A top‐down systems biology view of microbiome‐mammalian metabolic interactions in a mouse model

A top‐down systems biology view of microbiome‐mammalian metabolic interactions in a mouse model

Abstract Symbiotic gut microorganisms (microbiome) interact closely with the mammalian host's metabolism and are important determinants of human health. Here, we decipher the complex metabolic effects of microbial manipulation, by comparing germfree mice colonized by a human baby flora (HBF) or...

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Main Authors: François‐Pierre J Martin, Marc‐Emmanuel Dumas, Yulan Wang, Cristina Legido‐Quigley, Ivan K S Yap, Huiru Tang, Séverine Zirah, Gerard M Murphy, Olivier Cloarec, John C Lindon, Norbert Sprenger, Laurent B Fay, Sunil Kochhar, Peter van Bladeren, Elaine Holmes, Jeremy K Nicholson
Format: Article
Language:English
Published: Springer Nature 2007-05-01
Series:Molecular Systems Biology
Subjects:
co‐metabolism
gut microflora
metabonomics/metabolomics
network modeling
systems biology
Online Access:https://doi.org/10.1038/msb4100153
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Summary:Abstract Symbiotic gut microorganisms (microbiome) interact closely with the mammalian host's metabolism and are important determinants of human health. Here, we decipher the complex metabolic effects of microbial manipulation, by comparing germfree mice colonized by a human baby flora (HBF) or a normal flora to conventional mice. We perform parallel microbiological profiling, metabolic profiling by 1H nuclear magnetic resonance of liver, plasma, urine and ileal flushes, and targeted profiling of bile acids by ultra performance liquid chromatography–mass spectrometry and short‐chain fatty acids in cecum by GC‐FID. Top‐down multivariate analysis of metabolic profiles reveals a significant association of specific metabotypes with the resident microbiome. We derive a transgenomic graph model showing that HBF flora has a remarkably simple microbiome/metabolome correlation network, impacting directly on the host's ability to metabolize lipids: HBF mice present higher ileal concentrations of tauro‐conjugated bile acids, reduced plasma levels of lipoproteins but higher hepatic triglyceride content associated with depletion of glutathione. These data indicate that the microbiome modulates absorption, storage and the energy harvest from the diet at the systems level.
ISSN:1744-4292

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