Bile acids, bile pigments and colorectal cancer risk.

Abstract

The gut microbial co-metabolism of bile-derived compounds (e.g. bile acids and bile pigments) affects colorectal cancer (CRC) risk. Here, we review recent findings with focus on selected novel aspects of bile-associated effects with interesting but unclear implications on CRC risk. Numerous studies demonstrated novel biotransformation of bile acids by gut bacteria (e.g. microbial conjugation of bile acids), resulting in diverse bile acid compounds that show complex interactions with host receptors (e.g. FXR, TGR5). In addition, YAP-associated signalling in intestinal epithelial cells is modulated via bile acid receptor TGR5 and contributes to colonic tumorigenesis. Finally, studies indicate that serum levels of the bile pigment bilirubin are inversely associated with CRC risk or intestinal inflammation and that bilirubin affects gut microbiota composition. Bile acids and bile pigments have multiple effects on intestinal microbe-host interactions, which may collectively modulate long-term CRC risk of the host.