Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1073/pnas.0601056103

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

15/08/2006

Volume

103

Pages

12511 - 12516

Keywords

Animals, Body Weight, Dietary Fats, Fatty Liver, Gastrointestinal Tract, Glucose, Homeostasis, Insulin, Insulin Resistance, Lipids, Liver, Male, Methylamines, Mice, Mice, Inbred BALB C, Multivariate Analysis, Nuclear Magnetic Resonance, Biomolecular, Phenotype