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
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Online Access:https://doi.org/10.1038/msb4100153
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author 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
author_facet 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
author_sort François‐Pierre J Martin
collection DOAJ
description 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.
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spelling doaj-art-d4a727dab6a644aead2f16d07d03fcc12025-08-24T12:01:50ZengSpringer NatureMolecular Systems Biology1744-42922007-05-013111610.1038/msb4100153A top‐down systems biology view of microbiome‐mammalian metabolic interactions in a mouse modelFrançois‐Pierre J Martin0Marc‐Emmanuel Dumas1Yulan Wang2Cristina Legido‐Quigley3Ivan K S Yap4Huiru Tang5Séverine Zirah6Gerard M Murphy7Olivier Cloarec8John C Lindon9Norbert Sprenger10Laurent B Fay11Sunil Kochhar12Peter van Bladeren13Elaine Holmes14Jeremy K Nicholson15Department of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Imperial College LondonDepartment of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Imperial College LondonDepartment of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Imperial College LondonDepartment of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Imperial College LondonDepartment of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Imperial College LondonDepartment of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Imperial College LondonDepartment of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Imperial College LondonDepartment of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Imperial College LondonDepartment of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Imperial College LondonDepartment of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Imperial College LondonNestlé Research CenterNestlé Research CenterNestlé Research CenterNestlé Research CenterDepartment of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Imperial College LondonDepartment of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Imperial College LondonAbstract 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.https://doi.org/10.1038/msb4100153co‐metabolismgut microflorametabonomics/metabolomicsnetwork modelingsystems biology
spellingShingle 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
A top‐down systems biology view of microbiome‐mammalian metabolic interactions in a mouse model
Molecular Systems Biology
co‐metabolism
gut microflora
metabonomics/metabolomics
network modeling
systems biology
title A top‐down systems biology view of microbiome‐mammalian metabolic interactions in a mouse model
title_full A top‐down systems biology view of microbiome‐mammalian metabolic interactions in a mouse model
title_fullStr A top‐down systems biology view of microbiome‐mammalian metabolic interactions in a mouse model
title_full_unstemmed A top‐down systems biology view of microbiome‐mammalian metabolic interactions in a mouse model
title_short A top‐down systems biology view of microbiome‐mammalian metabolic interactions in a mouse model
title_sort top down systems biology view of microbiome mammalian metabolic interactions in a mouse model
topic co‐metabolism
gut microflora
metabonomics/metabolomics
network modeling
systems biology
url https://doi.org/10.1038/msb4100153
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