Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites

Proceedings of the National Academy of Sciences of the United States of America - Tập 106 Số 10 - Trang 3698-3703 - 2009
William R. Wikoff1, Andrew Anfora2, Jun Liu2, Peter G. Schultz2, Scott A. Lesley2, Eric C. Peters2, Gary Siuzdak1
1Department of Molecular Biology and Center for Mass Spectrometry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; and
2Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121

Tóm tắt

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 ≈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.

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Tài liệu tham khảo

10.1126/science.1104816

10.1016/j.chom.2008.02.015

10.1016/j.cell.2005.05.007

10.1073/pnas.0601056103

10.1128/IAI.72.9.4996-5003.2004

10.1194/jlr.R500013-JLR200

10.1189/jlb.0607372

10.1073/pnas.0706625104

10.1038/nature06244

10.1038/nature05414

10.1038/ismej.2007.3

10.1146/annurev.nutr.28.061807.155402

10.1126/science.1124234

10.1073/pnas.0804437105

10.1073/pnas.0404878101

10.1021/pr060596a

10.1021/pr700864x

10.1038/msb.2008.56

10.1021/pr060505

10.1021/ac701982e

10.1021/ac051312t

10.1021/ac051437y

10.1128/jb.109.1.74-80.1972

10.1007/s10350-006-0763-3

10.1046/j.1523-1755.2002.00318.x

10.1053/ajkd.2003.50104

10.1007/s002489900020

10.1002/1097-4644(20010601)81:3<507::AID-JCB1064>3.0.CO;2-M

10.1074/jbc.274.31.21937

10.1007/s12031-002-0036-0

10.1007/BF00425340

10.1111/j.1471-4159.1980.tb09944.x

10.1111/j.1365-2672.1996.tb04331.x

10.1093/ajcn/29.12.1448

10.1007/s00216-006-0495-1

10.1016/S0021-9673(00)84769-X

10.1093/jjco/hyh015

10.1128/AEM.71.1.214-219.2005

10.1079/BJN20051565

M Chiba, K Poon, J Hollands, KS Pang, Glycine conjugation activity of benzoic acid and its acinar localization in the perfused rat liver. J Pharmacol Exp Ther 268, 409–416 (1994).

10.1002/jps.2600600227

K Poon, KS Pang, Benzoic acid glycine conjugation in the isolated perfused rat kidney. Drug Metab Dispos 23, 255–260 (1995).

10.3181/00379727-90-22134

10.1203/00006450-199005000-00017

P Rinaldo, JJ O'Shea, RD Welch, K Tanaka, Diagnosis of medium chain acyl-CoA dehydrogenase deficiency by stable isotope dilution analysis of urinary acylglycines: Retrospective and prospective studies, and comparison of its accuracy to acylcarnitine identification by FAB/mass spectrometry. Prog Clin Biol Res 321, 411–418 (1990).

10.1016/0009-8981(88)90250-1

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Proceedings of the National Academy of Sciences of the United States of America

Tập 106 Số 10

3698-3703

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