Endoplasmic reticulum stress in intestinal inflammation: implications of bile acids

Apart from their commonly known, almost exclusive role in nutrient absorption and cholesterol homeostasis, there is now empirical evidence to suggest that bile acids exert pleiotropic effects on the host immune system. Here, bile acids serve as ligands for various evolutionarily conserved nuclear hormone and G-protein-coupled receptors. The wide distribution of these bile acid-activated receptors among tissues and cells, especially the immune cells of the intestine, facilitates the influence of bile acids on host gut immune responses. Concurrently, these immune cells are bound to experience endoplasmic reticulum (ER) stress due to dynamic cellular functions, resulting in the activation of a salvage pathway, the unfolded protein response (UPR). Severely dysregulated ER stress signaling cascade is found to be associated with many debilitating inflammatory disorders. Finally, there is growing evidence of the interplay between bile acids and ER stress signaling pathways gearing towards inflammation-driven intestinal disorders. This review expounds on the enigmatic networking of the triad: bile acids, ER stress and inflammation—emphasizing on molecular players of the signaling cascades involving the trio, which may offer a promising therapeutic approach for inflammation-driven disorders in the intestine.