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The Footprints of Gut Microbial–Mammalian Co-Metabolism

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School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, P. R. China
Department of Nutrition, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, North Carolina 28081, United States
§ Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina 27402, United States
Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center of Diabetes, Shanghai 200233, P. R. China
Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London SW7 2AZ, United Kingdom
Wei Jia, Department of Nutrition, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, North Carolina 28081. Phone: 1-704-250-5803. Fax: 1-704-250-5809. E-mail: [email protected]. Weiping Jia, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai 200233, China. Tel: +86-21-6436-9181. Fax: +86-21-6436-8031. E-mail: [email protected]
Cite this: J. Proteome Res. 2011, 10, 12, 5512–5522
Publication Date (Web):October 4, 2011
Copyright © 2011 American Chemical Society

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    Gut microbiota are associated with essential various biological functions in humans through a “network” of microbial–host co-metabolism to process nutrients and drugs and modulate the activities of multiple pathways in organ systems that are linked to different diseases. The microbiome impacts strongly on the metabolic phenotypes of the host, and hence, metabolic readouts can give insights into functional metagenomic activity. We applied an untargeted mass spectrometry (MS) based metabonomics approach to profile normal Wistar rats exposed to a broad spectrum β-lactam antibiotic imipenem/cilastatin sodium, at 50 mg/kg/daily for 4 days followed by a 14-day recovery period. In-depth metabolic phenotyping allowed identification of a panel of 202 urinary and 223 fecal metabolites significantly related to end points of a functional metagenome (p < 0.05 in at least one day), many of which have not been previously reported such as oligopeptides and carbohydrates. This study shows extensive gut microbiota modulation of host systemic metabolism involving short-chain fatty acids, tryptophan, tyrosine metabolism, and possibly a compensatory mechanism of indole–melatonin production. Given the integral nature of the mammalian genome and metagenome, this panel of metabolites will provide a new platform for potential therapeutic markers and mechanistic solutions to complex problems commonly encountered in pathology, toxicology, or drug metabolism studies.

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    Procedure of urine and feces samples preparation; LC–MS and GC–MS profiling methods; trajectories of different data sets from urine and feces analyzed by LC–MS and GC–MS; heat-maps of all differential metabolites derived in urine and feces; Overview of related metabolites in the whole mammalian metabolome; all of the urinary and fecal metabolites associated with gut microbial–mammalian co-metabolism. This material is available free of charge via the Internet at

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