Metabolic Profiling Reveals a Contribution of Gut Microbiota to Fatty Liver Phenotype in Insulin-resistant Mice

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 Aug 10

PMID 16895997

Citations 423

Authors

Marc-Emmanuel Dumas

Richard H Barton

Ayo Toye

Olivier Cloarec

Christine Blancher

Alice Rothwell

Jane Fearnside

Roger Tatoud

Veronique Blanc

John C Lindon

Steve C Mitchell

Elaine Holmes

Mark I McCarthy

James Scott

Dominique Gauguier

Jeremy K Nicholson

Affiliations

Soon will be listed here.

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.

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