title: Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice.
abstract: Here, we study the intricate relationship between gut microbiota and host cometabolic phenotypes associated with dietary-induced impaired glucose homeostasis and nonalcoholic fatty liver disease (NAFLD) in a mouse strain (129S6) known to be susceptible to these disease traits, using plasma and urine metabotyping, achieved by (1)H NMR spectroscopy. Multivariate statistical modeling of the spectra shows that the genetic predisposition of the 129S6 mouse to impaired glucose homeostasis and NAFLD is associated with disruptions of choline metabolism, i.e., low circulating levels of plasma phosphatidylcholine and high urinary excretion of methylamines (dimethylamine, trimethylamine, and trimethylamine-N-oxide), coprocessed by symbiotic gut microbiota and mammalian enzyme systems. Conversion of choline into methylamines by microbiota in strain 129S6 on a high-fat diet reduces the bioavailability of choline and mimics the effect of choline-deficient diets, causing NAFLD. These data also indicate that gut microbiota may play an active role in the development of insulin resistance.
authors.affiliation: Department of Biological Chemistry, Imperial College London, South Kensington, London SW7 2AZ, United Kingdom.
authors.forename: Marc-Emmanuel
authors.initials: ME
authors.lastname: Dumas
authors.forename: Richard H
authors.initials: RH
authors.lastname: Barton
authors.forename: Ayo
authors.initials: A
authors.lastname: Toye
authors.forename: Olivier
authors.initials: O
authors.lastname: Cloarec
authors.forename: Christine
authors.initials: C
authors.lastname: Blancher
authors.forename: Alice
authors.initials: A
authors.lastname: Rothwell
authors.forename: Jane
authors.initials: J
authors.lastname: Fearnside
authors.forename: Roger
authors.initials: R
authors.lastname: Tatoud
authors.forename: Véronique
authors.initials: V
authors.lastname: Blanc
authors.forename: John C
authors.initials: JC
authors.lastname: Lindon
authors.forename: Steve C
authors.initials: SC
authors.lastname: Mitchell
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: James
authors.initials: J
authors.lastname: Scott
authors.forename: Dominique
authors.initials: D
authors.lastname: Gauguier
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
mesh_terms: D000818:Animals; D001835:Body Weight; D004041:Dietary Fats; D005234:Fatty Liver / Q000503:physiopathology*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism; D008297:Male; D008744:Methylamines / Q000097:blood / Q000652:urine; D051379:Mice; D008807:Mice, Inbred BALB C; D015999:Multivariate Analysis; D019906:Nuclear Magnetic Resonance, Biomolecular; D010641:Phenotype
chemical_list: D004041:Dietary Fats; D007328:Insulin; D008055:Lipids; D008744:Methylamines; D005947:Glucose