Document Detail


Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites.
MedLine Citation:
PMID:  19234110     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although it has long been recognized that the enteric community of bacteria that inhabit the human distal intestinal track broadly impacts human health, the biochemical details that underlie these effects remain largely undefined. Here, we report a broad MS-based metabolomics study that demonstrates a surprisingly large effect of the gut "microbiome" on mammalian blood metabolites. Plasma extracts from germ-free mice were compared with samples from conventional (conv) animals by using various MS-based methods. Hundreds of features were detected in only 1 sample set, with the majority of these being unique to the conv animals, whereas approximately 10% of all features observed in both sample sets showed significant changes in their relative signal intensity. Amino acid metabolites were particularly affected. For example, the bacterial-mediated production of bioactive indole-containing metabolites derived from tryptophan such as indoxyl sulfate and the antioxidant indole-3-propionic acid (IPA) was impacted. Production of IPA was shown to be completely dependent on the presence of gut microflora and could be established by colonization with the bacterium Clostridium sporogenes. Multiple organic acids containing phenyl groups were also greatly increased in the presence of gut microbes. A broad, drug-like phase II metabolic response of the host to metabolites generated by the microbiome was observed, suggesting that the gut microflora has a direct impact on the drug metabolism capacity of the host. Together, these results suggest a significant interplay between bacterial and mammalian metabolism.
Authors:
William R Wikoff; Andrew T Anfora; Jun Liu; Peter G Schultz; Scott A Lesley; Eric C Peters; Gary Siuzdak
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-02-20
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  106     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-03-11     Completed Date:  2009-03-26     Revised Date:  2010-09-23    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3698-703     Citation Subset:  IM    
Affiliation:
Department of Molecular Biology and Center for Mass Spectrometry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bacteria / metabolism*
Blood / metabolism*
Gastrointestinal Tract / microbiology*
Host-Pathogen Interactions
Humans
Indoles / blood,  chemistry
Mammals
Mass Spectrometry
Metabolomics*
Metagenome
Sulfur / metabolism
Chemical
Reg. No./Substance:
0/Indoles; 7704-34-9/Sulfur
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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