Crosstalk between bile acid-activated receptors and microbiome in entero-hepatic inflammation

Abstract

Bile acids are potent signaling molecules exerting diverse actions through bile acid-activated receptors. Among them, the Farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 (TGR5; GPBAR1), modulate the inflammation occurring in chronic/acute hepatitis, cholestasis, and inflammatory bowel disease. A role for other bile acid-responsive receptors in this context is emerging. This review aims to summarize recent advances on the immune-modulatory actions of the bile acid-responsive receptors Shingosine-1-phosphate receptor 2 (S1PR2), pregnane X receptor (PXR), constitutive androstane receptor (CAR), vitamin D receptor (VDR), and retinoic acid-related orphan receptor γt (RORγt). How microbiota-derived bile acids contribute to intestinal and hepatic inflammation, potentially through these receptors, is also discussed. These concepts pave the way to novel and innovative strategies aiming at modulating the gut microbiota to tackle inflammatory syndromes.

Keywords: bile acids; cholestatic disease; gut microbiota; inflammatory bowel disease; intestinal inflammation; microbial metabolism.