Bile acid-microbiota interactions in multiple sclerosis: From experimental models to early clinical evidence.

Abstract

This article examines the bidirectional relationship between bile acid metabolism and the intestinal microbiota and explores how disruptions in this interaction may contribute to the pathophysiology of multiple sclerosis. Bile acids are presented not merely as digestive end-products but as bioactive signaling molecules capable of regulating immune responses, maintaining epithelial and neural homeostasis, and influencing neuroinflammatory processes. Experimental work demonstrates that alterations in microbial composition affect bile acid diversity and circulation, while bile acids themselves shape gut microbial ecology through antimicrobial and signaling mechanisms. In preclinical models, specific bile acid species modulate the balance between pro-inflammatory and regulatory immune cells, suppress harmful activation states in astrocytes and microglia, and reduce neuroinflammation. Human studies show consistent disturbances in circulating bile acid profiles in individuals with multiple sclerosis, with some patterns associated with increased disability progression and markers of neurodegeneration. Early clinical interventions also indicate that therapeutic modulation of bile acid pathways is feasible and biologically active, although clinical efficacy remains to be established. Overall, the article highlights bile acid-microbiota interactions as a unifying conceptual framework linking environmental influences, metabolic status, immune dysregulation, and central nervous system injury. By integrating evidence from experimental models and emerging clinical observations, the authors propose that this metabolic and microbial axis may serve both as a source of novel biomarkers and as a target for future disease-modifying therapies.