Pleiotropic immunoregulation by bile acids in pathophysiology

Bile acids (BAs) have evolved from their classical role in lipid digestion to become central signaling molecules that integrate host metabolism, gut microbiota, and immune function. This review examines how diverse BAs regulate both innate and adaptive immunity through specific receptors—including farnesoid X receptor, Takeda G-protein-coupled receptor 5, vitamin D receptor, and retinoid orphan receptors—modulating the activity of macrophages, dendritic cells, T cells, natural killer cells, and natural killer T cells. Tissue−specific BA signaling influences immune homeostasis in the intestine, liver, central nervous system, and tumor microenvironment. Furthermore, we discuss the pathogenic role of dysregulated BA signaling in inflammatory, autoimmune, metabolic, and malignant diseases, and evaluate emerging therapeutic strategies that target BA pathways via synthetic ligands, engineered microbes, and dietary modulation. Leveraging BA-immune crosstalk to advance research on precision immunotherapy and microbiome-based interventions is a promising area of research.