title: 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 a normal flora to conventional mice. We perform parallel microbiological profiling, metabolic profiling by (1)H 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.
authors.affiliation: Department of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Imperial College London, South Kensington, London, UK.
authors.forename: François-Pierre J
authors.initials: FP
authors.lastname: Martin
authors.forename: Marc-Emmanuel
authors.initials: ME
authors.lastname: Dumas
authors.forename: Yulan
authors.initials: Y
authors.lastname: Wang
authors.forename: Cristina
authors.initials: C
authors.lastname: Legido-Quigley
authors.forename: Ivan K S
authors.initials: IK
authors.lastname: Yap
authors.forename: Huiru
authors.initials: H
authors.lastname: Tang
authors.forename: Séverine
authors.initials: S
authors.lastname: Zirah
authors.forename: Gerard M
authors.initials: GM
authors.lastname: Murphy
authors.forename: Olivier
authors.initials: O
authors.lastname: Cloarec
authors.forename: John C
authors.initials: JC
authors.lastname: Lindon
authors.forename: Norbert
authors.initials: N
authors.lastname: Sprenger
authors.forename: Laurent B
authors.initials: LB
authors.lastname: Fay
authors.forename: Sunil
authors.initials: S
authors.lastname: Kochhar
authors.forename: Peter
authors.initials: P
authors.lastname: van Bladeren
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
mesh_terms: D000465:Algorithms; D000818:Animals; D001647:Bile Acids and Salts / Q000032:analysis / Q000096:biosynthesis / Q000737:chemistry; D002853:Chromatography, Liquid; D015169:Colony Count, Microbial; D005232:Fatty Acids, Volatile / Q000032:analysis; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D005260:Female; D041981:Gastrointestinal Tract / Q000737:chemistry / Q000378:metabolism* / Q000382:microbiology*; D006790:Host-Parasite Interactions; D006801:Humans; D007082:Ileum / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D023421:Models, Animal; D009928:Organ Specificity; D049490:Systems Biology
chemical_list: D001647:Bile Acids and Salts; D005232:Fatty Acids, Volatile