Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist

  • Sayin S
  • Wahlström A
  • Felin J
 et al. 
  • 472

    Readers

    Mendeley users who have this article in their library.
  • 460

    Citations

    Citations of this article.

Abstract

Bile acids are synthesized from cholesterol in the liver and further metabolized by the gut microbiota into secondary bile acids. Bile acid synthesis is under negative feedback control through activation of the nuclear receptor farnesoid X receptor (FXR) in the ileum and liver. Here we profiled the bile acid composition throughout the enterohepatic system in germ-free (GF) and conventionally raised (CONV-R) mice. We confirmed a dramatic reduction in muricholic acid, but not cholic acid, levels in CONV-R mice. Rederivation of Fxr-deficient mice as GF demonstrated that the gut microbiota regulated expression of fibroblast growth factor 15 in the ileum and cholesterol 7α-hydroxylase (CYP7A1) in the liver by FXR-dependent mechanisms. Importantly, we identified tauro-conjugated beta- and alpha-muricholic acids as FXR antagonists. These studies suggest that the gut microbiota not only regulates secondary bile acid metabolism but also inhibits bile acid synthesis in the liver by alleviating FXR inhibition in the ileum. © 2013 Elsevier Inc.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Get full text

Authors

  • Matej OresicTurku Centre for Biotechnology

    Follow
  • Sama I. Sayin

  • Annika Wahlström

  • Jenny Felin

  • Sirkku Jäntti

  • Hanns Ulrich Marschall

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free