Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor

Takeshi Inagaki, Antonio Moschetta, Youn Kyoung Lee, Li Peng, Guixiang Zhao, Michael Downes, Ruth T. Yu, John M. Shelton, James A. Richardson, Joyce J. Repa, David J. Mangelsdorf, Steven A. Kliewer

Research output: Contribution to journalArticlepeer-review

560 Scopus citations

Abstract

Obstruction of bile flow results in bacterial proliferation and mucosal injury in the small intestine that can lead to the translocation of bacteria across the epithelial barrier and systemic infection. These adverse effects of biliary obstruction can be inhibited by administration of bile acids. Here we show that the farnesoid X receptor (FXR), a nuclear receptor for bile acids, induces genes involved in enteroprotection and inhibits bacterial overgrowth and mucosal injury in ileum caused by bile duct ligation. Mice lacking FXR have increased ileal levels of bacteria and a compromised epithelial barrier. These findings reveal a central role for FXR in protecting the distal small intestine from bacterial invasion and suggest that FXR agonists may prevent epithelial deterioration and bacterial translocation in patients with impaired bile flow.

Original languageEnglish (US)
Pages (from-to)3920-3925
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number10
DOIs
StatePublished - Mar 7 2006

Keywords

  • Bacteria
  • Barrier
  • Biliary obstruction
  • Epithelial
  • Ileum

ASJC Scopus subject areas

  • General

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