Bile acid modulation of host immunity

Bile acids are cholesterol-derived molecules primarily recognized for their roles in digestion and lipid metabolism. However, decades of research have consistently highlighted their broader and diverse biological significance, particularly their modulation of host immunity. This review investigates the molecular mechanisms through which bile acids regulate immune responses, including their effects on macrophages, dendritic cells, and T cells. Bile acids engage with nuclear and membrane receptors, notably the farnesoid X receptor and the Takeda G-protein-coupled receptor 5, to influence immune cell differentiation, communication, and signaling. These regulations could shape disease outcomes, such as in inflammatory bowel diseases, intestinal and liver diseases, and liver and colorectal cancers. Additionally, we highlight recent advances in photoaffinity labeling and chemical proteomics that have broadened our understanding of bile acid-induced signaling by identifying novel bile acid-targeting proteins. By elucidating the mechanisms of action and significance of bile acid regulation, we provide insights into how bile acids serve as critical mediators between metabolism and immunity-opening new avenues for therapeutic interventions targeting bile acid signaling pathways.