Once known exclusively for their role in nutrients absorption, bile acids have emerged as signaling molecules, generated from cholesterol breakdown, acting on several immune cells by activating a variety of receptors including the G protein-coupled bile acid receptor 1 (GPABR1 or TGR5), the Farnesoid-X-receptor (FXR) and, as recently discovered, the retinoid-related orphan receptors (ROR)γt. GPBAR1, FXR, and RORγt are highly expressed in cells of the innate and adaptive immune system (i.e., dendritic cells (DCs), macrophages, innate lymphoid 3 cells (ILC3s), and T helper 17 (Th17) lymphocytes) and plays an important role in regulating intestinal and liver immunity, highlighting a role for various bile acid species in regulating immune responses to intestinal microbial antigens. While primary bile acids are generated from the cholesterol breakdown secondary bile acids, the GPBAR1 ligands, and oxo-bile acids derivatives, the RORγt ligands, are generated by the intestinal microbiota, highlighting the potential of these bile acids in mediating the chemical communication between the intestinal microbiota and the host. Changes in intestinal microbiota, dysbiosis, alter the composition of the bile acid pool, promoting the activation of the immune system and development of chronic inflammation. In this review, we focus on the molecular mechanisms by which an altered bile acid signaling promotes intestinal inflammation.
Keywords: FXR; GPBAR1; RORγt; bile acids; intestinal immunity; intestinal microiota.