Immunomodulatory mechanisms of bile acids in autoimmune diseases along the gut-liver axis.

Bile acids (BAs) have evolved from simple digestive surfactants into central signaling molecules that integrate gut microbiota metabolism with host immunity. In autoimmune diseases (AIDs), alterations in the BA pool, driven by changes in microbial transformation capacity and tissue-specific receptor responsiveness, disrupt the homeostasis of the gut-liver-immune axis. These alterations participate in disease onset, progression, and chronicity by weakening epithelial barrier integrity, regulating inflammasome activity, and skewing the Th17/Treg balance, among other mechanisms. This review synthesizes current knowledge on BA synthesis, enterohepatic circulation, and microbial modification. We examine the immune-regulatory network of BAs, which includes both receptor-dependent pathways and receptor-independent mechanisms, and discuss their dysregulation in common AIDs. Finally, we assess emerging therapeutic strategies, including receptor-targeted modulators, microbiome-directed interventions, and combination regimens aimed at restoring metabolic-immune homeostasis. A mechanistic understanding of this network may help improve early diagnosis, patient stratification, and personalized immunotherapy of AIDs.