Emerging roles of bile acids in mucosal immunity and inflammation

Abstract

Bile acids are cholesterol-derived surfactants that circulate actively between the liver and ileum and that are classically recognized for emulsifying dietary lipids to facilitate absorption. More recent studies, however, have revealed new functions of bile acids; as pleotropic signaling metabolites that regulate diverse metabolic and inflammatory pathways in multiple cell types and tissues through dynamic interactions with both germline-encoded host receptors and the microbiota. Accordingly, perturbed bile acid circulation and/or metabolism is now implicated in the pathogenesis of cholestatic liver diseases, metabolic syndrome, colon cancer, and inflammatory bowel diseases (IBDs). Here, we discuss the three-dimensional interplay between bile acids, the microbiota, and the mucosal immune system, focusing on the mechanisms that regulate intestinal homeostasis and inflammation. Although the functions of bile acids in mucosal immune regulation are only beginning to be appreciated, targeting bile acids and their cellular receptors has already proven an important area of new drug discovery.

Gut microbiome dysbiosis is associated with elevated toxic bile acids in Parkinson’s disease

“…XIVa and XI of the Firmicutes phylum (Wahlström et al, 2016). LCA and DCA are hydrophobic bile acids that are cytotoxic at elevated physiological concentrations (Chen et al, 2019a;Pavlidis et al, 2015). LCA, the most toxic bile acid, is highly insoluble, which limits its reabsorption, and it is primarily excreted in stool.…”

MAIT cell activation in adolescents is impacted by bile acid concentrations and body weight

“…The BAs are mainly (95%) reabsorbed in the distal ileum and returned to the liver by the enterohepatic circulation . A minor fraction of BAs escapes the enterohepatic circulation and reaches the systemic circulation where they regulate many processes, including lipid and glucose homeostasis, intestinal motility, inflammation and configuration and growth of the gut microbiome . A direct impact of BAs on the function of innate immune cells such as monocytes, macrophages and granulocytes has been reported .…”

Emerging therapies in primary sclerosing cholangitis: pathophysiological basis and clinical opportunities

“…Another fundamental question is whether observed alterations in the gut microbiota serve causal roles in the development of PSC or occur secondary to the ongoing disease processes, or both. The gut microbiota certainly holds strong co-metabolic functions in bile acid homeostasis [46,128], and may influence bile physiology either directly or indirectly (e.g. via altered FXR signaling).…”