The gut microbiome–bile acid-FXR interplay: a pivotal axis in metabolic and gastrointestinal diseases

The gut microbiota is increasingly recognized as an essential metabolic "organ", involved not only in nutrient extraction and energy metabolism but also in generating diverse bioactive metabolites. Among these metabolites, bile acids (BAs) - initially synthesized in the liver - are substantially modified by bacterial enzymes in the gut, enabling them to engage various host signaling pathways. Notably, these BAs interact with critical host receptors, such as nuclear farnesoid X receptor (FXR) and G protein-coupled BA receptor 1 (TGR5), influencing numerous metabolic processes. Given the complexity and significance of BAs signaling between microbiota-host interactions, a comprehensive review of this interplay is essential. Here, we systematically explore the molecular mechanisms underlying the BA-microbiota axis, emphasizing its role in metabolic, gastrointestinal, and immune-related diseases, with a focus on the roles of FXR signaling pathways.