Bile acid dysregulation in sepsis: mechanisms, clinical implications, and future perspectives

Sepsis is a life-threatening syndrome caused by a dysregulated host response to infection and remains a major global health challenge because of its high morbidity, mortality, and limited targeted therapeutic options. Accumulating evidence suggests that bile acids (BAs), endogenous metabolites synthesized in the liver and modified by the gut microbiota, are involved in inflammation, barrier integrity, and metabolic homeostasis. Sepsis is associated with alterations in multiple aspects of BA homeostasis, including hepatic synthesis, transporter activity, microbial biotransformation, and enterohepatic circulation. These alterations may influence hepatic function, gut barrier integrity, and immune responses, although their precise role in sepsis progression remains incompletely understood. This review summarizes current advances in BA biology relevant to sepsis, discusses the interactions between BA dysregulation and the liver-gut-microbiota-immune axis, and evaluates the potential and current limitations of BA-related biomarkers and therapeutic strategies. Particular emphasis is placed on unresolved issues, including disease heterogeneity, causality, and clinical translation. By synthesizing current evidence and knowledge gaps, this review provides an updated perspective on BA dysregulation within the broader immunometabolic landscape of sepsis and highlights priorities for future research.