Regulation of Antibacterial Defense in the Small Intestine by the Nuclear Bile Acid Receptor

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 Feb 14

PMID 16473946

Citations 519

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

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