title: Colonization-induced host-gut microbial metabolic interaction.
abstract: The gut microbiota enhances the host's metabolic capacity for processing nutrients and drugs and modulate the activities of multiple pathways in a variety of organ systems. We have probed the systemic metabolic adaptation to gut colonization for 20 days following exposure of axenic mice (n = 35) to a typical environmental microbial background using high-resolution (1)H nuclear magnetic resonance (NMR) spectroscopy to analyze urine, plasma, liver, kidney, and colon (5 time points) metabolic profiles. Acquisition of the gut microbiota was associated with rapid increase in body weight (4%) over the first 5 days of colonization with parallel changes in multiple pathways in all compartments analyzed. The colonization process stimulated glycogenesis in the liver prior to triggering increases in hepatic triglyceride synthesis. These changes were associated with modifications of hepatic Cyp8b1 expression and the subsequent alteration of bile acid metabolites, including taurocholate and tauromuricholate, which are essential regulators of lipid absorption. Expression and activity of major drug-metabolizing enzymes (Cyp3a11 and Cyp2c29) were also significantly stimulated. Remarkably, statistical modeling of the interactions between hepatic metabolic profiles and microbial composition analyzed by 16S rRNA gene pyrosequencing revealed strong associations of the Coriobacteriaceae family with both the hepatic triglyceride, glucose, and glycogen levels and the metabolism of xenobiotics. These data demonstrate the importance of microbial activity in metabolic phenotype development, indicating that microbiota manipulation is a useful tool for beneficially modulating xenobiotic metabolism and pharmacokinetics in personalized health care.
  
  
  OBJECTIVE
  Gut bacteria have been associated with various essential biological functions in humans such as energy harvest and regulation of blood pressure. Furthermore, gut microbial colonization occurs after birth in parallel with other critical processes such as immune and cognitive development. Thus, it is essential to understand the bidirectional interaction between the host metabolism and its symbionts. Here, we describe the first evidence of an in vivo association between a family of bacteria and hepatic lipid metabolism. These results provide new insights into the fundamental mechanisms that regulate host-gut microbiota interactions and are thus of wide interest to microbiological, nutrition, metabolic, systems biology, and pharmaceutical research communities. This work will also contribute to developing novel strategies in the alteration of host-gut microbiota relationships which can in turn beneficially modulate the host metabolism.
authors.affiliation: Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom. sclaus@imperial.ac.uk
authors.forename: Sandrine P
authors.initials: SP
authors.lastname: Claus
authors.forename: Sandrine L
authors.initials: SL
authors.lastname: Ellero
authors.forename: Bernard
authors.initials: B
authors.lastname: Berger
authors.forename: Lutz
authors.initials: L
authors.lastname: Krause
authors.forename: Anne
authors.initials: A
authors.lastname: Bruttin
authors.forename: Jérôme
authors.initials: J
authors.lastname: Molina
authors.forename: Alain
authors.initials: A
authors.lastname: Paris
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Want
authors.forename: Isabelle
authors.initials: I
authors.lastname: de Waziers
authors.forename: Olivier
authors.initials: O
authors.lastname: Cloarec
authors.forename: Selena E
authors.initials: SE
authors.lastname: Richards
authors.forename: Yulan
authors.initials: Y
authors.lastname: Wang
authors.forename: Marc-Emmanuel
authors.initials: ME
authors.lastname: Dumas
authors.forename: Alastair
authors.initials: A
authors.lastname: Ross
authors.forename: Serge
authors.initials: S
authors.lastname: Rezzi
authors.forename: Sunil
authors.initials: S
authors.lastname: Kochhar
authors.forename: Peter
authors.initials: P
authors.lastname: Van Bladeren
authors.forename: John C
authors.initials: JC
authors.lastname: Lindon
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
mesh_terms: D000818:Animals; D001419:Bacteria / Q000145:classification / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D044822:Biodiversity; D001835:Body Weight; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004275:DNA, Ribosomal / Q000737:chemistry / Q000235:genetics; D005260:Female; D041981:Gastrointestinal Tract / Q000737:chemistry / Q000378:metabolism / Q000382:microbiology* / Q000502:physiology*; D005856:Germ-Free Life; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010949:Plasma / Q000737:chemistry; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA; D014556:Urine / Q000737:chemistry
chemical_list: D004269:DNA, Bacterial; D004275:DNA, Ribosomal; D012336:RNA, Ribosomal, 16S