A top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse model.
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.
Martin
François-Pierre J
FP
Department of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Imperial College London, South Kensington, London, UK.
Dumas
Marc-Emmanuel
ME
Wang
Yulan
Y
Legido-Quigley
Cristina
C
Yap
Ivan K S
IK
Tang
Huiru
H
Zirah
Séverine
S
Murphy
Gerard M
GM
Cloarec
Olivier
O
Lindon
John C
JC
Sprenger
Norbert
N
Fay
Laurent B
LB
Kochhar
Sunil
S
van Bladeren
Peter
P
Holmes
Elaine
E
Nicholson
Jeremy K
JK
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
D001647:Bile Acids and Salts; D005232:Fatty Acids, Volatile