Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice

Marc Emmanuel Dumas, Richard H. Barton, Ayo Toye, Olivier Cloarec, Christine Blancher, Alice Rothwell, Jane Fearnside, Roger Tatoud, Véronique Blanc, John C. Lindon, Steve C. Mitchell, Elaine Holmes, Mark I. McCarthy, James Scott, Dominique Gauguier, Jeremy K. Nicholson

Research output: Contribution to journalArticlepeer-review

848 Scopus citations

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 1H 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.

Original languageEnglish
Pages (from-to)12511-12516
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number33
DOIs
StatePublished - Aug 15 2006

Keywords

  • Metabolic syndrome
  • Metabonomics NMR
  • Nonalcoholic fatty liver disease
  • Nutritional genomics

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