title: The footprints of gut microbial-mammalian co-metabolism.
abstract: 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.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China.
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Zheng
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Xie
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhao
authors.forename: Linjing
authors.initials: L
authors.lastname: Zhao
authors.forename: Chun
authors.initials: C
authors.lastname: Yao
authors.forename: Norman H L
authors.initials: NH
authors.lastname: Chiu
authors.forename: Zhanxiang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Bao
authors.forename: Weiping
authors.initials: W
authors.lastname: Jia
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
mesh_terms: D000818:Animals; D001419:Bacteria / Q000737:chemistry / Q000254:growth & development*; D050260:Carbohydrate Metabolism; D002853:Chromatography, Liquid / Q000379:methods; D015377:Cilastatin / Q000494:pharmacology; D005243:Feces / Q000737:chemistry*; D008401:Gas Chromatography-Mass Spectrometry; D041981:Gastrointestinal Tract / Q000737:chemistry / Q000378:metabolism* / Q000382:microbiology; D015378:Imipenem / Q000494:pharmacology; D008297:Male; D008322:Mammals; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D054892:Metagenome; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014556:Urine / Q000737:chemistry*
chemical_list: D015377:Cilastatin; D015378:Imipenem