbiota is relatively stable throughout adult life, age-related changes in the gastrointestinal (GI) tract, as well as changes in diet and host immune system reactivity, inevitably affect population compn. Recent studies indicate shifts in the compn. of the intestinal microbiota, which may lead to detrimental effects for the elderly host. Increased nos. of facultative anaerobes, in conjunction with a decrease in beneficial organisms such as the anaerobic lactobacilli and bifidobacteria, amongst other anaerobes, have been reported. These changes, along with a general redn. in species diversity in most bacterial groups, and changes to diet and digestive physiol. such as intestinal transit time, may result in increased putrefaction in the colon and a greater susceptibility to disease. Therapeutic strategies to counteract these changes have been suggested in aging people. These include dietary supplements contg. prebiotics, probiotics and a combination of both of these, synbiotics. Limited feeding trials show promising results with these supplements, although further longer-term investigations are required to substantiate their use in elderly health care fields.
- 59Claesson, M. J.; Cusack, S.; O’Sullivan, O.; Greene-Diniz, R.; de Weerd, H.; Flannery, E.; Marchesi, J. R.; Falush, D.; Dinan, T.; Fitzgerald, G. Composition, Variability, and Temporal Stability of the Intestinal Microbiota of the Elderly. Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 4586– 4591, DOI: 10.1073/pnas.1000097107Google Scholar59https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXjvVCkurg%253D&md5=c0e2d62b052f4b56dcf9041be1e32cfcComposition; variability, and temporal stability of the intestinal microbiota of the elderlyClaesson, Marcus J.; Cusack, Siobhbn; O'Sullivan, Orla; Greene-Diniz, Rachel; de Weerd, Heleen; Flannery, Edel; Marchesi, Julian R.; Falush, Daniel; Dinan, Timothy; Fitzgerald, Gerald; Stanton, Catherine; van Sinderen, Douwe; O'Connor, Michael; Harnedy, Norma; O'Connor, Kieran; Henry, Colm; O'Mahony, Denis; Fitzgerald, Anthony P.; Shanahan, Fergus; Twomey, Cillian; Hill, Colin; Ross, R. Paul; O'Toole, Paul W.Proceedings of the National Academy of Sciences of the United States of America (2011), 108 (Suppl. 1), 4586-4591, S4586/1-S4586/11CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Alterations in the human intestinal microbiota are linked to conditions including inflammatory bowel disease, irritable bowel syndrome, and obesity. The microbiota also undergoes substantial changes at the extremes of life, in infants and older people, the ramifications of which are still being explored. We applied pyrosequencing of over 40,000 16S rRNA gene V4 region amplicons per subject to characterize the fecal microbiota in 161 subjects aged 65 y and older and 9 younger control subjects. The microbiota of each individual subject constituted a unique profile that was separable from all others. In 68% of the individuals, the microbiota was dominated by phylum Bacteroides, with an av. proportion of 57% across all 161 baseline samples. Phylum Firmicutes had an av. proportion of 40%. The proportions of some phyla and genera assocd. with disease or health also varied dramatically, including Proteobacteria, Actinobacteria, and Faecalibacteria. The core microbiota of elderly subjects was distinct from that previously established for younger adults, with a greater proportion of Bacteroides spp. and distinct abundance patterns of Clostridium groups. Analyses of 26 fecal microbiota datasets from 3-mo follow-up samples indicated that in 85% of the subjects, the microbiota compn. was more like the corresponding time-0, sample than any other dataset. We conclude that the fecal microbiota of the elderly shows temporal stability over limited time in the majority of subjects but is characterized by unusual phylum proportions and extreme variability.
- 60Flint, H. J.; Scott, K. P.; Louis, P.; Duncan, S. H. The Role of the Gut Microbiota in Nutrition and Health. Nat. Rev. Gastroenterol. Hepatol. 2012, 9, 577– 589, DOI: 10.1038/nrgastro.2012.156Google Scholar60https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsVKmurrF&md5=4cbc7717f95d7f56cfc77674883860abThe role of the gut microbiota in nutrition and healthFlint, Harry J.; Scott, Karen P.; Louis, Petra; Duncan, Sylvia H.Nature Reviews Gastroenterology & Hepatology (2012), 9 (10), 577-589CODEN: NRGHA9; ISSN:1759-5045. (Nature Publishing Group)A review. The microbial communities that colonize different regions of the human gut influence many aspects of health. In the healthy state, they contribute nutrients and energy to the host via the fermn. of nondigestible dietary components in the large intestine, and a balance is maintained with the host's metab. and immune system. Neg. consequences, however, can include acting as sources of inflammation and infection, involvement in gastrointestinal diseases, and possible contributions to diabetes mellitus and obesity. Major progress has been made in defining some of the dominant members of the microbial community in the healthy large intestine, and in identifying their roles in gut metab. Furthermore, it has become clear that diet can have a major influence on microbial community compn. both in the short and long term, which should open up new possibilities for health manipulation via diet. Achieving better definition of those dominant commensal bacteria, community profiles and system characteristics that produce stable gut communities beneficial to health is important. The extent of interindividual variation in microbiota compn. within the population has also become apparent, and probably influences individual responses to drug administration and dietary manipulation. This Review considers the complex interplay between the gut microbiota, diet and health.
- 61Islam, K. B.; Fukiya, S.; Hagio, M.; Fujii, N.; Ishizuka, S.; Ooka, T.; Ogura, Y.; Hayashi, T.; Yokota, A. Bile Acid Is a Host Factor That Regulates the Composition of the Cecal Microbiota in Rats. Gastroenterology 2011, 141, 1773– 1781, DOI: 10.1053/j.gastro.2011.07.046Google Scholar61https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtlOksb3F&md5=1fb04d469fc6e33b893e25bfefbb68afBile Acid Is a Host Factor That Regulates the Composition of the Cecal Microbiota in RatsIslam, K. B. M. Saiful; Fukiya, Satoru; Hagio, Masahito; Fujii, Nobuyuki; Ishizuka, Satoshi; Ooka, Tadasuke; Ogura, Yoshitoshi; Hayashi, Tetsuya; Yokota, AtsushiGastroenterology (2011), 141 (5), 1773-1781CODEN: GASTAB; ISSN:0016-5085. (Elsevier)Background & Aims: Alterations in the gastrointestinal microbiota have been assocd. with metabolic diseases. However, little is known about host factors that induce changes in gastrointestinal bacterial populations. We investigated the role of bile acids in this process because of their strong antimicrobial activities, specifically the effects of cholic acid administration on the compn. of the gut microbiota in a rat model. Methods: Rats were fed diets supplemented with different concns. of cholic acid for 10 days. We used 16S rRNA gene clone library sequencing and fluorescence in situ hybridization to characterize the compn. of the cecal microbiota of the different diet groups. Bile acids in feces, org. acids in cecal contents, and some blood parameters were also analyzed. Results: Administration of cholic acid induced phylum-level alterations in the compn. of the gut microbiota; Firmicutes predominated at the expense of Bacteroidetes. Cholic acid feeding simplified the compn. of the microbiota, with outgrowth of several bacteria in the classes Clostridia and Erysipelotrichi. Externally administered cholic acid was efficiently transformed into deoxycholic acid by a bacterial 7α-dehydroxylation reaction. Serum levels of adiponectin decreased significantly in rats given the cholic acid diet. Conclusions: Cholic acid regulates the compn. of gut microbiota in rats, inducing similar changes to those induced by high-fat diets. These findings improve our understanding of the relationship between metabolic diseases and the compn. of the gastrointestinal microbiota.
- 62Booijink, C. C.; El-Aidy, S.; Rajilic-Stojanovic, M.; Heilig, H. G.; Troost, F. J.; Smidt, H.; Kleerebezem, M.; De Vos, W. M.; Zoetendal, E. G. High Temporal and Inter-Individual Variation Detected in the Human Ileal Microbiota. Environ. Microbiol. 2010, 12, 3213– 3227, DOI: 10.1111/j.1462-2920.2010.02294.xGoogle Scholar62https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXltleisw%253D%253D&md5=d121dc1e0f96b66275c9d5cd9708bc91High temporal and inter-individual variation detected in the human ileal microbiotaBooijink, Carien C. G. M.; El-Aidy, Sahar; Rajilic-Stojanovic, Mirjana; Heilig, Hans G. H. J.; Troost, Freddy J.; Smidt, Hauke; Kleerebezem, Michiel; de Vos, Willem M.; Zoetendal, Erwin G.Environmental Microbiology (2010), 12 (12), 3213-3227CODEN: ENMIFM; ISSN:1462-2912. (Wiley-Blackwell)The diversity and temporal stability of the predominant bacteria in the human ileum was studied with the use of ileal effluent samples of seven individuals with Brooke ileostomies. The total no. of bacteria within the ileal effluent was in the range of 107-108 bacteria per g (wet wt.). The diversity of the bacteria in the ileal effluent showed marked differences compared with that in fecal samples from age-matched healthy adults. The ileal effluent had a higher relative abundance of species within the orders Lactobacillales and Clostridiales, mainly Streptococcus bovis-related species, and the Veillonella group, and a lower proportion of species related to Ruminococcus gnavus, R. obeum and Bacteroides plebeius. In addn., inter-individual differences were found, indicative of a highly personal ileal microbiota profile. Furthermore, temporal profiles showed large fluctuations per individual over a period of 9-28 days (av. similarity over a period of 9 days was as low as 44%), and differences between morning and afternoon profiles were obsd. Parallel cloning and sequencing efforts revealed several phylotypes that were not identified in previous studies (12 out of 65 phylotypes showed less than 97% sequence similarity with previously reported sequences). Achaea were found to be below detection limit by quant. PCR. Overall, the results indicate that the microbiota of the human ileum is relatively unstable, less complex and consisting of different dominating phylotypes when compared with the colonic microbiota.
- 63Zoetendal, E. G.; Raes, J.; van den Bogert, B.; Arumugam, M.; Booijink, C. C.; Troost, F. J.; Bork, P.; Wels, M.; de Vos, W. M.; Kleerebezem, M. The Human Small Intestinal Microbiota Is Driven by Rapid Uptake and Conversion of Simple Carbohydrates. ISME J. 2012, 6, 1415– 1426, DOI: 10.1038/ismej.2011.212Google Scholar63https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XovFylsL8%253D&md5=a904d9c9152db08348e546a1e26dcfa2The human small intestinal microbiota is driven by rapid uptake and conversion of simple carbohydratesZoetendal, Erwin G.; Raes, Jeroen; van den Bogert, Bartholomeus; Arumugam, Manimozhiyan; Booijink, Carien C. G. M.; Troost, Freddy J.; Bork, Peer; Wels, Michiel; de Vos, Willem M.; Kleerebezem, MichielISME Journal (2012), 6 (7), 1415-1426CODEN: IJSOCF; ISSN:1751-7362. (Nature Publishing Group)The human gastrointestinal tract (GI tract) harbors a complex community of microbes. The microbiota compn. varies between different locations in the GI tract, but most studies focus on the fecal microbiota, and that inhabiting the colonic mucosa. Consequently, little is known about the microbiota at other parts of the GI tract, which is esp. true for the small intestine because of its limited accessibility. Here, we deduce an ecol. model of the microbiota compn. and function in the small intestine, using complementing culture-independent approaches. Phylogenetic microarray analyses demonstrated that microbiota compns. that are typically found in effluent samples from ileostomists (subjects without a colon) can also be encountered in the small intestine of healthy individuals. Phylogenetic mapping of small intestinal metagenome of three different ileostomy effluent samples from a single individual indicated that Streptococcus sp., Escherichia coli, Clostridium sp. and high G+C organisms are most abundant in the small intestine. The compns. of these populations fluctuated in time and correlated to the short-chain fatty acids profiles that were detd. in parallel. Comparative functional anal. with fecal metagenomes identified functions that are overrepresented in the small intestine, including simple carbohydrate transport phosphotransferase systems (PTS), central metab. and biotin prodn. Moreover, metatranscriptome anal. supported high level in-situ expression of PTS and carbohydrate metabolic genes, esp. those belonging to Streptococcus sp. Overall, our findings suggest that rapid uptake and fermn. of available carbohydrates contribute to maintaining the microbiota in the human small intestine. The ISME Journal (2012) 6, 1415-1426; doi:10.1038/ismej.2011.212; published online 19 Jan. 2012.
- 64Rinninella, E.; Raoul, P.; Cintoni, M.; Franceschi, F.; Miggiano, G. A. D.; Gasbarrini, A.; Mele, M. C. What Is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases. Microorganisms 2019, 7, 14, DOI: 10.3390/microorganisms7010014Google Scholar64https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXit1ShsbjF&md5=388f6272007c7539cbd95a26581cabefWhat is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseasesRinninella, Emanuele; Raoul, Pauline; Cintoni, Marco; Franceschi, Francesco; Miggiano, Giacinto Abele Donato; Gasbarrini, Antonio; Mele, Maria CristinaMicroorganisms (2019), 7 (1), 14CODEN: MICRKN; ISSN:2076-2607. (MDPI AG)Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metab., maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human's gut microbiota are shaped in early life as their compn. depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota compn. since it is different for each individual. However, a healthy host-microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is assocd. not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurol. disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota compn. should be useful in developing promising therapeutic interventions.
- 65Gill, S. R.; Pop, M.; Deboy, R. T.; Eckburg, P. B.; Turnbaugh, P. J.; Samuel, B. S.; Gordon, J. I.; Relman, D. A.; Fraser-Liggett, C. M.; Nelson, K. E. Metagenomic Analysis of the Human Distal Gut Microbiome. Science 2006, 312, 1355– 1359, DOI: 10.1126/science.1124234Google Scholar65https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XltVOht7c%253D&md5=6164beff8486fc32409a7903c81ad1dcMetagenomic analysis of the human distal gut microbiomeGill, Steven R.; Pop, Mihai; DeBoy, Robert T.; Eckburg, Paul B.; Turnbaugh, Peter J.; Samuel, Buck S.; Gordon, Jeffrey I.; Relman, David A.; Fraser-Liggett, Claire M.; Nelson, Karen E.Science (Washington, DC, United States) (2006), 312 (5778), 1355-1359CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)The human intestinal microbiota is composed of 1013 to 1014 microorganisms whose collective genome ("microbiome") contains at least 100 times as many genes as our own genome. We analyzed ∼78 million base pairs of unique DNA sequence and 2062 polymerase chain reaction-amplified 16S ribosomal DNA sequences obtained from the fecal DNAs of two healthy adults. Using metabolic function analyses of identified genes, we compared our human genome with the av. content of previously sequenced microbial genomes. Our microbiome has significantly enriched metab. of glycans, amino acids, and xenobiotics; methanogenesis; and 2-methyl-D-erythritol 4-phosphate pathway-mediated biosynthesis of vitamins and isoprenoids. Thus, humans are superorganisms whose metab. represents an amalgamation of microbial and human attributes.
- 66Khosravi, A.; Mazmanian, S. K. Disruption of the Gut Microbiome as a Risk Factor for Microbial Infections. Curr. Opin. Microbiol. 2013, 16, 221– 227, DOI: 10.1016/j.mib.2013.03.009Google Scholar66https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3srmtlCmtQ%253D%253D&md5=fe4e073621c9393c36034c99cced359aDisruption of the gut microbiome as a risk factor for microbial infectionsKhosravi Arya; Mazmanian Sarkis KCurrent opinion in microbiology (2013), 16 (2), 221-7 ISSN:.The discovery that microorganisms can be etiologic agents of disease has driven clinical, research and public health efforts to reduce exposure to bacteria. However, despite extensive campaigns to eradicate pathogens (via antibiotics, vaccinations, hygiene, sanitation, etc.), the incidence and/or severity of multiple immune-mediated diseases including, paradoxically, infectious disease have increased in recent decades. We now appreciate that most microbes in our environment are not pathogenic, and that many human-associated bacteria are symbiotic or beneficial. Notably, recent examples have emerged revealing that the microbiome augments immune system function. This review will focus on how commensal-derived signals enhance various aspects of the host response against pathogens. We suggest that modern lifestyle advances may be depleting specific microbes that enhance immunity against pathogens. Validation of the notion that absence of beneficial microbes is a risk factor for infectious disease may have broad implications for future medical practices.
- 67Walker, A. W.; Duncan, S. H.; McWilliam Leitch, E. C.; Child, M. W.; Flint, H. J. Ph and Peptide Supply Can Radically Alter Bacterial Populations and Short-Chain Fatty Acid Ratios within Microbial Communities from the Human Colon. Appl. Environ. Microbiol. 2005, 71, 3692– 3700, DOI: 10.1128/AEM.71.7.3692-3700.2005Google Scholar67https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXmt1ylt7o%253D&md5=49366f46b36a9178f4cd213971eac7f0pH and peptide supply can radically alter bacterial populations and short-chain fatty acid ratios within microbial communities from the human colonWalker, Alan W.; Duncan, Sylvia H.; McWilliam Leitch, E. Carol; Child, Matthew W.; Flint, Harry J.Applied and Environmental Microbiology (2005), 71 (7), 3692-3700CODEN: AEMIDF; ISSN:0099-2240. (American Society for Microbiology)The effects of changes in the gut environment upon the human colonic microbiota are poorly understood. The response of human fecal microbial communities from two donors to alterations in pH (5.5 or 6.5) and peptides (0.6 or 0.1%) was studied here in anaerobic continuous cultures supplied with a mixed carbohydrate source. Final butyrate concns. were markedly higher at pH 5.5 (0.6% peptide mean, 24.9 mM; 0.1% peptide mean, 13.8 mM) than at pH 6.5 (0.6% peptide mean, 5.3 mM; 0.1% peptide mean, 7.6 mM). At pH 5.5 and 0.6% peptide input, a high butyrate prodn. coincided with decreasing acetate concns. The highest propionate concns. (mean, 20.6 mM) occurred at pH 6.5 and 0.6% peptide input. In parallel, major bacterial groups were monitored by using fluorescence in situ hybridization with a panel of specific 16S rRNA probes. Bacteroides levels increased from ∼20 to 75% of total eubacteria after a shift from pH 5.5 to 6.5, at 0.6% peptide, coinciding with high propionate formation. Conversely, populations of the butyrate-producing Roseburia group were highest (11 to 19%) at pH 5.5 but fell at pH 6.5, a finding that correlates with butyrate formation. When tested in batch culture, three Bacteroides species grew well at pH 6.7 but poorly at pH 5.5, which is consistent with the behavior obsd. for the mixed community. Two Roseburia isolates grew equally well at pH 6.7 and 5.5. These findings suggest that a lowering of pH resulting from substrate fermn. in the colon may boost butyrate prodn. and populations of butyrate-producing bacteria, while at the same time curtailing the growth of Bacteroides spp.
- 68Louis, P.; Scott, K. P.; Duncan, S. H.; Flint, H. J. Understanding the Effects of Diet on Bacterial Metabolism in the Large Intestine. J. Appl. Microbiol. 2007, 102, 1197– 1208, DOI: 10.1111/j.1365-2672.2007.03322.xGoogle Scholar68https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXmslKgur4%253D&md5=dc72ea4505d99366375e503972da99f2Understanding the effects of diet on bacterial metabolism in the large intestineLouis, P.; Scott, K. P.; Duncan, S. H.; Flint, H. J.Journal of Applied Microbiology (2007), 102 (5), 1197-1208CODEN: JAMIFK; ISSN:1364-5072. (Blackwell Publishing Ltd.)A review. Recent analyses of rRNA sequence diversity have demonstrated the extent of bacterial diversity in the human colon, and have provided new tools for monitoring changes in the compn. of the gut microbial community. There is now an excellent opportunity to correlate ecol. niches and metabolic activities with particular phylogenetic groups among the microbiota of the human gut. Bacteria that assoc. closely with particulate material and surfaces in the gut include specialized primary degraders of insol. substrates, including resistant starch, plant structural polysaccharides and mucin. Butyrate-producing bacteria found in human faeces belong mainly to the clostridial clusters IV and XIVa. In vitro and in vivo evidence indicates that a group related to Roseburia and Eubacterium rectale plays a major role in mediating the butyrogenic effect of fermentable dietary carbohydrates. Addnl. cluster XIVa species can convert lactate to butyrate, while some members of the clostridial cluster IX convert lactate to propionate. The metabolic outputs of the gut microbial community depend not only on available substrate, but also on the gut environment, with pH playing a major role. Better understanding of the colonic microbial ecosystem will help to explain and predict the effects of dietary additives, including nondigestible carbohydrates, probiotics and prebiotics.
- 69Kho, Z. Y.; Lal, S. K. The Human Gut Microbiome - a Potential Controller of Wellness and Disease. Front. Microbiol. 2018, 9, 1835, DOI: 10.3389/fmicb.2018.01835Google Scholar69https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3c3islyitA%253D%253D&md5=b3201161709507f19e152a0a0481abf2The Human Gut Microbiome - A Potential Controller of Wellness and DiseaseKho Zhi Y; Lal Sunil KFrontiers in microbiology (2018), 9 (), 1835 ISSN:1664-302X.Interest toward the human microbiome, particularly gut microbiome has flourished in recent decades owing to the rapidly advancing sequence-based screening and humanized gnotobiotic model in interrogating the dynamic operations of commensal microbiota. Although this field is still at a very preliminary stage, whereby the functional properties of the complex gut microbiome remain less understood, several promising findings have been documented and exhibit great potential toward revolutionizing disease etiology and medical treatments. In this review, the interactions between gut microbiota and the host have been focused on, to provide an overview of the role of gut microbiota and their unique metabolites in conferring host protection against invading pathogen, regulation of diverse host physiological functions including metabolism, development and homeostasis of immunity and the nervous system. We elaborate on how gut microbial imbalance (dysbiosis) may lead to dysfunction of host machineries, thereby contributing to pathogenesis and/or progression toward a broad spectrum of diseases. Some of the most notable diseases namely Clostridium difficile infection (infectious disease), inflammatory bowel disease (intestinal immune-mediated disease), celiac disease (multisystemic autoimmune disorder), obesity (metabolic disease), colorectal cancer, and autism spectrum disorder (neuropsychiatric disorder) have been discussed and delineated along with recent findings. Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment. Toward the end of this review, several research gaps and limitations have been described along with suggested future studies to overcome the current research lacunae. Despite the ongoing debate on whether gut microbiome plays a role in the above-mentioned diseases, we have in this review, gathered evidence showing a potentially far more complex link beyond the unidirectional cause-and-effect relationship between them.
- 70Barnaba, V.; Sinigaglia, F. Molecular Mimicry and T Cell-Mediated Autoimmune Disease. J. Exp. Med. 1997, 185, 1529– 1531, DOI: 10.1084/jem.185.9.1529Google Scholar70https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXjtVOis7Y%253D&md5=fe3748156816316c57bccfdd853e0b86Molecular mimicry and T cell-mediated autoimmune diseaseBarnaba, Vincenzo; Sinigaglia, FrancescoJournal of Experimental Medicine (1997), 185 (9), 1529-1531CODEN: JEMEAV; ISSN:0022-1007. (Rockefeller University Press)A review and discussion with 29 refs. discussing the idea that mol. mimicry could account for the action and clonal expansion of autoreactive T-cells and the link between immune responses to infectious agents and autoimmunity.
- 71Bartlett, J. G. Antimicrobial Agents Implicated in Clostridium Difficile Toxin-Associated Diarrhea of Colitis. Johns Hopkins Med. J. 1981, 149, 6– 9Google Scholar71https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaL3M3ktlSqsw%253D%253D&md5=a3fc2f70ef652587b648504b3d2d63c4Antimicrobial agents implicated in Clostridium difficile toxin-associated diarrhea of colitisBartlett J GThe Johns Hopkins medical journal (1981), 149 (1), 6-9 ISSN:0021-7263.Records were reviewed for 329 patients who had antibiotic-associated diarrhea or colitis with stools showing a cytopathic toxin which is neutralized by Clostridium sordellii antitoxin. Previous studies indicate that the detection of this toxin implicate Clostridium difficile as the responsible pathogen. A spectrum of anatomical results in the colonic mucosa were found ranging from pseudomembranous colitis in 136 patients to an entirely normal endoscopic condition in 36 patients. The most frequently implicated agents were ampicillin, clindamycin, and cephalosporins. Collectively, these drugs accounted for approximately 80% of cases in which a single antimicrobial had been administered prior to the onset of symptoms. Analysis of data obtained in sequential time intervals showed a decline in the relative frequency of cases with use of clindamycin accompanied by an increase with use of cephalosporins. Less frequent drugs which were implicated in 3-8% of cases were, in rank order, penicillins other than ampicillin, erythromycin, sulfamethoxazole-trimethoprim and sulfasalazine. Tetracycline was the exclusive agent given to only three patients and there were no patients in whom chloramphenicol could be clearly implicated.
- 72Song, H. J.; Shim, K. N.; Jung, S. A.; Choi, H. J.; Lee, M. A.; Ryu, K. H.; Kim, S. E.; Yoo, K. Antibiotic-Associated Diarrhea: Candidate Organisms Other Than Clostridium Difficile. Korean J. Int. Med. 2008, 23, 9– 15, DOI: 10.3904/kjim.2008.23.1.9Google Scholar72https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1c3gsFGqsg%253D%253D&md5=16b10ea8ad28475eb2056bf702ad0548Antibiotic-associated diarrhea: candidate organisms other than Clostridium difficileSong Hyun Joo; Shim Ki-Nam; Jung Sung-Ae; Choi Hee Jung; Lee Mi Ae; Ryu Kum Hei; Kim Seong-Eun; Yoo KwonThe Korean journal of internal medicine (2008), 23 (1), 9-15 ISSN:1226-3303.BACKGROUND/AIMS: The direct toxic effects of antibiotics on the intestine can alter digestive functions and cause pathogenic bacterial overgrowth leading to antibiotic-associated diarrhea (AAD). Clostridium difficile (C. difficile) is widely known to be responsible for 10 approximately 20% of AAD cases. However, Klebsiella oxytoca, Clostridium perfringens, Staphylococcus aureus, and Candida species might also contribute to AAD. METHODS: We prospectively analyzed the organisms in stool and colon tissue cultures with a C. difficile toxin A assay in patients with AAD between May and December 2005. In addition, we performed the C. difficile toxin A assays using an enzyme-linked fluorescent assay technique. Patients were enrolled who had diarrhea with more than three stools per day for at least 2 days after the initiation of antibiotic treatment for up to 6 approximately 8 weeks after antibiotic discontinuation. RESULTS: Among 38 patients (mean age 59 +/- 18 years, M:F =18:20), the organism isolation rates were 28.9% (11/38) for stool culture, 18.4% (7/38) for colon tissue cultures and 13.2% (5/38) for the C. difficile toxin A assay. The overall rate of identification of organisms was 50.0% (19/38). Of the five patients that had a positive result by the C. difficile toxin A assay, two had no organism isolated by the stool or colon tissue culture. The organisms isolated from the stool cultures were C difficile (4), Klebsiella pneumoniae (K. pneumoniae) (3), Candida species (3), and Staphylococcus aureus (1). C. difficile (4) and K. pneumoniae (3) were isolated from the colon tissue culture. CONCLUSIONS: For C. difficile negative AAD patients, K. pneumoniae, Candida species and Staphylococcus aureus were found to be potential causative organisms.
- 73Pear, S. M.; Williamson, T. H.; Bettin, K. M.; Gerding, D. N.; Galgiani, J. N. Decrease in Nosocomial Clostridium Difficile-Associated Diarrhea by Restricting Clindamycin Use. Ann. Int. Med. 1994, 120, 272– 277, DOI: 10.7326/0003-4819-120-4-199402150-00003Google Scholar73https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaK2c7itFeqsg%253D%253D&md5=9883d5361f24f1e2df8f0f75bffd34d1Decrease in nosocomial Clostridium difficile-associated diarrhea by restricting clindamycin usePear S M; Williamson T H; Bettin K M; Gerding D N; Galgiani J NAnnals of internal medicine (1994), 120 (4), 272-7 ISSN:0003-4819.OBJECTIVE: To report the investigation and effective control of a nosocomial epidemic of Clostridium difficile-associated diarrhea. DESIGN: Concurrent surveillance for identification of new nosocomial cases, retrospective case-control analysis, and hospital formulary control of antibiotic use. SETTING: University-affiliated Veterans Affairs Medical Center located in southwestern United States. PATIENTS: Hospitalized patients who developed diarrhea submitted stool specimens for cytotoxin assay. Patients who were positive for cytotoxin were compared with control patients without infection. MEASUREMENTS: Isolates of C. difficile were typed by restriction endonuclease analysis. Antimicrobial agent use from hospital pharmacy records and selected patient data from chart review were correlated with frequency of specific laboratory abnormalities. RESULTS: For 13 months, the monthly incidence of C. difficile infection averaged more than five times that for the previous 21 months. Stool specimens from 34 patients (59%) contained a single strain (restriction enzyme analysis type J7). Clindamycin was statistically associated with the epidemic as shown by the following: clindamycin use at our center compared with national normal values, clindamycin use for years before compared with during the epidemic, monthly use of clindamycin compared with monthly frequency of infection, frequency of infection in patients receiving clindamycin compared with that in patients receiving other antimicrobial agents, and amount of clindamycin used by infected patients compared with that used by control patients. Restricting clindamycin use led to a prompt disease in infection rate and the type J7 organisms. CONCLUSION: A nosocomial epidemic of C. difficile diarrhea was controlled by analysis of antibiotic use patterns and by subsequent restriction of clindamycin.
- 74Lennard-Jones, J. E. Classification of Inflammatory Bowel Disease. Scand. J. Gastroenterol. 1989, 24, 2– 6, DOI: 10.3109/00365528909091339Google ScholarThere is no corresponding record for this reference.
- 75Nagao-Kitamoto, H.; Shreiner, A. B.; Gillilland, M. G., 3rd; Kitamoto, S.; Ishii, C.; Hirayama, A.; Kuffa, P.; El-Zaatari, M.; Grasberger, H.; Seekatz, A. M. Functional Characterization of Inflammatory Bowel Disease-Associated Gut Dysbiosis in Gnotobiotic Mice.. Cell Mol. Gastroenterol. Hepatol. 2016, 2, 468– 481, DOI: 10.1016/j.jcmgh.2016.02.003Google Scholar75https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2snhtFGisQ%253D%253D&md5=79d1444028ba5dd627402b1ee8eb8407Functional Characterization of Inflammatory Bowel Disease-Associated Gut Dysbiosis in Gnotobiotic MiceNagao-Kitamoto Hiroko; Shreiner Andrew B; Gillilland Merritt G 3rd; Kitamoto Sho; Kuffa Peter; El-Zaatari Mohamad; Grasberger Helmut; Higgins Peter D R; Kao John Y; Kamada Nobuhiko; Ishii Chiharu; Hirayama Akiyoshi; Fukuda Shinji; Seekatz Anna M; Young Vincent BCellular and molecular gastroenterology and hepatology (2016), 2 (4), 468-481 ISSN:2352-345X.BACKGROUND & AIMS: Gut dysbiosis is closely involved in the pathogenesis of inflammatory bowel disease (IBD). However, it remains unclear whether IBD-associated gut dysbiosis contributes to disease pathogenesis or is merely secondary to intestinal inflammation. We established a humanized gnotobiotic (hGB) mouse system to assess the functional role of gut dysbiosis associated with 2 types of IBD: Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Germ-free mice were colonized by the gut microbiota isolated from patients with CD and UC, and healthy controls. Microbiome analysis, bacterial functional gene analysis, luminal metabolome analysis, and host gene expression analysis were performed in hGB mice. Moreover, the colitogenic capacity of IBD-associated microbiota was evaluated by colonizing germ-free colitis-prone interleukin 10-deficient mice with dysbiotic patients' microbiota. RESULTS: Although the microbial composition seen in donor patients' microbiota was not completely reproduced in hGB mice, some dysbiotic features of the CD and UC microbiota (eg, decreased diversity, alteration of bacterial metabolic functions) were recapitulated in hGB mice, suggesting that microbial community alterations, characteristic for IBD, can be reproduced in hGB mice. In addition, colonization by the IBD-associated microbiota induced a proinflammatory gene expression profile in the gut that resembles the immunologic signatures found in CD patients. Furthermore, CD microbiota triggered more severe colitis than healthy control microbiota when colonized in germ-free interleukin 10-deficient mice. CONCLUSIONS: Dysbiosis potentially contributes to the pathogenesis of IBD by augmenting host proinflammatory immune responses. Transcript profiling: GSE73882.
- 76Sokol, H.; Pigneur, B.; Watterlot, L.; Lakhdari, O.; Bermudez-Humaran, L. G.; Gratadoux, J. J.; Blugeon, S.; Bridonneau, C.; Furet, J. P.; Corthier, G. Faecalibacterium Prausnitzii Is an Anti-Inflammatory Commensal Bacterium Identified by Gut Microbiota Analysis of Crohn Disease Patients. Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 16731– 16736, DOI: 10.1073/pnas.0804812105Google Scholar76https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhtleks7%252FI&md5=0a6676854a1ad91844fed38ac61ec360Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patientsSokol, Harry; Pigneur, Benedicte; Watterlot, Laurie; Lakhdari, Omar; Bermudez-Humarian, Luis G.; Gratadoux, Jean-Jacques; Blugeon, Sebastien; Bridonneau, Chantal; Furet, Jean-Pierre; Corthier, Gerard; Grangette, Corinne; Vasquez, Nadia; Pochart, Philippe; Trugnan, Germain; Thomas, Ginette; Blottiere, Herve M.; Dore, Joel; Marteau, Philippe; Seksik, Philippe; Langella, PhilippeProceedings of the National Academy of Sciences of the United States of America (2008), 105 (43), 16731-16736CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)A decrease in the abundance and biodiversity of intestinal bacteria within the dominant phylum Firmicutes has been obsd. repeatedly in Crohn disease (CD) patients. In this study, we detd. the compn. of the mucosa-assocd. microbiota of CD patients at the time of surgical resection and 6 mo later using FISH anal. We found that a redn. of a major member of Firmicutes, Faecalibacterium prausnitzii, is assocd. with a higher risk of postoperative recurrence of ileal CD. A lower proportion of F. prausnitzii on resected ileal Crohn mucosa also was assocd. with endoscopic recurrence at 6 mo. To evaluate the immunomodulatory properties of F. prausnitzii we analyzed the anti-inflammatory effects of F. prausnitzii in both in vitro (cellular models) and in vivo [2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced] colitis in mice. In Caco-2 cells transfected with a reporter gene for NF-κB activity, F. prausnitzii had no effect on IL-1β-induced NF-κB activity, whereas the supernatant abolished it. In vitro peripheral blood mononuclear cell stimulation by F. prausnitzii led to significantly lower IL-12 and IFN-γ prodn. levels and higher secretion of IL-10. Oral administration of either live F. prausnitzii or its supernatant markedly reduced the severity of TNBS colitis and tended to correct the dysbiosis assocd. with TNBS colitis, as demonstrated by real-time quant. PCR (qPCR) anal. F. prausnitzii exhibits anti-inflammatory effects on cellular and TNBS colitis models, partly due to secreted metabolites able to block NF-κB activation and IL-8 prodn. These results suggest that counterbalancing dysbiosis using F. prausnitzii as a probiotic is a promising strategy in CD treatment.
- 77Willing, B. P.; Dicksved, J.; Halfvarson, J.; Andersson, A. F.; Lucio, M.; Zheng, Z.; Jarnerot, G.; Tysk, C.; Jansson, J. K.; Engstrand, L. A Pyrosequencing Study in Twins Shows That Gastrointestinal Microbial Profiles Vary with Inflammatory Bowel Disease Phenotypes. Gastroenterology 2010, 139, 1844– 1854, DOI: 10.1053/j.gastro.2010.08.049Google Scholar77https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3M%252FhtFSitg%253D%253D&md5=dbb5499b9ed56a6e7ff91638b3f8621eA pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypesWilling Ben P; Dicksved Johan; Halfvarson Jonas; Andersson Anders F; Lucio Marianna; Zheng Zongli; Jarnerot Gunnar; Tysk Curt; Jansson Janet K; Engstrand LarsGastroenterology (2010), 139 (6), 1844-1854.e1 ISSN:.BACKGROUND & AIMS: The composition of the gastrointestinal microbiota is thought to have an important role in the etiology of inflammatory bowel diseases (IBDs) such as Crohn's disease (CD) and ulcerative colitis (UC). Interindividual variation and an inability to detect less abundant bacteria have made it difficult to correlate specific bacteria with disease. METHODS: We used 454 pyrotag sequencing to determine the compositions of microbial communities in feces samples collected from a cohort of 40 twin pairs who were concordant or discordant for CD or UC, and in mucosal samples from a subset of the cohort. The cohort primarily comprised patients who were in remission, but also some with active disease. RESULTS: The profiles of the microbial community differed with disease phenotypes; relative amounts of bacterial populations correlated with IBD phenotypes. The microbial compositions of individuals with CD differed from those of healthy individuals, but were similar between healthy individuals and individuals with UC. Profiles from individuals with CD that predominantly involved the ileum differed from those with CD that predominantly involved the colon; several bacterial populations increased or decreased with disease type. Changes specific to patients with ileal CD included the disappearance of core bacteria, such as Faecalibacterium and Roseburia, and increased amounts of Enterobacteriaceae and Ruminococcus gnavus. CONCLUSIONS: Bacterial populations differ in abundance among individuals with different phenotypes of CD. Specific species of bacteria are associated with ileal CD; further studies should investigate their role in pathogenesis.
- 78Machiels, K.; Joossens, M.; Sabino, J.; De Preter, V.; Arijs, I.; Eeckhaut, V.; Ballet, V.; Claes, K.; Van Immerseel, F.; Verbeke, K. A Decrease of the Butyrate-Producing Species Roseburia Hominis and Faecalibacterium Prausnitzii Defines Dysbiosis in Patients with Ulcerative Colitis. Gut 2014, 63, 1275– 1283, DOI: 10.1136/gutjnl-2013-304833Google Scholar78https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFGhur3E&md5=17f9deeb98db4f33aa709685063073deA decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitisMachiels, Kathleen; Joossens, Marie; Sabino, Joao; De Preter, Vicky; Arijs, Ingrid; Eeckhaut, Venessa; Ballet, Vera; Claes, Karolien; Van Immerseel, Filip; Verbeke, Kristin; Ferrante, Marc; Verhaegen, Jan; Rutgeerts, Paul; Vermeire, SeverineGut (2014), 63 (8), 1275-1283CODEN: GUTTAK; ISSN:0017-5749. (BMJ Publishing Group)Objective Bacteria play an important role in the onset and perpetuation of intestinal inflammation in inflammatory bowel disease (IBD). Unlike in Crohn's disease (CD), in which dysbiosis has been better characterised, in ulcerative colitis (UC), only small cohorts have been studied and showed conflicting data. Therefore, we evaluated in a large cohort if the microbial signature described in CD is also present in UC, and if we could characterize predominant dysbiosis in UC. To assess the functional impact of dysbiosis, we quantified the bacterial metabolites. Design The predominant microbiota from 127 UC patients and 87 age and sex-matched controls was analyzed using denaturing gradient gel electrophoresis (DGGE) anal. Differences were quant. validated using real-time PCR. Metabolites were quantified using gas chromatog.-mass spectrometry. Results Based on DGGE anal., the microbial signature previously described in CD was not present in UC. Real-time PCR anal. revealed a lower abundance of Roseburia hominis (p<0.0001) and Faecalibacterium prausnitzii (p<0.0001) in UC patients compared to controls. Both species showed an inverse correlation with disease activity. Short-chain fatty acids (SCFA) were reduced in UC patients (p=0.014), but no direct correlation between SCFA and the identified bacteria was found. Conclusions The compn. of the fecal microbiota of UC patients differs from that of healthy individuals: we found a redn. in R hominis and F prausnitzii, both well-known butyrate-producing bacteria of the Firmicutes phylum. These results underscore the importance of dysbiosis in IBD but suggest that different bacterial species contribute to the pathogenesis of UC and CD.
- 79Peng, L.; He, Z.; Chen, W.; Holzman, I. R.; Lin, J. Effects of Butyrate on Intestinal Barrier Function in a Caco-2 Cell Monolayer Model of Intestinal Barrier. Pediatr. Res. 2007, 61, 37– 41, DOI: 10.1203/01.pdr.0000250014.92242.f3Google Scholar79https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2s%252FhsFWitw%253D%253D&md5=85ec6f2e610f8838957e528ceada2889Effects of butyrate on intestinal barrier function in a Caco-2 cell monolayer model of intestinal barrierPeng Luying; He Zhenjuan; Chen Wei; Holzman Ian R; Lin JingPediatric research (2007), 61 (1), 37-41 ISSN:0031-3998.Production of short-chain fatty acids (SCFA) in the intestinal lumen may play an important role in the maintenance of the intestinal barrier. However, overproduction/accumulation of SCFA in the bowel may be toxic to the intestinal mucosa and has been hypothesized to play a role in the pathogenesis of neonatal necrotizing enterocolitis (NEC). By using a Caco-2 cell monolayer model of intestinal barrier, we report here that the effect of butyrate on the intestinal barrier is paradoxical. Butyrate at a low concentration (2 mM) promotes intestinal barrier function as measured by a significant increase in transepithelial electrical resistance (TER) and a significant decrease in inulin permeability. Butyrate at a high concentration (8 mM) reduces TER and increases inulin permeability significantly. Butyrate induces apoptosis and reduces the number of viable Caco-2 cells in a dose-dependent manner. Intestinal barrier function impairment induced by high concentrations of butyrate is most likely related to butyrate-induced cytotoxicity due to apoptosis. We conclude that the effect of butyrate on the intestinal barrier is paradoxical; i.e. whereas low concentrations of butyrate may be beneficial in promoting intestinal barrier function, excessive butyrate may induce severe intestinal epithelial cell apoptosis and disrupt intestinal barrier.
- 80Carroll, I. M.; Chang, Y. H.; Park, J.; Sartor, R. B.; Ringel, Y. Luminal and Mucosal-Associated Intestinal Microbiota in Patients with Diarrhea-Predominant Irritable Bowel Syndrome. Gut Pathog. 2010, 2, 19, DOI: 10.1186/1757-4749-2-19Google Scholar80https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3M7gt1SksA%253D%253D&md5=4dc4e3998f9d57e2016d47910797ece5Luminal and mucosal-associated intestinal microbiota in patients with diarrhea-predominant irritable bowel syndromeCarroll Ian M; Chang Young-Hyo; Park Jiwon; Sartor R Balfour; Ringel YehudaGut pathogens (2010), 2 (1), 19 ISSN:.BACKGROUND: Recent studies have suggested a role for an altered intestinal microbiota in the pathophysiology of irritable bowel syndrome (IBS). However, no consensus has been reached regarding the association between specific enteric bacterial groups and IBS. The aim of this study was to investigate the fecal and mucosal-associated microbiota using two independent techniques in intestinal samples from diarrhea-predominant IBS (D-IBS) and healthy controls. METHODS: Fecal and colonic mucosal biopsy samples were obtained from 10 D-IBS patients and 10 healthy controls. Colonic tissue was collected during a un-sedated un-prepped flexible sigmoidoscopy. Fecal and tissue samples were processed immediately upon collection for culture under aerobic and anaerobic conditions or frozen for further molecular analysis. DNA was extracted from all frozen samples and used to enumerate specific bacterial groups using quantitative real-time PCR (qPCR). RESULTS: Culture analysis of intestinal samples demonstrated a significant reduction in the concentration of aerobic bacteria in fecal samples from D-IBS patients when compared to healthy controls (1.4 × 107 vs. 8.4 × 108 CFUs/g feces, P = 0.002). qPCR analysis demonstrated a significant 3.6 fold increase (P = 0.02) in concentrations of fecal Lactobacillus species between D-IBS patients and healthy controls. CONCLUSIONS: Our culture and molecular data indicate that quantitative differences exist in specific bacterial groups in the microbiota between D-IBS and healthy subjects.
- 81Bhattarai, Y.; Muniz Pedrogo, D. A.; Kashyap, P. C. Irritable Bowel Syndrome: A Gut Microbiota-Related Disorder?. Am. J. Physiol. Gastrointest. Liver Physiol. 2017, 312, G52– G62, DOI: 10.1152/ajpgi.00338.2016Google ScholarThere is no corresponding record for this reference.
- 82Salonen, A.; de Vos, W. M.; Palva, A. Gastrointestinal Microbiota in Irritable Bowel Syndrome: Present State and Perspectives. Microbiology 2010, 156, 3205– 3215, DOI: 10.1099/mic.0.043257-0Google Scholar82https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsFCiur3E&md5=724a75492d2ba6de26f39a3352eb8915Gastrointestinal microbiota in irritable bowel syndrome: present state and perspectivesSalonen, Anne; de Vos, Willem M.; Palva, AiriMicrobiology (Reading, United Kingdom) (2010), 156 (11), 3205-3215CODEN: MROBEO; ISSN:1350-0872. (Society for General Microbiology)Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that has been assocd. with aberrant microbiota. This review focuses on the recent mol. insights generated by analyzing the intestinal microbiota in subjects suffering from IBS. Special emphasis is given to studies that compare and contrast the microbiota of healthy subjects with that of IBS patients classified into different subgroups based on their predominant bowel pattern as defined by the Rome criteria. The current data available from a limited no. of patients do not reveal pronounced and reproducible IBS-related deviations of entire phylogenetic or functional microbial groups, but rather support the concept that IBS patients have alterations in the proportions of commensals with interrelated changes in the metabolic output and overall microbial ecol. The lack of apparent similarities in the taxonomy of microbiota in IBS patients may partially arise from the fact that the applied mol. methods, the nature and location of IBS subjects, and the statistical power of the studies have varied considerably. Most recent advances, esp. the finding that several uncharacterized phylotypes show non-random segregation between healthy and IBS subjects, indicate the possibility of discovering bacteria specific for IBS. Moreover, tools are being developed for the functional anal. of the relationship between the intestinal microbiota and IBS. These approaches may be instrumental in the evaluation of the ecol. dysbiosis hypothesis in the gut ecosystem. Finally, we discuss the future outlook for research avenues and candidate microbial biomarkers that may eventually be used in IBS diagnosis.
- 83Greenblum, S.; Turnbaugh, P. J.; Borenstein, E. Metagenomic Systems Biology of the Human Gut Microbiome Reveals Topological Shifts Associated with Obesity and Inflammatory Bowel Disease. Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 594– 599, DOI: 10.1073/pnas.1116053109Google Scholar83https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xht1ensbc%253D&md5=f52c717473ee433912f8a7b591c5aee6Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel diseaseGreenblum, Sharon; Turnbaugh, Peter J.; Borenstein, ElhananProceedings of the National Academy of Sciences of the United States of America (2012), 109 (2), 594-599, S594/1-S594/31CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)The human microbiome plays a key role in a wide range of host-related processes and has a profound effect on human health. Comparative analyses of the human microbiome have revealed substantial variation in species and gene compn. assocd. with a variety of disease states but may fall short of providing a comprehensive understanding of the impact of this variation on the community and on the host. Here, we introduce a metagenomic systems biol. computational framework, integrating metagenomic data with an in silico systems-level anal. of metabolic networks. Focusing on the gut microbiome, we analyze fecal metagenomic data from 124 unrelated individuals, as well as six monozygotic twin pairs and their mothers, and generate community-level metabolic networks of the microbiome. Placing variations in gene abundance in the context of these networks, we identify both gene-level and network-level topol. differences assocd. with obesity and inflammatory bowel disease (IBD). We show that genes assocd. with either of these host states tend to be located at the periphery of the metabolic network and are enriched for topol. derived metabolic "inputs." These findings may indicate that lean and obese microbiomes differ primarily in their interface with the host and in the way they interact with host metab. We further demonstrate that obese microbiomes are less modular, a hallmark of adaptation to low-diversity environments. We addnl. link these topol. variations to community species compn. The system-level approach presented here lays the foundation for a unique framework for studying the human microbiome, its organization, and its impact on human health.
- 84Schloissnig, S.; Arumugam, M.; Sunagawa, S.; Mitreva, M.; Tap, J.; Zhu, A.; Waller, A.; Mende, D. R.; Kultima, J. R.; Martin, J. Genomic Variation Landscape of the Human Gut Microbiome. Nature 2013, 493, 45– 50, DOI: 10.1038/nature11711Google Scholar84https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3s7pvVGhtg%253D%253D&md5=3f9ae915314efb7bdfe23ebfb6fd7033Genomic variation landscape of the human gut microbiomeSchloissnig Siegfried; Arumugam Manimozhiyan; Sunagawa Shinichi; Mitreva Makedonka; Tap Julien; Zhu Ana; Waller Alison; Mende Daniel R; Kultima Jens Roat; Martin John; Kota Karthik; Sunyaev Shamil R; Weinstock George M; Bork PeerNature (2013), 493 (7430), 45-50 ISSN:.Whereas large-scale efforts have rapidly advanced the understanding and practical impact of human genomic variation, the practical impact of variation is largely unexplored in the human microbiome. We therefore developed a framework for metagenomic variation analysis and applied it to 252 faecal metagenomes of 207 individuals from Europe and North America. Using 7.4 billion reads aligned to 101 reference species, we detected 10.3 million single nucleotide polymorphisms (SNPs), 107,991 short insertions/deletions, and 1,051 structural variants. The average ratio of non-synonymous to synonymous polymorphism rates of 0.11 was more variable between gut microbial species than across human hosts. Subjects sampled at varying time intervals exhibited individuality and temporal stability of SNP variation patterns, despite considerable composition changes of their gut microbiota. This indicates that individual-specific strains are not easily replaced and that an individual might have a unique metagenomic genotype, which may be exploitable for personalized diet or drug intake.
- 85Faith, J. J.; Guruge, J. L.; Charbonneau, M.; Subramanian, S.; Seedorf, H.; Goodman, A. L.; Clemente, J. C.; Knight, R.; Heath, A. C.; Leibel, R. L. The Long-Term Stability of the Human Gut Microbiota. Science 2013, 341, 1237439, DOI: 10.1126/science.1237439Google Scholar85https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3sjotlOqtQ%253D%253D&md5=4125d5f4f2b7917f39f92d801a3c95deThe long-term stability of the human gut microbiotaFaith Jeremiah J; Guruge Janaki L; Charbonneau Mark; Subramanian Sathish; Seedorf Henning; Goodman Andrew L; Clemente Jose C; Knight Rob; Heath Andrew C; Leibel Rudolph L; Rosenbaum Michael; Gordon Jeffrey IScience (New York, N.Y.) (2013), 341 (6141), 1237439 ISSN:.A low-error 16S ribosomal RNA amplicon sequencing method, in combination with whole-genome sequencing of >500 cultured isolates, was used to characterize bacterial strain composition in the fecal microbiota of 37 U.S. adults sampled for up to 5 years. Microbiota stability followed a power-law function, which when extrapolated suggests that most strains in an individual are residents for decades. Shared strains were recovered from family members but not from unrelated individuals. Sampling of individuals who consumed a monotonous liquid diet for up to 32 weeks indicated that changes in strain composition were better predicted by changes in weight than by differences in sampling interval. This combination of stability and responsiveness to physiologic change confirms the potential of the gut microbiota as a diagnostic tool and therapeutic target.
- 86Yan, M.; Pamp, S. J.; Fukuyama, J.; Hwang, P. H.; Cho, D. Y.; Holmes, S.; Relman, D. A. Nasal Microenvironments and Interspecific Interactions Influence Nasal Microbiota Complexity and S. Aureus Carriage. Cell Host Microbe 2013, 14, 631– 640, DOI: 10.1016/j.chom.2013.11.005Google Scholar86https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFylt7fO&md5=569a39a2f6a03855b949a31506b73397Nasal Microenvironments and Interspecific Interactions Influence Nasal Microbiota Complexity and S. aureus CarriageYan, Miling; Pamp, Sunje J.; Fukuyama, Julia; Hwang, Peter H.; Cho, Do-Yeon; Holmes, Susan; Relman, David A.Cell Host & Microbe (2013), 14 (6), 631-640CODEN: CHMECB; ISSN:1931-3128. (Elsevier Inc.)The indigenous microbiota of the nasal cavity plays important roles in human health and disease. Patterns of spatial variation in microbiota compn. may help explain Staphylococcus aureus colonization and reveal interspecies and species-host interactions. To assess the biogeog. of the nasal microbiota, we sampled healthy subjects, representing both S. aureus carriers and noncarriers at three nasal sites (anterior naris, middle meatus, and sphenoethmoidal recess). Phylogenetic compositional and sparse linear discriminant analyses revealed communities that differed according to site epithelium type and S. aureus culture-based carriage status. Corynebacterium accolens and C. pseudodiphtheriticum were identified as the most important microbial community determinants of S. aureus carriage, and competitive interactions were only evident at sites with ciliated pseudostratified columnar epithelium. In vitro cocultivation expts. provided supporting evidence of interactions among these species. These results highlight spatial variation in nasal microbial communities and differences in community compn. between S. aureus carriers and noncarriers.
- 87Biswas, K.; Hoggard, M.; Jain, R.; Taylor, M. W.; Douglas, R. G. The Nasal Microbiota in Health and Disease: Variation within and between Subjects. Front. Microbiol. 2015, 9, 134, DOI: 10.3389/fmicb.2015.00134Google Scholar87https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2Mnls1anuw%253D%253D&md5=34c7afde2ac732d0969c7b06226f0e76The nasal microbiota in health and disease: variation within and between subjectsBiswas Kristi; Jain Ravi; Douglas Richard G; Hoggard Michael; Taylor Michael WFrontiers in microbiology (2015), 9 (), 134 ISSN:1664-302X.Chronic rhinosinusitis (CRS) affects approximately 5% of the adult population in Western societies and severely reduces the patient's quality of life. The role of bacteria in the pathogenesis of this condition has not yet been established with certainty. However, recent reports of bacterial and fungal biofilms in CRS highlight a potential role for these microorganisms. In this study, 16S rRNA gene-targeted amplicon pyrosequencing and qPCR were used to determine the composition and abundance, respectively, of the sinus microbiota within 9 patients with CRS and 6 healthy individuals. Within-patient variability was also investigated by sampling from anterior nares, inferior turbinate, and middle meatus on each side of the sinuses. Our results indicate that more of the variation in bacterial composition can be explained by inter-personal differences, rather than sampling location or even disease status. In addition, bacterial community diversity was significantly lower in CRS samples compared to those from healthy subjects, whereas bacterial load was not associated with disease status. Although members of the genera Corynebacterium and Staphylococcus were prevalent in the majority of samples (including healthy subjects), the large amount of variation observed between individuals, particularly within the CRS cohort, suggests that an imbalance or dysbiosis in community structure could be the driving force behind the disease. Ultimately, understanding the causes of variation within the sinus microbiota may lead to more personalized treatment options for CRS.
- 88Bassis, C. M.; Tang, A. L.; Young, V. B.; Pynnonen, M. A. The Nasal Cavity Microbiota of Healthy Adults. Microbiome 2014, 2, 27, DOI: 10.1186/2049-2618-2-27Google Scholar88https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2M%252FjvFaltg%253D%253D&md5=47ef2c698e408d23efee6768dce8edf8The nasal cavity microbiota of healthy adultsBassis Christine M; Young Vincent B; Tang Alice L; Pynnonen Melissa AMicrobiome (2014), 2 (), 27 ISSN:2049-2618.BACKGROUND: The microbiota of the nares has been widely studied. However, relatively few studies have investigated the microbiota of the nasal cavity posterior to the nares. This distinct environment has the potential to contain a distinct microbiota and play an important role in health. RESULTS: We obtained 35,142 high-quality bacterial 16S rRNA-encoding gene sequence reads from the nasal cavity and oral cavity (the dorsum of the tongue and the buccal mucosa) of 12 healthy adult humans and deposited these data in the Sequence Read Archive (SRA) of the National Center for Biotechnology Information (NCBI) (Bioproject: PRJNA248297). In our initial analysis, we compared the bacterial communities of the nasal cavity and the oral cavity from ten of these subjects. The nasal cavity bacterial communities were dominated by Actinobacteria, Firmicutes, and Proteobacteria and were statistically distinct from those on the tongue and buccal mucosa. For example, the same Staphylococcaceae operational taxonomic unit (OTU) was present in all of the nasal cavity samples, comprising up to 55% of the community, but Staphylococcaceae was comparatively uncommon in the oral cavity. CONCLUSIONS: There are clear differences between nasal cavity microbiota and oral cavity microbiota in healthy adults. This study expands our knowledge of the nasal cavity microbiota and the relationship between the microbiota of the nasal and oral cavities.
- 89Zhou, Y.; Mihindukulasuriya, K. A.; Gao, H.; La Rosa, P. S.; Wylie, K. M.; Martin, J. C.; Kota, K.; Shannon, W. D.; Mitreva, M.; Sodergren, E. Exploration of Bacterial Community Classes in Major Human Habitats. Genome Biol. 2014, 15, R66, DOI: 10.1186/gb-2014-15-5-r66Google ScholarThere is no corresponding record for this reference.
- 90Ramakrishnan, V. R.; Feazel, L. M.; Gitomer, S. A.; Ir, D.; Robertson, C. E.; Frank, D. N. The Microbiome of the Middle Meatus in Healthy Adults. PLoS One 2013, 8, e85507, DOI: 10.1371/journal.pone.0085507Google Scholar90https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXisFGntbs%253D&md5=292a85e98152b365f633e1aec224d2dbThe microbiome of the middle meatus in healthy adultsRamakrishnan, Vijay R.; Feazel, Leah M.; Gitomer, Sarah A.; Ir, Diana; Robertson, Charles E.; Frank, Daniel N.PLoS One (2013), 8 (12), e85507/1-e85507/10, 10 pp.CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)Rhinitis and rhinosinusitis are multifactorial disease processes in which bacteria may play a role either in infection or stimulation of the inflammatory process. Rhinosinusitis has been historically studied with culture-based techniques, which have implicated several common pathogens in disease states. More recently, the NIH Human Microbiome Project has examd. the microbiome at a no. of accessible body sites, and demonstrated differences among healthy and diseased patients. Recent DNA-based sinus studies have suggested that healthy sinuses are not sterile, as was previously believed, but the normal sinonasal microbiome has yet to be thoroughly examd. Middle meatus swab specimens were collected from 28 consecutive patients presenting with no signs or symptoms of rhinosinusitis. Bacterial colonization was assessed in these specimens using quant. PCR and 16S rRNA pyrosequencing. All subjects were pos. for bacterial colonization of the middle meatus. Staphylococcus aureus, Staphylococcus epidermidis and Propionibacterium acnes were the most prevalent and abundant microorganisms detected. Rich and diverse bacterial assemblages are present in the sinonasal cavity in the normal state, including opportunistic pathogens typically found in the nasopharynx. This work helps establish a baseline for understanding how the sinonasal microbiome may impact diseases of the upper airways.
- 91Zhang, Z.; Adappa, N. D.; Doghramji, L. J.; Chiu, A. G.; Cohen, N. A.; Palmer, J. N. Different Clinical Factors Associated with Staphylococcus Aureus and Pseudomonas Aeruginosa in Chronic Rhinosinusitis. Int. Forum Allergy. Rhinol. 2015, 5, 724– 733, DOI: 10.1002/alr.21532Google Scholar91https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2Mjms1Khtg%253D%253D&md5=9f87ce97e36812e21321f96196e177c8Different clinical factors associated with Staphylococcus aureus and Pseudomonas aeruginosa in chronic rhinosinusitisZhang Zi; Adappa Nithin D; Doghramji Laurel J; Cohen Noam A; Palmer James N; Chiu Alexander G; Cohen Noam AInternational forum of allergy & rhinology (2015), 5 (8), 724-33 ISSN:.BACKGROUND: Staphylococcus aureus and Pseudomonas aeruginosa are common culture isolates in chronic rhinosinusitis (CRS). We aimed to determine whether they were associated with different clinical factors of CRS. METHODS: Adult CRS patients who underwent functional endoscopic sinus surgery (FESS) between October 1, 2007 and December 31, 2011 were recruited. Patient demographics, Lund-Mackay computed tomography (CT) scores, 22-item Sino-Nasal Outcome Test (SNOT-22) scores, disease characteristics, and medication use were collected prior to FESS. Intraoperative culture was obtained in a standard manner. We compared patients with isolates of S. aureus or P. aeruginosa to patients with other culture results and no bacterial growth, respectively. Multivariate logistic regression was performed. RESULTS: A total of 376 patients met criteria; 104 patients (28%) had S. aureus, 32 (9%) had P. aeruginosa, and 10 patients (3%) had no bacterial growth. After adjusting for all clinical factors, compared to patients with positive culture other than S. aureus, patients with S. aureus had 1.9 times increased odds of having nasal polyps (odds ratio [OR] = 1.9; 95% confidence interval [CI], 1.0 to 3.3; p = 0.036); when compared to patients with positive culture other than P. aeruginosa, patients with P. aeruginosa had 7.8 times increased odds of having prior FESS (OR = 7.8; 95% CI, 2.1 to 28.9; p = 0.002) (91% vs 58%; p < 0.001) and 3.6 times increased odds of having diabetes with marginal significance (OR = 3.6; 95% CI, 1.0 to 13.2; p = 0.053). The sample size in the no bacterial growth group was too small to draw firm conclusions. CONCLUSION: S. aureus was more common in CRS patients with nasal polyps, whereas P. aeruginosa was more common in CRS patients with prior FESS history and possibly diabetes.
- 92Abreu, N. A.; Nagalingam, N. A.; Song, Y.; Roediger, F. C.; Pletcher, S. D.; Goldberg, A. N.; Lynch, S. V. Sinus Microbiome Diversity Depletion and Corynebacterium Tuberculostearicum Enrichment Mediates Rhinosinusitis. Sci. Transl. Med. 2012, 4, 151ra124, DOI: 10.1126/scitranslmed.3003783Google ScholarThere is no corresponding record for this reference.
- 93Huang, Y. J.; Nelson, C. E.; Brodie, E. L.; DeSantis, T. Z.; Baek, M. S.; Liu, J.; Woyke, T.; Allgaier, M.; Bristow, J.; Wiener-Kronish, J. P. Airway Microbiota and Bronchial Hyperresponsiveness in Patients with Suboptimally Controlled Asthma. J. Allergy Clin. Immunol. 2011, 127, 372– 381, DOI: 10.1016/j.jaci.2010.10.048Google Scholar93https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3M7ls1ensA%253D%253D&md5=9e40905ef003efa21ffee87e416cd84eAirway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthmaHuang Yvonne J; Nelson Craig E; Brodie Eoin L; Desantis Todd Z; Baek Marshall S; Liu Jane; Woyke Tanja; Allgaier Martin; Bristow Jim; Wiener-Kronish Jeanine P; Sutherland E Rand; King Tonya S; Icitovic Nikolina; Martin Richard J; Calhoun William J; Castro Mario; Denlinger Loren C; Dimango Emily; Kraft Monica; Peters Stephen P; Wasserman Stephen I; Wechsler Michael E; Boushey Homer A; Lynch Susan VThe Journal of allergy and clinical immunology (2011), 127 (2), 372-381.e1-3 ISSN:.BACKGROUND: Improvement in lung function after macrolide antibiotic therapy has been attributed to reduction in bronchial infection by specific bacteria. However, the airway might be populated by a more diverse microbiota, and clinical features of asthma might be associated with characteristics of the airway microbiota present. OBJECTIVE: We sought to determine whether relationships exist between the composition of the airway bacterial microbiota and clinical features of asthma using culture-independent tools capable of detecting the presence and relative abundance of most known bacteria. METHODS: In this pilot study bronchial epithelial brushings were collected from 65 adults with suboptimally controlled asthma participating in a multicenter study of the effects of clarithromycin on asthma control and 10 healthy control subjects. A combination of high-density 16S ribosomal RNA microarray and parallel clone library-sequencing analysis was used to profile the microbiota and examine relationships with clinical measurements. RESULTS: Compared with control subjects, 16S ribosomal RNA amplicon concentrations (a proxy for bacterial burden) and bacterial diversity were significantly higher among asthmatic patients. In multivariate analyses airway microbiota composition and diversity were significantly correlated with bronchial hyperresponsiveness. Specifically, the relative abundance of particular phylotypes, including members of the Comamonadaceae, Sphingomonadaceae, Oxalobacteraceae, and other bacterial families were highly correlated with the degree of bronchial hyperresponsiveness. CONCLUSION: The composition of bronchial airway microbiota is associated with the degree of bronchial hyperresponsiveness among patients with suboptimally controlled asthma. These findings support the need for further functional studies to examine the potential contribution of members of the airway microbiota in asthma pathogenesis.
- 94Marri, P. R.; Stern, D. A.; Wright, A. L.; Billheimer, D.; Martinez, F. D. Asthma-Associated Differences in Microbial Composition of Induced Sputum. J. Allergy Clin. Immunol. 2013, 131, 346– 352, DOI: 10.1016/j.jaci.2012.11.013Google Scholar94https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhvFWhsLrP&md5=497b8615868d1a162aa38a8cbb8af1b2Asthma-associated differences in microbial composition of induced sputumMarri, Pradeep Reddy; Stern, Debra A.; Wright, Anne L.; Billheimer, Dean; Martinez, Fernando D.Journal of Allergy and Clinical Immunology (2013), 131 (2), 346-352.e3CODEN: JACIBY; ISSN:0091-6749. (Elsevier)It is increasingly evident that microbial colonization of the respiratory tract might have a role in the pathogenesis of asthma. We sought to characterize and compare the microbiome of induced sputum in asthmatic and nonasthmatic adults. Induced sputum samples were obtained from 10 nonasthmatic subjects and 10 patients with mild active asthma (8/10 were not using inhaled corticosteroids). Total DNA was extd. from sputum supernatants and amplified by using primers specific for the V6 hypervariable region of bacterial 16s rRNA. Samples were barcoded, and equimolar concns. of 20 samples were pooled and sequenced with the 454 GS FLX sequencer. Sequences were assigned to bacterial taxa by comparing them with 16s rRNA sequences in the Ribosomal Database Project. All sputum samples contained 5 major bacterial phyla: Firmicutes, Proteobacteria, Actinobacteria, Fusobacterium, and Bacteroidetes, with the first 3 phyla accounting for more than 90% of the total sequences. Proteobacteria were present in higher proportions in asthmatic patients (37% vs 15%, P < .001). In contrast, Firmicutes (47% vs 63%, P = .17) and Actinobacteria (10% vs 14%, P = .36) were found more frequently in samples from nonasthmatic subjects, although this was not statistically significant. Hierarchical clustering produced 2 significant clusters: one contained primarily asthmatic samples and the second contained primarily nonasthmatic samples. In addn., samples from asthmatic patients had greater bacterial diversity compared with samples from nonasthmatic subjects. Patients with mild asthma have an altered microbial compn. in the respiratory tract that is similar to that obsd. in patients with more severe asthma.
- 95Bisgaard, H.; Hermansen, M. N.; Buchvald, F.; Loland, L.; Halkjaer, L. B.; Bonnelykke, K.; Brasholt, M.; Heltberg, A.; Vissing, N. H.; Thorsen, S. V. Childhood Asthma after Bacterial Colonization of the Airway in Neonates. N. Engl. J. Med. 2007, 357, 1487– 1495, DOI: 10.1056/NEJMoa052632Google Scholar95https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtFKmurzK&md5=ce113c6a68c65b43eee9871e71b92780Childhood asthma after bacterial colonization of the airway in neonatesBisgaard, Hans; Northman Hermansen, Mette; Buchvald, Frederik; Loland, Lotte; Brydensholt Halkjaer, Liselotte; Boennelykke, Klaus; Brasholt, Martin; Heltberg, Andreas; Hawwa Vissing, Nadja; Vester Thorsen, Sannie; Stage, Malene; Bressen Pipper, ChristianNew England Journal of Medicine (2007), 357 (15), 1487-1495CODEN: NEJMAG; ISSN:0028-4793. (Massachusetts Medical Society)BACKGROUND Pathol. features of the airway in young children with severe recurrent wheeze suggest an assocn. between bacterial colonization and the initiating events of early asthma. We conducted a study to investigate a possible assocn. between bacterial colonization of the hypopharynx in asymptomatic neonates and later development of recurrent wheeze, asthma, and allergy during the first 5 years of life. METHODS The subjects were children from the Copenhagen Prospective Study on Asthma in Childhood birth cohort who were born to mothers with asthma. Aspirates from the hypopharyngeal region of asymptomatic 1-mo-old infants were cultured for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Wheeze was monitored prospectively on diary cards during the first 5 years of life. Blood eosinophil count and total IgE and specific IgE were measured at 4 years of age. Lung function was measured and asthma was diagnosed at 5 years of age. RESULTS Hypopharyngeal samples were cultured from 321 neonates at 1 mo of age. Twenty-one percent of the infants were colonized with S. pneumoniae, M. catarrhalis, H. influenzae, or a combination of these organisms; colonization with one or more of these organisms, but not colonization with S. aureus, was significantly assocd. with persistent wheeze (hazard ratio, 2.40; 95% confidence interval [CI], 1.45 to 3.99), acute severe exacerbation of wheeze (hazard ratio, 2.99; 95% CI, 1.66 to 5.39), and hospitalization for wheeze (hazard ratio, 3.85; 95% CI, 1.90 to 7.79). Blood eosinophil counts and total IgE at 4 years of age were significantly increased in children colonized neonatally with S. pneumoniae, M. catarrhalis, H. influenzae, or a combination of these organisms, but specific IgE was not significantly affected. The prevalence of asthma and the reversibility of airway resistance after β2-agonist administration at 5 years of age were significantly increased in the children colonized neonatally with these organisms as compared with the children without such colonization (33% vs. 10% and 23% vs. 18%, resp.). CONCLUSIONS Neonates colonized in the hypopharyngeal region with S. pneumoniae, H. influenzae, or M. catarrhalis, or with a combination of these organisms, are at increased risk for recurrent wheeze and asthma early in life.
- 96Kraft, M. The Role of Bacterial Infections in Asthma. Clin. Chest. Med. 2000, 21, 301– 313, DOI: 10.1016/S0272-5231(05)70268-9Google Scholar96https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD3M%252Fis1Ohsw%253D%253D&md5=57256c2a28a4b7fc99df142c897d3711The role of bacterial infections in asthmaKraft MClinics in chest medicine (2000), 21 (2), 301-13 ISSN:0272-5231.In summary, bacterial organisms are clinically relevant contributors to asthma exacerbations, and have received much less attention than viruses in this process. Streptococcus pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis have been linked to asthma exacerbations, particularly when sinusitis is present. Treatment therefore should be directed toward these organisms if a bacterial cause is suspected. The atypical bacteria--specifically, C. pneumoniae and M. pneumoniae--deserve special attention. Data suggest a link between these organisms and the exacerbation of asthma, as well as suggest that these organisms may be causative in asthma development. The existing data are not conclusive, but are suggestive enough to drive studies evaluating them as a possible mechanism in asthma pathogenesis. An animal model evaluating M. pneumoniae and C. pneumoniae would be ideal, but at present no model exists in which chronic infection with these organisms results in bronchial hyperresponsiveness. There is active work in this area, however. Alternative investigations include continued evaluation of these organisms by several modalities, including culture, serology, and PCR, along with evaluation of the host response. Many questions remain, but the ground is fertile for continued investigation.
- 97Sethi, S.; Evans, N.; Grant, B. J.; Murphy, T. F. New Strains of Bacteria and Exacerbations of Chronic Obstructive Pulmonary Disease. N. Engl. J. Med. 2002, 347, 465– 471, DOI: 10.1056/NEJMoa012561Google Scholar97https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD38visVOksQ%253D%253D&md5=952109d5bc10776ba32ed5080eff1f42New strains of bacteria and exacerbations of chronic obstructive pulmonary diseaseSethi Sanjay; Evans Nancy; Grant Brydon J B; Murphy Timothy FThe New England journal of medicine (2002), 347 (7), 465-71 ISSN:.BACKGROUND: The role of bacterial pathogens in acute exacerbations of chronic obstructive pulmonary disease is controversial. In older studies, the rates of isolation of bacterial pathogens from sputum were the same during acute exacerbations and during stable disease. However, these studies did not differentiate among strains within a bacterial species and therefore could not detect changes in strains over time. We hypothesized that the acquisition of a new strain of a pathogenic bacterial species is associated with exacerbation of chronic obstructive pulmonary disease. METHODS: We conducted a prospective study in which clinical information and sputum samples for culture were collected monthly and during exacerbations from 81 outpatients with chronic obstructive pulmonary disease. Molecular typing of sputum isolates of nonencapsulated Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa was performed. RESULTS: Over a period of 56 months, the 81 patients made a total of 1975 clinic visits, 374 of which were made during exacerbations (mean, 2.1 per patient per year). On the basis of molecular typing, an exacerbation was diagnosed at 33.0 percent of the clinic visits that involved isolation of a new strain of a bacterial pathogen, as compared with 15.4 percent of visits at which no new strain was isolated (P<0.001; relative risk of an exacerbation, 2.15; 95 percent confidence interval, 1.83 to 2.53). Isolation of a new strain of H. influenzae, M. catarrhalis, or S. pneumoniae was associated with a significantly increased risk of an exacerbation. CONCLUSIONS: The association between an exacerbation and the isolation of a new strain of a bacterial pathogen supports the causative role of bacteria in exacerbations of chronic obstructive pulmonary disease.
- 98Dickson, R. P.; Erb-Downward, J. R.; Martinez, F. J.; Huffnagle, G. B. The Microbiome and the Respiratory Tract. Annu. Rev. Physiol. 2016, 78, 481– 504, DOI: 10.1146/annurev-physiol-021115-105238Google Scholar98https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhslGlsr7J&md5=ee2395d885e29bb5c02eebd019df54eaThe Microbiome and the Respiratory TractDickson, Robert P.; Erb-Downward, John R.; Martinez, Fernando J.; Huffnagle, Gary B.Annual Review of Physiology (2016), 78 (), 481-504CODEN: ARPHAD; ISSN:0066-4278. (Annual Reviews)A Review. Although the notion that "the normal lung is free from bacteria" remains common in textbooks, it is virtually always stated without citation or argument. The lungs are constantly exposed to diverse communities of microbes from the oropharynx and other sources, and over the past decade, novel culture-independent techniques of microbial identification have revealed that the lungs, previously considered sterile in health, harbor diverse communities of microbes. In this review, we describe the topog. and population dynamics of the respiratory tract, both in health and as altered by acute and chronic lung disease. We provide a survey of current techniques of sampling, sequencing, and anal. of respiratory microbiota and review tech. challenges and controversies in the field. We review and synthesize what is known about lung microbiota in various diseases and identify key lessons learned across disease states.
- 99Bassis, C. M.; Erb-Downward, J. R.; Dickson, R. P.; Freeman, C. M.; Schmidt, T. M.; Young, V. B.; Beck, J. M.; Curtis, J. L.; Huffnagle, G. B. Analysis of the Upper Respiratory Tract Microbiotas as the Source of the Lung and Gastric Microbiotas in Healthy Individuals. mBio 2015, 6, e00037-15 DOI: 10.1128/mBio.00037-15Google ScholarThere is no corresponding record for this reference.
- 100Hanada, S.; Pirzadeh, M.; Carver, K. Y.; Deng, J. C. Respiratory Viral Infection-Induced Microbiome Alterations and Secondary Bacterial Pneumonia. Front. Immunol. 2018, 9, 2640, DOI: 10.3389/fimmu.2018.02640Google Scholar100https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXosFelsLo%253D&md5=3f562cdc564799942eb1ca08f16ec590Respiratory viral infection-induced microbiome alterations and secondary bacterial pneumoniaHanada, Shigeo; Pirzadeh, Mina; Carver, Kyle Y.; Deng, Jane C.Frontiers in Immunology (2018), 9 (), 2640/1-2640/15CODEN: FIRMCW; ISSN:1664-3224. (Frontiers Media S.A.)A review. Influenza and other respiratory viral infections are the most common type of acute respiratory infection. Viral infections predispose patients to secondary bacterial infections, which often have a more severe clin. course. The mechanisms underlying post-viral bacterial infections are complex, and include multifactorial processes mediated by interactions between viruses, bacteria, and the host immune system. Studies over the past 15 years have demonstrated that unique microbial communities reside on the mucosal surfaces of the gastrointestinal tract and the respiratory tract, which have both direct and indirect effects on host defense against viral infections. In addn., antiviral immune responses induced by acute respiratory infections such as influenza are assocd. with changes in microbial compn. and function ("dysbiosis") in the respiratory and gastrointestinal tract, which in turn may alter subsequent immune function against secondary bacterial infection or alter the dynamics of inter-microbial interactions, thereby enhancing the proliferation of potentially pathogenic bacterial species. In this review, we summarize the literature on the interactions between host microbial communities and host defense, and how influenza, and other acute respiratory viral infections disrupt these interactions, thereby contributing to the pathogenesis of secondary bacterial infections.
- 101Soret, P.; Vandenborght, L. E.; Francis, F.; Coron, N.; Enaud, R.; Avalos, M.; Schaeverbeke, T.; Berger, P.; Fayon, M.; Thiebaut, R. Respiratory Mycobiome and Suggestion of Inter-Kingdom Network During Acute Pulmonary Exacerbation in Cystic Fibrosis. Sci. Rep. 2020, 10, 3589, DOI: 10.1038/s41598-020-60015-4Google Scholar101https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXlvVKiu7s%253D&md5=18e82e465ceb59d56b8101f756011f1aRespiratory mycobiome and suggestion of inter-kingdom network during acute pulmonary exacerbation in cystic fibrosisSoret, Perrine; Vandenborght, Louise-Eva; Francis, Florence; Coron, Noemie; Enaud, Raphael; Avalos, Marta; Schaeverbeke, Thierry; Berger, Patrick; Fayon, Michael; Thiebaut, Rodolphe; Delhaes, LaurenceScientific Reports (2020), 10 (1), 3589CODEN: SRCEC3; ISSN:2045-2322. (Nature Research)Abstr.: Lung infections play a crit. role in cystic fibrosis (CF) pathogenesis. CF respiratory tract is now considered to be a polymicrobial niche and advances in high-throughput sequencing allowed to analyze its microbiota and mycobiota. However, no NGS studies until now have characterized both communities during CF pulmonary exacerbation (CFPE). Thirty-three sputa isolated from patients with and without CFPE were used for metagenomic high-throughput sequencing targeting 16S and ITS2 regions of bacterial and fungal rRNA. We built inter-kingdom network and adapted Phy-Lasso method to highlight correlations in compositional data. The decline in respiratory function was assocd. with a decrease in bacterial diversity. The inter-kingdom network revealed three main clusters organized around Aspergillus, Candida, and Scedosporium genera. Using Phy-Lasso method, we identified Aspergillus and Malassezia as relevantly assocd. with CFPE, and Scedosporium plus Pseudomonas with a decline in lung function. We corroborated in vitro the cross-domain interactions between Aspergillus and Streptococcus predicted by the correlation network. For the first time, we included documented mycobiome data into a version of the ecol. Climax/Attack model that opens new lines of thoughts about the physiopathol. of CF lung disease and future perspectives to improve its therapeutic management.
- 102Worlitzsch, D.; Tarran, R.; Ulrich, M.; Schwab, U.; Cekici, A.; Meyer, K. C.; Birrer, P.; Bellon, G.; Berger, J.; Weiss, T. Effects of Reduced Mucus Oxygen Concentration in Airway Pseudomonas Infections of Cystic Fibrosis Patients. J. Clin. Invest. 2002, 109, 317– 325, DOI: 10.1172/JCI0213870Google Scholar102https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XhtV2isLo%253D&md5=de0c7ae4c8dcd98ccc450076f074e40fEffects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patientsWorlitzsch, Dieter; Tarran, Robert; Ulrich, Martina; Schwab, Ute; Cekici, Aynur; Meyer, Keith C.; Birrer, Peter; Bellon, Gabriel; Berger, Jurgen; Weiss, Tilo; Botzenhart, Konrad; Yankaskas, James R.; Randell, Scott; Boucher, Richard C.; Doring, GerdJournal of Clinical Investigation (2002), 109 (3), 317-325CODEN: JCINAO; ISSN:0021-9738. (American Society for Clinical Investigation)Current theories of CF pathogenesis predict different predisposing "local environmental" conditions and sites of bacterial infection within CF airways. Here we show that, in CF patients with established lung disease, Pseudomonas aeruginosa was located within hypoxic mucopurulent masses in airway lumens. In vitro studies revealed that CF-specific increases in epithelial O2 consumption, linked to increased airway surface liq. (ASL) vol. absorption and mucus stasis, generated steep hypoxic gradients within thickened mucus on CF epithelial surfaces prior to infection. Motile P. aeruginosa deposited on CF airway surfaces penetrated into hypoxic mucus zones and responded to this environment with increased alginate prodn. With P. aeruginosa growth in oxygen restricted environments, local hypoxia was exacerbated and frank anaerobiosis, as detected in vivo, resulted. These studies indicate that novel therapies for CF include removal of hypoxic mucus plaques and antibiotics effective against P. aeruginosa adapted to anaerobic environments.
- 103Schmidt, A.; Belaaouaj, A.; Bissinger, R.; Koller, G.; Malleret, L.; D’Orazio, C.; Facchinelli, M.; Schulte-Hubbert, B.; Molinaro, A.; Holst, O. Neutrophil Elastase-Mediated Increase in Airway Temperature During Inflammation. J. Cyst. Fibros. 2014, 13, 623– 631, DOI: 10.1016/j.jcf.2014.03.004Google Scholar103https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2cnhslyhsA%253D%253D&md5=21245c89975779531238f3fb8f4335d4Neutrophil elastase-mediated increase in airway temperature during inflammationSchmidt Annika; Bissinger Rosi; Doring Gerd; Belaaouaj Azzaq; Malleret Laurette; Koller Garrit; Bruce Kenneth; D'Orazio Ciro; Assael Baroukh; Facchinelli Martino; Piacentini Giorgio; Schulte-Hubbert Bernhard; Molinaro Antonio; Holst Otto; Haussler Susanne; Hammermann Jutta; Schniederjans Monika; Meyer Keith C; Damkiaer Soeren; LiPuma John J; Seelig Joachim; Worlitzsch DieterJournal of cystic fibrosis : official journal of the European Cystic Fibrosis Society (2014), 13 (6), 623-31 ISSN:.BACKGROUND: How elevated temperature is generated during airway infections represents a hitherto unresolved physiological question. We hypothesized that innate immune defence mechanisms would increase luminal airway temperature during pulmonary infection. METHODS: We determined the temperature in the exhaled air of cystic fibrosis (CF) patients. To further test our hypothesis, a pouch inflammatory model using neutrophil elastase-deficient mice was employed. Next, the impact of temperature changes on the dominant CF pathogen Pseudomonas aeruginosa growth was tested by plating method and RNAseq. RESULTS: Here we show a temperature of ~38°C in neutrophil-dominated mucus plugs of chronically infected CF patients and implicate neutrophil elastase:α1-proteinase inhibitor complex formation as a relevant mechanism for the local temperature rise. Gene expression of the main pathogen in CF, P. aeruginosa, under anaerobic conditions at 38°C vs 30°C revealed increased virulence traits and characteristic cell wall changes. CONCLUSION: Neutrophil elastase mediates increase in airway temperature, which may contribute to P. aeruginosa selection during the course of chronic infection in CF.
- 104Casadevall, A.; Pirofski, L. A. The Damage-Response Framework of Microbial Pathogenesis. Nat. Rev. Microbiol. 2003, 1, 17– 24, DOI: 10.1038/nrmicro732Google Scholar104https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXptFWlu74%253D&md5=9863a034a0ad7efa2c53e00ca5a10d44The damage-response framework of microbial pathogenesisCasadevall, Arturo; Pirofski, Liise-anneNature Reviews Microbiology (2003), 1 (1), 17-24CODEN: NRMACK; ISSN:1740-1526. (Nature Publishing Group)A review and discussion. The late twentieth century witnessed the emergence of numerous infectious diseases that are caused by microorganisms that rarely cause disease in normal, healthy immunocompetent hosts. The emergence of these diseases shows that the existing concepts of pathogenicity and virulence do not take into account the fact that both the microorganism and the host contribute to microbial pathogenesis. To address this impediment to studies of host-microorganism interactions,the authors propose a new theor. approach to understanding microbial pathogenesis, known as the "damage-response" framework.
- 105Freestone, P. P.; Hirst, R. A.; Sandrini, S. M.; Sharaff, F.; Fry, H.; Hyman, S.; O’Callaghan, C. Pseudomonas Aeruginosa-Catecholamine Inotrope Interactions: A Contributory Factor in the Development of Ventilator-Associated Pneumonia?. Chest 2012, 142, 1200– 1210, DOI: 10.1378/chest.11-2614Google Scholar105https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC38ngt1GgtA%253D%253D&md5=ff280d14b3619211c12a244175251d1dPseudomonas aeruginosa-catecholamine inotrope interactions: a contributory factor in the development of ventilator-associated pneumonia?Freestone Primrose P; Sandrini Sara M; Sharaff Fathima; Fry Helen; Hirst Robert A; Hyman Stefan; O'Callaghan ChrisChest (2012), 142 (5), 1200-1210 ISSN:.BACKGROUND: Ventilated patients receiving intensive care are at significant risk of acquiring a ventilator-associated pneumonia that is associated with significant morbidity and mortality. Despite intensive research, it is still unclear why Pseudomonas aeruginosa, a microbe that rarely causes pneumonia outside of intensive care, is responsible for so many of these infections. METHODS: We investigated whether medications frequently prescribed to patients in the ICU, the catecholamine inotropes, were affecting the growth and virulence of P aeruginosa . Effects of clinically attainable concentrations of inotropes on P aeruginosa pathogenicity were explored using in vitro growth and virulence assays and an ex vivo model of infection using ciliated human respiratory epithelium. RESULTS: We found that inotropes were potent stimulators of P aeruginosa growth, producing upto 50-fold increases in bacterial numbers via a mechanism involving inotrope delivery of transferrin-ron,internalization of the inotrope, and upregulation of the key pseudomonal siderophore pyoverdine.Inotropes also markedly increased biofilm formation on endotracheal tubing and enhanced the biofilm production and toxicity of P aeruginosa in its interaction with respiratory epithelium.Importantly, catecholamine inotropes also facilitated the rapid recovery of P aeruginosa from tobramycin antibiotic challenge. We also tested out the effect of the inotropes vasopressin and phenylephrine on the growth and virulence of P aeruginosa and found that, in contrast to the catecholamines,these drugs had no stimulatory effect. CONCLUSIONS: Collectively, our results suggest that catecholamine inotrope-bacterial interactions may be an unexpected contributory factor to the development of P aeruginosa -ventilator-associated pneumonia.
- 106Kanangat, S.; Meduri, G. U.; Tolley, E. A.; Patterson, D. R.; Meduri, C. U.; Pak, C.; Griffin, J. P.; Bronze, M. S.; Schaberg, D. R. Effects of Cytokines and Endotoxin on the Intracellular Growth of Bacteria. Infect. Immun. 1999, 67, 2834– 2840, DOI: 10.1128/IAI.67.6.2834-2840.1999Google Scholar106https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1MXjsFSgu74%253D&md5=a057d5d6948c52ff741b6cb9f2bd662fEffects of cytokines and endotoxin on the intracellular growth of bacteriaKanangat, Siva; Meduri, G. Umberto; Tolley, Elizabeth A.; Patterson, David R.; Meduri, Christopher U.; Pak, Chol; Griffin, John P.; Bronze, Michael S.; Schaberg, Dennis R.Infection and Immunity (1999), 67 (6), 2834-2840CODEN: INFIBR; ISSN:0019-9567. (American Society for Microbiology)Patients with unresolving acute respiratory distress syndrome (ARDS) have persistently elevated levels of proinflammatory cytokines in the lungs and circulation and increased rates of bacterial infections. Phagocytic cells hyperactivated with lipopolysaccharide (LPS), which induces high levels of proinflammatory cytokines in monocytes, are inefficient in killing ingested bacteria despite having intact phagocytic activity. Phagocytic cells that are activated with an analog of LPS that does not induce the expression of proinflammatory cytokines effectively ingest and kill bacteria. The authors hypothesized that in the presence of high concns. of proinflammatory cytokines, bacteria may adapt and utilize cytokines to their growth advantage. To test this hypothesis, the authors primed a human monocytic cell line (U937) with escalating concns. of the proinflammatory cytokines tumor necrosis factor α, interleukin-1β (IL-1β), and IL-6 and with LPS. These cells were then exposed to fresh isolates of 3 common nosocomial pathogens: Staphylococcus aureus, Pseudomonas aeruginosa, and an Acinetobacter sp. In human monocytes primed with lower concns. of proinflammatory cytokines (10-250 pg) or LPS (1 and 10 ng), intracellular bacterial growth decreased. However, when human monocytes were primed with higher concns. of proinflammatory cytokines (1-10 ng) or LPS (1-10 μg), intracellular growth of the tested bacteria increased. These results were reproduced with peripheral blood monocytes obtained from normal healthy volunteers. The specificity of the cytokine activity was demonstrated by neutralizing the cytokines with specific antibodies. These findings provide a possible mechanism to explain the frequent development of bacterial infections in patients with an intense and protracted inflammatory response.
- 107Kaza, S. K.; McClean, S.; Callaghan, M. Il-8 Released from Human Lung Epithelial Cells Induced by Cystic Fibrosis Pathogens Burkholderia Cepacia Complex Affects the Growth and Intracellular Survival of Bacteria. Int. J. Med. Microbiol. 2011, 301, 26– 33, DOI: 10.1016/j.ijmm.2010.06.005Google Scholar107https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsV2jtL%252FE&md5=a8488ab7fa4f9a5648b0a1f4f96942e2IL-8 released from human lung epithelial cells induced by cystic fibrosis pathogens Burkholderia cepacia complex affects the growth and intracellular survival of bacteriaKaza, Seshu K.; McClean, Siobhan; Callaghan, MaireInternational Journal of Medical Microbiology (2011), 301 (1), 26-33CODEN: IMEMFV; ISSN:1438-4221. (Elsevier GmbH)Burkholderia cepacia complex (Bcc) is a group of Gram-neg. pulmonary pathogens assocd. with life-threatening infections in patients with cystic fibrosis (CF). The airway epithelium plays a crucial role in the initiation and modulation of inflammatory responses to these pathogens. Interleukin (IL)-8 released from epithelial cells is a potent chemoattractant for neutrophils. The aims of this study were to compare the IL-8 response to Bcc infection in different epithelial cell types and to investigate the impact of IL-8 on Bcc growth and intracellular survival. To compare epithelial cell IL-8 responses, 4 human epithelial cell lines were used in the study; A549 cells, an alveolar epithelial cell line, Calu-3 cells, a sub-bronchial epithelial cell line, 16HBE14o- cells, and CFBE41o- cells, which are CFTR-pos. and CFTR-neg. bronchial epithelial cell lines, resp. Two B. multivorans and 2 B. cenocepacia strains all induced a significant IL-8 response by 12 h and further increased in all cell lines at 24 h. Furthermore, the levels of IL-8 from Calu-3 and A549 cells were approx. 3 times that of 16HBE14o- or CFBE41o- cells. In 2 of the cell lines examd. (16HBE14o- and CFBE41o-), B. cenocepacia LMG 16656 (J2315), an epidemic strain, induced greater levels of IL-8 (P < 0.01) compared to other Bcc strains tested. The CFTR-pos. and -neg. cell lines secreted similar levels of IL-8 indicating a CFTR-independent induction of IL-8. However, the CFTR-neg. cells did secrete constitutive levels of IL-8 greater than that of CFTR-pos. cells. An investigation of the effect of IL-8 on Bcc extracellular and intracellular growth found that at low concns. (<10 ng/mL) of recombinant human (rh) IL-8, the growth of B. cenocepacia LMG 16656 and B. multivorans LMG 13010 was enhanced, whereas at higher concns. (10 ng/mL), growth of both strains was significantly reduced. Growth of both non-CF Bcc strains remained unchanged in the presence of rhIL-8. In contrast to extracellular growth, higher concns. (10 ng/mL) of rhIL-8 enhance the intracellular growth and survival of both LMG 16656 and LMG 13010 in 16HBE14o- and CFBE41o- cell lines. Although LMG 13010 uptake by epithelial cells was higher than LMG 16656 (P < 0.01), the intracellular growth of LMG 16656 is greater than LMG 13010 (P < 0.05). These studies demonstrated that the type of epithelial cells encountered by Bcc strains dets. the extent of the IL-8 responses triggered and that this cytokine in addn. to its well-established proinflammatory properties can enhance both the extracellular and intracellular growth of Bcc strains.
- 108Lyte, M.; Ernst, S. Catecholamine Induced Growth of Gram Negative Bacteria. Life Sci. 1992, 50, 203– 212, DOI: 10.1016/0024-3205(92)90273-RGoogle Scholar108https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK38XjslOltQ%253D%253D&md5=8e7928b8179786f9588e74b4ff003472Catecholamine induced growth of gram negative bacteriaLyte, Mark; Ernst, SharonLife Sciences (1992), 50 (3), 203-12CODEN: LIFSAK; ISSN:0024-3205.The addn. of various catecholamines to cultures of gram-neg. bacteria resulted in dramatic increases in growth. The ability of norepinephrine, epinephrine, dopamine, and dopa to enhance the growth of Escherichia coli, Yersinia enterocolitica, and Pseudomonas aeruginosa was dependent on the bacterium employed, with each strain showing marked preference for 1 or more of the catecholamines. Catecholamine-induced increases in growth were confirmed by ≥1 of the following methods: uptake of tritiated thymidine into newly synthesized DNA, changes in optical d., or pour plate anal. None of the catecholamine metabolites resulting from either oxidative deamination or catechol O-methylation effected increases in bacterial growth similar to norepinephrine, epinephrine, or dopamine. Norepinephrine consistently caused the greatest increase in bacterial growth for all strains tested.
- 109Dickson, R. P.; Martinez, F. J.; Huffnagle, G. B. The Role of the Microbiome in Exacerbations of Chronic Lung Diseases. Lancet 2014, 384, 691– 702, DOI: 10.1016/S0140-6736(14)61136-3Google Scholar109https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsV2nurbO&md5=45eef30b5fa0dde1f9259ac166b66d4aThe role of the microbiome in exacerbations of chronic lung diseasesDickson, Robert P.; Martinez, Fernando J.; Huffnagle, Gary B.Lancet (2014), 384 (9944), 691-702CODEN: LANCAO; ISSN:0140-6736. (Elsevier Ltd.)A review. Culture-independent microbiol. techniques have shown a previously unappreciated complexity to the bacterial microbiome of the respiratory tract that forces reconsideration of the interactions between host, bacteria, and the pathogenesis of exacerbations of chronic lung disease. The compn. of the lung microbiome is detd. by microbial immigration, elimination, and relative growth rates of its members. All these factors change dramatically in chronic lung disease and further during exacerbations. Exacerbations lack the features of bacterial infections, including increased bacterial burden and decreased diversity of microbial communities. We propose that exacerbations are occasions of respiratory tract dysbiosis-a disorder of the respiratory tract microbial ecosystem with neg. effects on host biol. Respiratory tract dysbiosis provokes a dysregulated host immune response, which in turn alters growth conditions for microbes in airways, promoting further dysbiosis and perpetuating a cycle of inflammation and disordered microbiota. Differences in the compn. of baseline respiratory tract microbiota might help to explain the so-called frequent-exacerbator phenotype obsd. in several disease states, and might provide novel targets for therapeutic intervention.
- 110Byrd, A. L.; Belkaid, Y.; Segre, J. A. The Human Skin Microbiome. Nat. Rev. Microbiol. 2018, 16, 143– 155, DOI: 10.1038/nrmicro.2017.157Google Scholar110https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXovVCjtw%253D%253D&md5=7e3d5226179541f1f89222482b390950The human skin microbiomeByrd, Allyson L.; Belkaid, Yasmine; Segre, Julia A.Nature Reviews Microbiology (2018), 16 (3), 143-155CODEN: NRMACK; ISSN:1740-1526. (Nature Research)A review. Functioning as the exterior interface of the human body with the environment, skin acts as a phys. barrier to prevent the invasion of foreign pathogens while providing a home to the commensal microbiota. The harsh phys. landscape of skin, particularly the desiccated, nutrient-poor, acidic environment, also contributes to the adversity that pathogens face when colonizing human skin. Despite this, the skin is colonized by a diverse microbiota. In this Review, we describe amplicon and shotgun metagenomic DNA sequencing studies that have been used to assess the taxonomic diversity of microorganisms that are assocd. with skin from the kingdom to the strain level. We discuss recent insights into skin microbial communities, including their compn. in health and disease, the dynamics between species and interactions with the immune system, with a focus on Propionibacterium acnes, Staphylococcus epidermidis and Staphylococcus aureus.
- 111Adamczyk, K.; Garncarczyk, A.; Antonczak, P.; Wcislo-Dziadecka, D. The Foot Microbiome. J. Cosmet. Dermatol. 2020, 19, 1039– 1043, DOI: 10.1111/jocd.13368Google Scholar111https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB383isVyjsA%253D%253D&md5=2e510c009ab75dbf54139a6cace85ce5The foot microbiomeAdamczyk Katarzyna; Garncarczyk Agnieszka; Antonczak Pawel; Wcislo-Dziadecka DominikaJournal of cosmetic dermatology (2020), 19 (5), 1039-1043 ISSN:.BACKGROUND: The human skin microbiome is represented by bacteria, fungi, viruses, and mites. AIMS: Every human being possess their own unique skin microbiome because intrinsic and environmental factors have a significant impact on the quality and quantity of microorganism. Every site of the body is a separate microbial niche. PATIENTS: The feet are one of the most unique and heterogeneous microbial niches of human body with areas that differ by skin thickness, anatomical features, distribution of sweat glands, pH, and the availability of oxygen. RESULTS: Healthy skin of the foot is inhabited by Corynebacteriaceae, Micrococcaceae, Propionibacteriaceae, Actinobacteria, Clostridiales, Lactobacillaceae, Streptococcaceae, Enterobacteriaceae, Moravellaceae, Neisseriaceae, Pastereullaceae, and Proteobacteria. The most common fungi present on the feet are Malassezzia, Cryptococcus, Aspergillus, Rhodotorula, Epicoccum, Saccharomyces, Candida, Epidermophyton Microsporum, and Trichophyton. CONCLUSIONS: The disturbance of the foot microbiome causes dysbiosis and may lead to pitted keratolysis, fungal, and viral infections or even to protothecosis.
- 112Costello, E. K.; Lauber, C. L.; Hamady, M.; Fierer, N.; Gordon, J. I.; Knight, R. Bacterial Community Variation in Human Body Habitats across Space and Time. Science 2009, 326, 1694– 1697, DOI: 10.1126/science.1177486Google Scholar112https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhsFGmsL7K&md5=bc016e97bdcd143c0d46e2b8d496953bBacterial Community Variation in Human Body Habitats Across Space and TimeCostello, Elizabeth K.; Lauber, Christian L.; Hamady, Micah; Fierer, Noah; Gordon, Jeffrey I.; Knight, RobScience (Washington, DC, United States) (2009), 326 (5960), 1694-1697CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)Elucidating the biogeog. of bacterial communities on the human body is crit. for establishing healthy baselines from which to detect differences assocd. with diseases. To obtain an integrated view of the spatial and temporal distribution of the human microbiota, we surveyed bacteria from up to 27 sites in seven to nine healthy adults on four occasions. We found that community compn. was detd. primarily by body habitat. Within habitats, interpersonal variability was high, whereas individuals exhibited minimal temporal variability. Several skin locations harbored more diverse communities than the gut and mouth, and skin locations differed in their community assembly patterns. These results indicate that our microbiota, although personalized, varies systematically across body habitats and time; such trends may ultimately reveal how microbiome changes cause or prevent disease.
- 113Grice, E. A.; Kong, H. H.; Conlan, S.; Deming, C. B.; Davis, J.; Young, A. C.; NISC Comparative Sequencing Program; Bouffard, G. G.; Blakesley, R. W.; Murray, P. R. Topographical and Temporal Diversity of the Human Skin Microbiome. Science 2009, 324, 1190– 1192, DOI: 10.1126/science.1171700Google Scholar113https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXmsVGis7c%253D&md5=f8853d53fd19f4851a9a437fafdb341dTopographical and Temporal Diversity of the Human Skin MicrobiomeGrice, Elizabeth A.; Kong, Heidi H.; Conlan, Sean; Deming, Clayton B.; Davis, Joie; Young, Alice C.; Bouffard, Gerard G.; Blakesley, Robert W.; Murray, Patrick R.; Green, Eric D.; Turner, Maria L.; Segre, Julia A.Science (Washington, DC, United States) (2009), 324 (5931), 1190-1192CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)Human skin is a large, heterogeneous organ that protects the body from pathogens while sustaining microorganisms that influence human health and disease. Our anal. of 16S rRNA gene sequences obtained from 20 distinct skin sites of healthy humans revealed that physiol. comparable sites harbor similar bacterial communities. The complexity and stability of the microbial community are dependent on the specific characteristics of the skin site. This topog. and temporal survey provides a baseline for studies that examine the role of bacterial communities in disease states and the microbial interdependencies required to maintain healthy skin.
- 114Grice, E. A.; Segre, J. A. The Skin Microbiome. Nat. Rev. Microbiol. 2011, 9, 244– 253, DOI: 10.1038/nrmicro2537Google Scholar114https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXjt1Wnsrc%253D&md5=39e68804549f5150296ced8ae02afb5bThe skin microbiomeGrice, Elizabeth A.; Segre, Julia A.Nature Reviews Microbiology (2011), 9 (4), 244-253CODEN: NRMACK; ISSN:1740-1526. (Nature Publishing Group)A review. The skin is the human body's largest organ, colonized by a diverse milieu of microorganisms, most of which are harmless or even beneficial to their host. Colonization is driven by the ecol. of the skin surface, which is highly variable depending on topog. location, endogenous host factors and exogenous environmental factors. The cutaneous innate and adaptive immune responses can modulate the skin microbiota, but the microbiota also functions in educating the immune system. The development of mol. methods to identify microorganisms has led to an emerging view of the resident skin bacteria as highly diverse and variable. An enhanced understanding of the skin microbiome is necessary to gain insight into microbial involvement in human skin disorders and to enable novel promicrobial and antimicrobial therapeutic approaches for their treatment.
- 115Oh, J.; Byrd, A. L.; Deming, C.; Conlan, S.; NISC Comparative Sequencing Program; Kong, H. H.; Segre, J. A. Biogeography and Individuality Shape Function in the Human Skin Metagenome. Nature 2014, 514, 59– 64, DOI: 10.1038/nature13786Google Scholar115https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhs1yhsLjL&md5=d32d08e03fd0cd3eebd48578e0ca7bacBiogeography and individuality shape function in the human skin metagenomeOh, Julia; Byrd, Allyson L.; Deming, Clay; Conlan, Sean; Barnabas, Betty; Blakesley, Robert; Bouffard, Gerry; Brooks, Shelise; Coleman, Holly; Dekhtyar, Mila; Gregory, Michael; Guan, Xiaobin; Gupta, Jyoti; Han, Joel; Ho, Shi-ling; Legaspi, Richelle; Maduro, Quino; Masiello, Cathy; Maskeri, Baishali; McDowell, Jenny; Montemayor, Casandra; Mullikin, James; Park, Morgan; Riebow, Nancy; Schandler, Karen; Schmidt, Brian; Sison, Christina; Stantripop, Mal; Thomas, James; Thomas, Pamela; Vemulapalli, Meg; Young, Alice; Kong, Heidi H.; Segre, Julia A.Nature (London, United Kingdom) (2014), 514 (7520), 59-64CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)The varied topog. of human skin offers a unique opportunity to study how the body's microenvironments influence the functional and taxonomic compn. of microbial communities. Phylogenetic marker gene-based studies have identified many bacteria and fungi that colonize distinct skin niches. Here metagenomic analyses of diverse body sites in healthy humans demonstrate that local biogeog. and strong individuality define the skin microbiome. We developed a relational anal. of bacterial, fungal and viral communities, which showed not only site specificity but also individual signatures. We further identified strain-level variation of dominant species as heterogeneous and multiphyletic. Ref.-free analyses captured the uncharacterized metagenome through the development of a multi-kingdom gene catalog, which was used to uncover genetic signatures of species lacking ref. genomes. This work is foundational for human disease studies investigating inter-kingdom interactions, metabolic changes and strain tracking, and defines the dual influence of biogeog. and individuality on microbial compn. and function.
- 116Findley, K.; Oh, J.; Yang, J.; Conlan, S.; Deming, C.; Meyer, J. A.; Schoenfeld, D.; Nomicos, E.; Park, M.; NIH Intramural Sequencing Center Comparative Sequencing Program Topographic Diversity of Fungal and Bacterial Communities in Human Skin. Nature 2013, 498, 367– 370, DOI: 10.1038/nature12171Google Scholar116https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXotFSgtrw%253D&md5=12526f079a8b0d3c3da94562b27a2b47Topographic diversity of fungal and bacterial communities in human skinFindley, Keisha; Oh, Julia; Yang, Joy; Conlan, Sean; Deming, Clayton; Meyer, Jennifer A.; Schoenfeld, Deborah; Nomicos, Effie; Park, Morgan; Becker, Jesse; Benjamin, Betty; Blakesley, Robert; Bouffard, Gerry; Brooks, Shelise; Coleman, Holly; Dekhtyar, Mila; Gregory, Michael; Guan, Xiaobin; Gupta, Jyoti; Han, Joel; Hargrove, April; Ho, Shi-ling; Johnson, Taccara; Legaspi, Richelle; Lovett, Sean; Maduro, Quino; Masiello, Cathy; Maskeri, Baishali; McDowell, Jenny; Montemayor, Casandra; Mullikin, James; Park, Morgan; Riebow, Nancy; Schandler, Karen; Schmidt, Brian; Sison, Christina; Stantripop, Mal; Thomas, James; Thomas, Pam; Vemulapalli, Meg; Young, Alice; Kong, Heidi H.; Segre, Julia A.Nature (London, United Kingdom) (2013), 498 (7454), 367-370CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)Traditional culture-based methods have incompletely defined the microbial landscape of common recalcitrant human fungal skin diseases, including athlete's foot and toenail infections. Skin protects humans from invasion by pathogenic microorganisms and provides a home for diverse commensal microbiota. Bacterial genomic sequence data have generated novel hypotheses about species and community structures underlying human disorders. However, microbial diversity is not limited to bacteria; microorganisms such as fungi also have major roles in microbial community stability, human health and disease. Genomic methodologies to identify fungal species and communities have been limited compared with those that are available for bacteria. Fungal evolution can be reconstructed with phylogenetic markers, including rRNA gene regions and other highly conserved genes. Here, the authors sequenced and analyzed fungal communities of 14 skin sites in 10 healthy adults. Eleven core-body and arm sites were dominated by fungi of the genus Malassezia, with only species-level classifications revealing fungal-community compn. differences between sites. By contrast, three foot sites-plantar heel, toenail and toe web-showed high fungal diversity. Concurrent anal. of bacterial and fungal communities demonstrated that physiol. attributes and topog. of skin differentially shape these two microbial communities. These results provide a framework for future investigation of the contribution of interactions between pathogenic and commensal fungal and bacterial communities to the maintenance of human health and to disease pathogenesis.
- 117Oh, J.; Byrd, A. L.; Park, M.; NISC Comparative Sequencing Program; Kong, H. H.; Segre, J. A. Temporal Stability of the Human Skin Microbiome. Cell 2016, 165, 854– 866, DOI: 10.1016/j.cell.2016.04.008Google Scholar117https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XnslKitrg%253D&md5=e0217b043feae8a91e40e462239560cfTemporal Stability of the Human Skin MicrobiomeOh, Julia; Byrd, Allyson L.; Park, Morgan; Kong, Heidi H.; Segre, Julia A.Cell (Cambridge, MA, United States) (2016), 165 (4), 854-866CODEN: CELLB5; ISSN:0092-8674. (Cell Press)Biogeog. and individuality shape the structural and functional compn. of the human skin microbiome. To explore these factors' contribution to skin microbial community stability, we generated metagenomic sequence data from longitudinal samples collected over months and years. Analyzing these samples using a multi-kingdom, ref.-based approach, we found that despite the skin's exposure to the external environment, its bacterial, fungal, and viral communities were largely stable over time. Site, individuality, and phylogeny were all determinants of stability. Foot sites exhibited the most variability; individuals differed in stability; and transience was a particular characteristic of eukaryotic viruses, which showed little site-specificity in colonization. Strain and single-nucleotide variant-level anal. showed that individuals maintain, rather than reacquire, prevalent microbes from the environment. Longitudinal stability of skin microbial communities generates hypotheses about colonization resistance and empowers clin. studies exploring alterations obsd. in disease states.
- 118Feng, H.; Shuda, M.; Chang, Y.; Moore, P. S. Clonal Integration of a Polyomavirus in Human Merkel Cell Carcinoma. Science 2008, 319, 1096– 1100, DOI: 10.1126/science.1152586Google Scholar118https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXit1yhsbY%253D&md5=79c4e37f638b771e22a19c78a41a0002Clonal Integration of a Polyomavirus in Human Merkel Cell CarcinomaFeng, Huichen; Shuda, Masahiro; Chang, Yuan; Moore, Patrick S.Science (Washington, DC, United States) (2008), 319 (5866), 1096-1100CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)Merkel cell carcinoma (MCC) is a rare but aggressive human skin cancer that typically affects elderly and immunosuppressed individuals, a feature suggestive of an infectious origin. The authors studied MCC samples by digital transcriptome subtraction and detected a fusion transcript between a previously undescribed virus T antigen and a human receptor tyrosine phosphatase. Further investigation led to identification and sequence anal. of the 5387-base-pair genome of a previously unknown polyomavirus that we call Merkel cell polyomavirus (MCV or MCPyV). MCV sequences were detected in 8 of 10 (80%) MCC tumors but only 5 of 59 (8%) control tissues from various body sites and 4 of 25 (16%) control skin tissues. In six of eight MCV-pos. MCCs, viral DNA was integrated within the tumor genome in a clonal pattern, suggesting that MCV infection and integration preceded clonal expansion of the tumor cells. Thus, MCV may be a contributing factor in the pathogenesis of MCC.
- 119Hannigan, G. D.; Meisel, J. S.; Tyldsley, A. S.; Zheng, Q.; Hodkinson, B. P.; SanMiguel, A. J.; Minot, S.; Bushman, F. D.; Grice, E. A. The Human Skin Double-Stranded DNA Virome: Topographical and Temporal Diversity, Genetic Enrichment, and Dynamic Associations with the Host Microbiome. mBio 2015, 6, e01578-15, DOI: 10.1128/mBio.01578-15Google ScholarThere is no corresponding record for this reference.
- 120Scharschmidt, T. C.; Fischbach, M. A. What Lives on Our Skin: Ecology, Genomics and Therapeutic Opportunities of the Skin Microbiome. Drug Discovery Today Dis. Mech. 2013, 10, e83– e89, DOI: 10.1016/j.ddmec.2012.12.003Google ScholarThere is no corresponding record for this reference.
- 121Holland, K. T.; Greenman, J.; Cunliffe, W. J. Growth of Cutaneous Propionibacteria on Synthetic Medium; Growth Yields and Exoenzyme Production. J. Appl. Bacteriol. 1979, 47, 383– 394, DOI: 10.1111/j.1365-2672.1979.tb01198.xGoogle Scholar121https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL3cXptVGmtw%253D%253D&md5=b83f218aa7c2902471f87753680b2fcfGrowth of cutaneous propionibacteria on synthetic medium; growth yields and exoenzyme productionHolland, K. T.; Greenman, J.; Cunliffe, W. J.Journal of Applied Bacteriology (1979), 47 (3), 383-94CODEN: JABAA4; ISSN:0021-8847.A synthetic medium contg. only low mol. wt. components was developed to grow Propionibacterium acnes, P. acidum, and P. granulosum. The medium supported the growth of 30/32 typed strains, and when solidified with agar supported the growth of these bacteria isolated directly from the skin. The mean overall efficiency of isolation on the synthetic medium was 57% that of reinforced clostridial medium (RCM). Batch culture expts. with glucose, fructose, glycerol, or arginine in the medium showed that the concns. as well as the type of C energy sources used could effect growth and exocellular enzyme (lipase, hyaluronidase, and acid phosphatase) prodn. by these organisms.
- 122Bruggemann, H.; Henne, A.; Hoster, F.; Liesegang, H.; Wiezer, A.; Strittmatter, A.; Hujer, S.; Durre, P.; Gottschalk, G. The Complete Genome Sequence of Propionibacterium Acnes, a Commensal of Human Skin. Science 2004, 305, 671– 673, DOI: 10.1126/science.1100330Google Scholar122https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2czotlemuw%253D%253D&md5=8229168995889d43312ae6edacd01d61The complete genome sequence of Propionibacterium acnes, a commensal of human skinBruggemann Holger; Henne Anke; Hoster Frank; Liesegang Heiko; Wiezer Arnim; Strittmatter Axel; Hujer Sandra; Durre Peter; Gottschalk GerhardScience (New York, N.Y.) (2004), 305 (5684), 671-3 ISSN:.Propionibacterium acnes is a major inhabitant of adult human skin, where it resides within sebaceous follicles, usually as a harmless commensal although it has been implicated in acne vulgaris formation. The entire genome sequence of this Gram-positive bacterium encodes 2333 putative genes and revealed numerous gene products involved in degrading host molecules, including sialidases, neuraminidases, endoglycoceramidases, lipases, and pore-forming factors. Surface-associated and other immunogenic factors have been identified, which might be involved in triggering acne inflammation and other P. acnes-associated diseases.
- 123Marples, R. R.; Downing, D. T.; Kligman, A. M. Control of Free Fatty Acids in Human Surface Lipids by Corynebacterium Acnes. J. Invest. Dermatol. 1971, 56, 127– 131, DOI: 10.1111/1523-1747.ep12260695Google Scholar123https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE3MXnsFSltQ%253D%253D&md5=35976db1cc211f1241eb1928f658e814Control of free fatty acids in human surface lipids by Corynebacterium acnesMarples, Richard R.; Downing, Donald T.; Kligman, Albert M.Journal of Investigative Dermatology (1971), 56 (2), 127-31CODEN: JIDEAE; ISSN:0022-202X.The linear relation between free fatty acids contents in human surface lipids and C. acnes population suggested that the organisms were the main source of the lipolytic enzymes, lipases. The d. of the aerobic cocci and yeasts in scalp flora were not affected by demethylchlortetracycline (600 mg/day, orally, 6 weeks) which selectively suppressed the d. of C. acnes.
- 124Ingham, E.; Holland, K. T.; Gowland, G.; Cunliffe, W. J. Partial Purification and Characterization of Lipase (Ec 3.1.1.3) from Propionibacterium Acnes. J. Gen. Microbiol. 1981, 124, 393– 401Google Scholar124https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL3MXlvF2mtL4%253D&md5=90a6e2c0eac3d6831c41e69a4a3aefbcPartial purification and characterization of lipase (EC 3.1.1.3) from Propionibacterium acnesIngham, Eileen; Holland, K. T.; Gowland, G.; Cunliffe, W. J.Journal of General Microbiology (1981), 124 (2), 393-401CODEN: JGMIAN; ISSN:0022-1287.Lipase (I) was purified 4800-fold from a crude culture supernatant of P. acnes and characterized. Purified I had no assayable proteinase, hyaluronate lyase, or acid phosphatase activities. The mol. wt. of I was 46,770 as detd. by gel filtration. SDS-polyacrylamide gel electrophoresis revealed a major protein component (mol. wt. = 41,190) together with 2 minor protein components (mol. wts. = 67,000 and 125,900). I had a pH optimum of 6.8, was most stable in the pH range 5.0-6.0, and was completely inactivated after 30 min at 60°. I hydrolyzed trilaurin, triolein, trimyristin, and tripalmitin at decreasing rates and did not exhibit phospholipase activity. Anal. of the reaction products from the hydrolysis of triolein by I did not demonstrate an accumulation of 2-monoolein, suggesting that I did not exhibit positional specificity for the 1-position of the triacylglycerol. Crude I prepns. contained an aggregated high-mol.-wt. form of the enzyme which was eluted with the void vol. for Sephadex G-200. This aggregated form was dissocd. to produce the lower-mol.-wt. I species by subsequent dialysis and elution from Sephadex G-200 using buffer with a higher ionic strength.
- 125Gribbon, E. M.; Cunliffe, W. J.; Holland, K. T. Interaction of Propionibacterium Acnes with Skin Lipids in Vitro. J. Gen. Microbiol. 1993, 139, 1745– 1751, DOI: 10.1099/00221287-139-8-1745Google Scholar125https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3sXms1Kgsb4%253D&md5=8fdd05d73069aed468269372156d2585Interaction of Propionibacterium acnes with skin lipids in vitroGribbon, E. M.; Cunliffe, W. J.; Holland, K. T.Journal of General Microbiology (1993), 139 (8), 1745-51CODEN: JGMIAN; ISSN:0022-1287.Propionibacterium acnes is the predominant microbial resident within the pilosebaceous follicles of sebum-rich areas of human skin. This study investigated the effects of known hydrophobic components of sebum on the physiol. and nutrition of this microorganism, grown anaerobically at 33 °C, under defined conditions using continuous culture techniques. The medium used was chem. defined, comprising eight amino acids, with glucose as the main carbon energy source, and the culture pH was maintained at 5.6. The range of sebum lipids assayed was based on the C18 monounsatd. fatty acid 9-cis-octadecenoic acid (oleic acid). Stock micronized solns. were aspetically pulsed into continuous cultures in the presence and absence of glucose, and nutritional effects were monitored. None of the lipid substrates significantly affected P. acnes growth either in terms of max. specific growth rate (μmax) or final culture biomass yield. Glycerol (3 mg mL-1) was found to be a poor carbon/energy source in comparison to glucose. Bacterial cells did, however, adhere with varying degrees to the different lipid species, with max. adherence occurring with the free fatty acid. This observation was confirmed by preliminary uptake expts. using [14C]oleic acid. The interactive site for cell adherence may be the lipid-fibrillar layer assocd. with the cell surface of P. acnes, as discerned in electron microscopical studies. The findings of this investigation suggest that one function of the P. acnes lipase may be to aid colonization within the pilosebaceous follicle, by promoting cell adherence to components such as oleic acid.
- 126Mukherjee, S.; Mitra, R.; Maitra, A.; Gupta, S.; Kumaran, S.; Chakrabortty, A.; Majumder, P. P. Sebum and Hydration Levels in Specific Regions of Human Face Significantly Predict the Nature and Diversity of Facial Skin Microbiome. Sci. Rep. 2016, 6, 36062, DOI: 10.1038/srep36062Google Scholar126https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhslKntrnJ&md5=5a70b8ef071be448b6b6336e863eb0c9Sebum and Hydration Levels in Specific Regions of Human Face Significantly Predict the Nature and Diversity of Facial Skin MicrobiomeMukherjee, Souvik; Mitra, Rupak; Maitra, Arindam; Gupta, Satyaranjan; Kumaran, Srikala; Chakrabortty, Amit; Majumder, Partha P.Scientific Reports (2016), 6 (), 36062CODEN: SRCEC3; ISSN:2045-2322. (Nature Publishing Group)The skin microbiome varies across individuals. The causes of these variations are inadequately understood. We tested the hypothesis that inter-individual variation in facial skin microbiome can be significantly explained by variation in sebum and hydration levels in specific facial regions of humans. We measured sebum and hydration from forehead and cheek regions of healthy female volunteers (n = 30). Metagenomic DNA from skin swabs were sequenced for V3-V5 regions of 16S rRNA gene. Altogether, 34 phyla were identified; predominantly Actinobacteria (66.3%), Firmicutes (17.7%), Proteobacteria (13.1%) and Bacteroidetes (1.4%). About 1000 genera were identified; predominantly Propionibacterium (58.6%), Staphylococcus (8.6%), Streptococcus (4.0%), Corynebacterium (3.6%) and Paracoccus (3.3%). A subset (n = 24) of individuals were sampled two months later. Stepwise multiple regression anal. showed that cheek sebum level was the most significant predictor of microbiome compn. and diversity followed by forehead hydration level; forehead sebum and cheek hydration levels were not. With increase in cheek sebum, the prevalence of Actinobacteria (p = 0.001)/Propionibacterium (p = 0.002) increased, whereas microbiome diversity decreased (Shannon Index, p = 0.032); this was opposite for other phyla/genera. These trends were reversed for forehead hydration levels. Therefore, the nature and diversity of facial skin microbiome is jointly detd. by site-specific lipid and water levels in the stratum corneum.
- 127Oh, J.; Conlan, S.; Polley, E. C.; Segre, J. A.; Kong, H. H. Shifts in Human Skin and Nares Microbiota of Healthy Children and Adults. Genome Med. 2012, 4, 77, DOI: 10.1186/gm378Google Scholar127https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3s%252FjvVCitA%253D%253D&md5=eceecdf6834d04cd846ee850da7bae53Shifts in human skin and nares microbiota of healthy children and adultsOh Julia; Conlan Sean; Segre Julia A; Polley Eric C; Kong Heidi HGenome medicine (2012), 4 (10), 77 ISSN:1756-994X.BACKGROUND: Characterization of the topographical and temporal diversity of the microbial collective (microbiome) hosted by healthy human skin established a reference for studying disease-causing microbiomes. Physiologic changes occur in the skin as humans mature from infancy to adulthood. Thus, characterizations of adult microbiomes might have limitations when considering pediatric disorders such as atopic dermatitis (AD) or issues such as sites of microbial carriage. The objective of this study was to determine if microbial communities at several body sites in children differed significantly from adults. METHODS: Using 16S-rRNA gene sequencing technology, we characterized and compared the bacterial communities of four body sites in relation to Tanner stage of human development. Body sites sampled included skin sites characteristically involved in AD (antecubital/popliteal fossae), a control skin site (volar forearm), and the nares. Twenty-eight healthy individuals aged from 2 to 40 years were evaluated at the outpatient dermatology clinic in the National Institutes of Health's Clinical Center. Exclusion criteria included the use of systemic antibiotics within 6 months, current/prior chronic skin disorders, asthma, allergic rhinitis, or other chronic medical conditions. RESULTS: Bacterial communities in the nares of children (Tanner developmental stage 1) differed strikingly from adults (Tanner developmental stage 5). Firmicutes (Streptococcaceae), Bacteroidetes, and Proteobacteria (β, γ) were overrepresented in Tanner 1 compared to Tanner 5 individuals, where Corynebacteriaceae and Propionibacteriaceae predominated. While bacterial communities were significantly different between the two groups in all sites, the most marked microbial shifts were observed in the nares, a site that can harbor pathogenic species, including Staphylococcus aureus and Streptococcus pneumonia. CONCLUSIONS: Significant shifts in the microbiota associated with progressive sexual maturation as measured by Tanner staging suggest that puberty-dependent shifts in the skin and nares microbiomes may have significant implications regarding prevention and treatment of pediatric disorders involving microbial pathogens and colonization.
- 128Jo, J. H.; Deming, C.; Kennedy, E. A.; Conlan, S.; Polley, E. C.; Ng, W. I.; NISC Comparative Sequencing Program; Segre, J. A.; Kong, H. H. Diverse Human Skin Fungal Communities in Children Converge in Adulthood. J. Invest. Dermatol. 2016, 136, 2356– 2363, DOI: 10.1016/j.jid.2016.05.130Google Scholar128https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsV2gsrzK&md5=161b0a052ce496b4f87b33dd23a6fb34Diverse Human Skin Fungal Communities in Children Converge in AdulthoodJo, Jay-Hyun; Deming, Clay; Kennedy, Elizabeth A.; Conlan, Sean; Polley, Eric C.; Ng, Weng-lan; Segre, Julia A.; Kong, Heidi H.Journal of Investigative Dermatology (2016), 136 (12), 2356-2363CODEN: JIDEAE; ISSN:0022-202X. (Elsevier Inc.)Understanding the skin mycobiome (fungal communities) is important because both commensal and pathogenic fungi can drive cutaneous disease depending on host status and body sites, including the scalp, feet, and groin. Interestingly, age may also affect skin fungal infections as certain dermatophytoses (i.e., tinea capitis) are more frequent in children than adults. We previously described the skin mycobiomes in healthy adults, showing lipophilic fungi Malassezia predominate in most skin sites. Because children have less sebaceous skin before puberty, we compared the fungal communities of primary clin. samples from healthy children and adults, based on sequencing of a fungal phylogenetic marker. Although Malassezia predominated on the trunk, head, and arm skin of adults (age 18-39), children (age < 14) had more diverse fungal communities, for example, Eurotiomycetes, which includes common dermatophytes. Species-level classification showed that Malassezia globosa predominated in children. Collectively, our findings indicate that prepubertal skin is colonized by diverse fungi, whereas adult skin is predominantly obligatory lipophilic Malassezia, suggesting that fungal communities on skin profoundly shift during puberty. Mycobiome shifts during puberty are likely due to alterations in sebaceous gland activation and sebum compn. This study provides a foundational framework for studies investigating interactions between fungi, skin, and pediatric dermatophytosis.
- 129Jo, J. H.; Kennedy, E. A.; Kong, H. H. Topographical and Physiological Differences of the Skin Mycobiome in Health and Disease. Virulence 2017, 8, 324– 333, DOI: 10.1080/21505594.2016.1249093Google Scholar129https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2srhvVahsQ%253D%253D&md5=7cd39569103bd48f48404bbb3658ed8fTopographical and physiological differences of the skin mycobiome in health and diseaseJo Jay-Hyun; Kennedy Elizabeth A; Kong Heidi HVirulence (2017), 8 (3), 324-333 ISSN:.Skin constantly encounters external elements, including microbes. Culture-based studies have identified fungi present on human skin and have linked some species with certain skin diseases. Moreover, modern medical treatments, especially immunosuppressants, have increased the population at risk for cutaneous and invasive fungal infections, emphasizing the need to understand skin fungal communities in health and disease. A major hurdle for studying fungal flora at a community level has been the heterogeneous culture conditions required by skin fungi. Recent advances in DNA sequencing technologies have dramatically expanded our knowledge of the skin microbiome through culture-free methods. This review discusses historical and recent research on skin fungal communities - the mycobiome - in health and disease, and challenges associated with sequencing-based mycobiome research.
- 130Kyriakis, K. P.; Terzoudi, S.; Palamaras, I.; Pagana, G.; Michailides, C.; Emmanuelides, S. Pityriasis Versicolor Prevalence by Age and Gender. Mycoses 2006, 49, 517– 518, DOI: 10.1111/j.1439-0507.2006.01285.xGoogle Scholar130https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD28nlt1ygsg%253D%253D&md5=c8616f44fad79eae60616a8758477226Pityriasis versicolor prevalence by age and genderKyriakis Kyriakos P; Terzoudi Sofia; Palamaras Ioulios; Pagana Georgia; Michailides Charalambos; Emmanuelides SmaroMycoses (2006), 49 (6), 517-8 ISSN:0933-7407.There is no expanded citation for this reference.
- 131Havlickova, B.; Czaika, V. A.; Friedrich, M. Epidemiological Trends in Skin Mycoses Worldwide. Mycoses 2008, 51, 2– 15, DOI: 10.1111/j.1439-0507.2008.01606.xGoogle Scholar131https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1cngtFyjtw%253D%253D&md5=112dc75472ee8b0d41bea06382f3d6c3Epidemiological trends in skin mycoses worldwideHavlickova Blanka; Czaika Viktor A; Friedrich MarkusMycoses (2008), 51 Suppl 4 (), 2-15 ISSN:.Fungal infections of the skin and nails are a common global problem. The high prevalence of superficial mycotic infections shows that 20-25% of the world's population has skin mycoses, making these one of the most frequent forms of infection. Pathogens responsible for skin mycoses are primarily anthropophilic and zoophilic dermatophytes from the genera Trichophyton (T.), Microsporum (M.) and Epidermophyton (E.). There appears to be considerable inter- and intra-continental variability in the global incidence of these fungal infections. Trichophyton rubrum, T. interdigitale (mentagrophytes var. interdigitale), M. canis, M. audouinii, T. tonsurans and T. verrucosum are the most common, but the attack rates and incidence of specific mycoses can vary widely. Local socio-economic conditions and cultural practices can also influence the prevalence of a particular infection in a given area. For example, tinea pedis (athlete's foot) is more prevalent in developed countries than in emerging economies and is likely to be caused by the anthropophilic germ T. rubrum. In poorer countries, scalp infections (tinea capitis) caused by T. soudanense or M. audouinii are more prevalent. This review summarises current epidemiological trends for fungal infections and focuses on dermatomycosis of glabrous skin on different continents.
- 132Seebacher, C.; Bouchara, J. P.; Mignon, B. Updates on the Epidemiology of Dermatophyte Infections. Mycopathologia 2008, 166, 335– 352, DOI: 10.1007/s11046-008-9100-9Google Scholar132https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1cnptVSnuw%253D%253D&md5=a873a26bcf50f5410773a33bf364ae1eUpdates on the epidemiology of dermatophyte infectionsSeebacher Claus; Bouchara Jean-Philippe; Mignon BernardMycopathologia (2008), 166 (5-6), 335-52 ISSN:0301-486X.The spectrum of dermatophytes isolated from skin lesions had changed in last 70 years. Before the Second World War in Germany, Microsporum audouinii and Epidermophyton floccosum ranked the first, whereas Trichophyton rubrum is the most common dermatophyte since the fifties of last century, accounting for 80-90% of the strains, followed by T. mentagrophytes. This evolution is typical for Central and North Europe and it needs to be connected with the increase in the incidence of tinea pedis. In contrast, in Southern Europe and in Arabic countries, zoophilic dermatophytes, such as Microsporum canis or Trichophyton verrucosum, are the most frequently isolated. In Europe, especially in Mediterranean countries, the incidence of M. canis infection has strongly increased during the recent years and this dermatophyte is now the most prevalent in tinea capitis in children. An analysis of the frequency and distribution of tinea pedis in different occupations and leisure-time activities as well as the routes of infection are reported. The spreading of this disease in most developed countries of the world represents a considerable economic problem, since it was accompanied by a parallel increase in the frequency of onychomycosis which implies, as tinea pedis, large financial charges. In poor developing countries, mycoses appear endemically, primarily with children, and their treatment often fails because of the lack of efficient antifungals. The particular epidemiological situations of dermatophytoses and the pathogenic spectrum of dermatophytes are examined at the example of numerous countries.
- 133Tomida, S.; Nguyen, L.; Chiu, B. H.; Liu, J.; Sodergren, E.; Weinstock, G. M.; Li, H. Pan-Genome and Comparative Genome Analyses of Propionibacterium Acnes Reveal Its Genomic Diversity in the Healthy and Diseased Human Skin Microbiome. mBio 2013, 4, e00003-13, DOI: 10.1128/mBio.00003-13Google ScholarThere is no corresponding record for this reference.
- 134Fitz-Gibbon, S.; Tomida, S.; Chiu, B. H.; Nguyen, L.; Du, C.; Liu, M.; Elashoff, D.; Erfe, M. C.; Loncaric, A.; Kim, J. Propionibacterium Acnes Strain Populations in the Human Skin Microbiome Associated with Acne. J. Invest. Dermatol. 2013, 133, 2152– 2160, DOI: 10.1038/jid.2013.21Google Scholar134https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXjtFSktrg%253D&md5=421ec3353e987d831694ff19b53e818bPropionibacterium acnes Strain Populations in the Human Skin Microbiome Associated with AcneFitz-Gibbon, Sorel; Tomida, Shuta; Chiu, Bor-Han; Nguyen, Lin; Du, Christine; Liu, Minghsun; Elashoff, David; Erfe, Marie C.; Loncaric, Anya; Kim, Jenny; Modlin, Robert L.; Miller, Jeff F.; Sodergren, Erica; Craft, Noah; Weinstock, George M.; Li, HuiyingJournal of Investigative Dermatology (2013), 133 (9), 2152-2160CODEN: JIDEAE; ISSN:0022-202X. (Nature Publishing Group)The human skin microbiome has important roles in skin health and disease. However, bacterial population structure and diversity at the strain level is poorly understood. We compared the skin microbiome at the strain level and genome level of Propionibacterium acnes, a dominant skin commensal, between 49 acne patients and 52 healthy individuals by sampling the pilosebaceous units on their noses. Metagenomic anal. demonstrated that although the relative abundances of P. acnes were similar, the strain population structures were significantly different in the two cohorts. Certain strains were highly assocd. with acne, and other strains were enriched in healthy skin. By sequencing 66 previously unreported P. acnes strains and comparing 71 P. acnes genomes, we identified potential genetic determinants of various P. acnes strains in assocn. with acne or health. Our anal. suggests that acquired DNA sequences and bacterial immune elements may have roles in detg. virulence properties of P. acnes strains, and some could be future targets for therapeutic interventions. This study demonstrates a previously unreported paradigm of commensal strain populations that could explain the pathogenesis of human diseases. It underscores the importance of strain-level anal. of the human microbiome to define the role of commensals in health and disease.
- 135Kang, D.; Shi, B.; Erfe, M. C.; Craft, N.; Li, H. Vitamin B12 Modulates the Transcriptome of the Skin Microbiota in Acne Pathogenesis. Sci. Transl. Med. 2015, 7, 293, DOI: 10.1126/scitranslmed.aab2009Google ScholarThere is no corresponding record for this reference.
- 136Picardo, M.; Ottaviani, M.; Camera, E.; Mastrofrancesco, A. Sebaceous Gland Lipids. Dermatoendocrinol. 2009, 1, 68– 71, DOI: 10.4161/derm.1.2.8472Google Scholar136https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3c7nvVSrsA%253D%253D&md5=338e05a80b7887b5197ad7fc3bf3855fSebaceous gland lipidsPicardo Mauro; Ottaviani Monica; Camera Emanuela; Mastrofrancesco AriannaDermato-endocrinology (2009), 1 (2), 68-71 ISSN:.The principal activity of mature sebaceous glands is producing and secreting sebum, which is a complex mixture of lipids. Sebum composition is different among species and this difference is probably due to the function that sebum has to absolve. In human sebum there are unique lipids, such as squalene and wax esters not found anywhere else in the body nor among the epidermal surface lipids. Moreover, they correspond to major components supplying the skin with protection. However, the ultimate role of human sebum, as well the metabolic pathways regulating its composition and secretion rate, are far from a complete understanding. Increased sebum secretion is considered, among all features, the major one involved in the pathophysiology of acne. Along with increased sebum secretion rate, quali- and quantitative modifications of sebum are likely to occur in this pathology. Understanding the factors and mechanisms that regulate sebum production is needed in order to identify new targets that can be addressed to achieve a selective modulation of lipid biosynthesis as a novel therapeutic strategy to correct lipid disregulations in acne and other disorders of the pilosebaceous unit.
- 137Jahns, A. C.; Lundskog, B.; Ganceviciene, R.; Palmer, R. H.; Golovleva, I.; Zouboulis, C. C.; McDowell, A.; Patrick, S.; Alexeyev, O. A. An Increased Incidence of Propionibacterium Acnes Biofilms in Acne Vulgaris: A Case-Control Study. Br. J. Dermatol. 2012, 167, 50– 58, DOI: 10.1111/j.1365-2133.2012.10897.xGoogle Scholar137https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC38vjvVOisQ%253D%253D&md5=63d0a0150848139144b2eaa412d19657An increased incidence of Propionibacterium acnes biofilms in acne vulgaris: a case-control studyJahns A C; Lundskog B; Ganceviciene R; Palmer R H; Golovleva I; Zouboulis C C; McDowell A; Patrick S; Alexeyev O AThe British journal of dermatology (2012), 167 (1), 50-8 ISSN:.BACKGROUND: Acne vulgaris is a disorder of the sebaceous follicles. Propionibacterium acnes can be involved in inflammatory acne. OBJECTIVES: This case-control study aimed at investigating the occurrence and localization of P. acnes in facial biopsies in acne and to characterize the P. acnes phylotype in skin compartments. METHODS: Specific monoclonal and polyclonal antibodies were applied to skin biopsies of 38 patients with acne and matching controls to localize and characterize P. acnes and to determine expression of co-haemolysin CAMP factor, a putative virulence determinant. RESULTS: Follicular P. acnes was demonstrated in 18 (47%) samples from patients with acne and eight (21%) control samples [odds ratio (OR) 3·37, 95% confidence interval (CI) 1·23-9·23; P = 0·017]. In 14 (37%) samples from patients with acne, P. acnes was visualized in large macrocolonies/biofilms in sebaceous follicles compared with only five (13%) control samples (OR 3·85, 95% CI 1·22-12·14; P = 0·021). Macrocolonies/biofilms consisting of mixed P. acnes phylotypes expressing CAMP1 were detected in both case and control samples. Only four samples tested positive for the presence of Staphylococcus spp. and fungi were not observed. CONCLUSIONS: We have for the first time visualized different P. acnes phylotypes in macrocolonies/biofilms in sebaceous follicles of skin biopsies. Our results support the hypothesis that P. acnes can play a role in the pathogenesis of acne as acne samples showed a higher prevalence of follicular P. acnes colonization, both in terms of follicles containing P. acnes and the greater numbers of bacteria in macrocolonies/biofilms than in control samples.
- 138Leyden, J. J.; Marples, R. R.; Kligman, A. M. Staphylococcus Aureus in the Lesions of Atopic Dermatitis. Br. J. Dermatol. 1974, 90, 525– 530, DOI: 10.1111/j.1365-2133.1974.tb06447.xGoogle Scholar138https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaE2c3mslaitw%253D%253D&md5=f8a00d2a9a9c932ef8a82bb5842e52f8Staphylococcus aureus in the lesions of atopic dermatitisLeyden J J; Marples R R; Kligman A MThe British journal of dermatology (1974), 90 (5), 525-30 ISSN:0007-0963.There is no expanded citation for this reference.
- 139Salava, A.; Lauerma, A. Role of the Skin Microbiome in Atopic Dermatitis. Clin. Transl. Allergy 2014, 4, 33, DOI: 10.1186/2045-7022-4-33Google Scholar139https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXotFWntA%253D%253D&md5=b89224639c8f463e15693707d1acea6bRole of the skin microbiome in atopic dermatitisSalava, Alexander; Lauerma, AnttiClinical and Translational Allergy (2014), 4 (), 33/1-33/6CODEN: CTALAK; ISSN:2045-7022. (BioMed Central Ltd.)Atopic dermatitis (AD) is a common inflammatory skin disorder and characterized by abnormalities in both skin barrier structures and alternations of the immune response. Mol. genetics have dramatically changed our vision of the micro-organisms colonizing the human skin and recently well-documented changes in the skin microbiome in atopic dermatitis have become evident. The microbiome shifts have been primarily documented during disease flares and localized to sites of disease predilection, e.g. folds or facial area. In contrast, active treatment has been assocd. with a recolonisation and higher cutaneous microbial diversity. Addnl. to the known dysfunctions in barrier function of the skin (e.g. filaggrin mutations) and immunol. disturbances (e.g. Th2-shift), evidence is rising that atopic dermatitis is also connected to a dysbiosis of the microbial community without an invading pathogen. In the future the investigation of the patient's skin microbiome may have a foothold in the clinician's diagnostic repertoire and treatment of atopic dermatitis.
- 140Drago, L.; De Grandi, R.; Altomare, G.; Pigatto, P.; Rossi, O.; Toscano, M. Skin Microbiota of First Cousins Affected by Psoriasis and Atopic Dermatitis. Clin. Mol. Allergy 2016, 14, 2, DOI: 10.1186/s12948-016-0038-zGoogle Scholar140https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28nksVOruw%253D%253D&md5=91c49212e45bb35acd8f65ff3869a68aSkin microbiota of first cousins affected by psoriasis and atopic dermatitisDrago Lorenzo; De Grandi Roberta; Altomare Gianfranco; Pigatto Paolo; Rossi Oliviero; Toscano MarcoClinical and molecular allergy : CMA (2016), 14 (), 2 ISSN:1476-7961.BACKGROUND: Psoriasis and atopic dermatitis (AD) are chronic inflammatory skin diseases, which negatively influence the quality of life. In the last years, several evidences highlighted the pivotal role of skin bacteria in worsening the symptomatology of AD and psoriasis. In the present study we evaluated the skin microbiota composition in accurately selected subjects affected by (AD) and psoriasis. METHODS: Three first cousins were chosen for the study according to strict selection of criteria. One subject was affected by moderate AD, one had psoriasis and the last one was included as healthy control. Two lesional skin samples and two non-lesional skin samples (for AD and psoriatic subjects) from an area of 2 cm(2) behind the left ear were withdrawn by mean of a curette. For the healthy control, two skin samples from an area of 2 cm(2) behind the left ear were withdrawn by mean of a curette. DNA was extracted and sequencing was completed on the Ion Torrent PGM platform. Culturing of Staphylococcus aureus from skin samples was also performed. RESULTS: The psoriatic subject showed a decrease in Firmicutes abundance and an increase in Proteobacteria abundance. Moreover, an increase in Streptococcaceae, Rhodobacteraceae, Campylobacteraceae and Moraxellaceae has been observed in psoriatic subject, if compared with AD individual and control. Finally, AD individual showed a larger abundance of S. aureus than psoriatic and healthy subjects. Moreover, the microbiota composition of non-lesional skin samples belonging to AD and psoriatic individuals was very similar to the bacterial composition of skin sample belonging to the healthy control. CONCLUSION: Significant differences between the skin microbiota of psoriatic individual and healthy and AD subjects were observed.
- 141Gonzalez, M. E.; Schaffer, J. V.; Orlow, S. J.; Gao, Z.; Li, H.; Alekseyenko, A. V.; Blaser, M. J. Cutaneous Microbiome Effects of Fluticasone Propionate Cream and Adjunctive Bleach Baths in Childhood Atopic Dermatitis. J. Am. Acad. Dermatol. 2016, 75, 481– 493, DOI: 10.1016/j.jaad.2016.04.066Google Scholar141https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtlOqsr%252FI&md5=04490c4954f0e517c4b1f6e083dbefd7Cutaneous microbiome effects of fluticasone propionate cream and adjunctive bleach baths in childhood atopic dermatitisGonzalez, Mercedes E.; Schaffer, Julie V.; Orlow, Seth J.; Gao, Zhan; Li, Huilin; Alekseyenko, Alexander V.; Blaser, Martin J.Journal of the American Academy of Dermatology (2016), 75 (3), 481-493.e8CODEN: JAADDB; ISSN:0190-9622. (Elsevier)Patients with atopic dermatitis (AD) are prone to skin infections, with microbes such as Staphylococcus aureus suspected of contributing to pathogenesis. Bleach baths might improve AD by reducing skin microbial burden. We sought to characterize the microbiota of lesional and nonlesional skin in young children with AD and control subjects and compare changes after treatment with a topical corticosteroid (TCS) alone or TCS + dil. bleach bath. In a randomized, placebo-controlled, single-blinded clin. trial in 21 children with AD and 14 healthy children, lesional and nonlesional AD skin was examd. at baseline and after 4-wk treatment with TCS alone or TCS plus bleach bath. Microbial DNA was extd. for quant. polymerase chain reaction of predominant genera and 16S rRNA sequencing. At baseline, densities of total bacteria and Staphylococcus, including Staphylococcus aureus, were significantly higher at the worst AD lesional site than nonlesional (P = .001) or control (P < .001) skin; bacterial communities on lesional and nonlesional AD skin significantly differed from each other (P = .04) and from control (P < .001). After TCS + bleach bath or TCS alone, bacterial compns. on lesional skin normalized (P < .0001), resembling nonlesional skin, with microbial diversity restored to control skin levels. The 4-wk time period and/or the twice-weekly baths may not have been sufficient for addnl. impact on the cutaneous microbiome. More detailed sequencing may allow better characterization of the distinguishing taxa with bleach bath treatment. Treatment with a TCS cream suffices to normalize the cutaneous microbiota on lesional AD; after treatment, bacterial communities on lesional skin resemble nonlesional skin but remain distinct from control.
- 142Zasloff, M. Antimicrobial Peptides, Innate Immunity, and the Normally Sterile Urinary Tract. J. Am. Soc. Nephrol. 2007, 18, 2810– 2816, DOI: 10.1681/ASN.2007050611Google Scholar142https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtlGgsbrO&md5=cde3d3117e4fb7cd7788fe7cc8a195b4Antimicrobial peptides, innate immunity, and the normally sterile urinary tractZasloff, MichaelJournal of the American Society of Nephrology (2007), 18 (11), 2810-2816CODEN: JASNEU; ISSN:1046-6673. (American Society of Nephrology)A review. Considering the anatomical location of the urethral meatus, it is surprising that urine is normally sterile. The defensive properties of uroepithelia help maintain this sterility as strategically necessary for long-term survival. Epithelia lining the urinary tract prevent adhesion of bacteria by release of Tamm-Horsfall protein, lactoferrin, lipocalin, and constitutive and inducible bactericidal antimicrobial peptides such as α- and β-defensins and cathelicidin. Microbes that overwhelm these early defenses contact uroepithelia and activate an innate immune response through Toll-like receptor 4. With persistence of increasing nos. of microbes, chemokines (IL-8) and cytokines (IL-1 and TNFα) attract and activate large nos. of neutrophils and macrophages that damage tubulointerstitial parenchyma. The risk of serious infection in humans seems quite variable. Cathelicidin, for example, is a vitamin D-dependent gene, and vitamin D stores may influence susceptibility to urinary tract infection in selected individuals. As more knowledge accrues, vitamin D supplementation may someday be useful as adjuvant therapy in this setting.
- 143Wolfe, A. J.; Brubaker, L. “Sterile Urine” and the Presence of Bacteria. Eur. Urol. 2015, 68, 173– 174, DOI: 10.1016/j.eururo.2015.02.041