Bile acids (BAs) are a class of hepatically derived metabolite-hormones with prominent roles in nutrient absorption, metabolic and immune homeostasis in the intestine. BAs are ligands for multiple nuclear receptors (NRs), through which they confer transcriptional regulation on target genes that form an enterohepatic hormonal feedback loop to regulate BA synthesis and maintain lipid homeostasis. Endogenous BAs made by the host undergo significant biotransformation by the gut microbiota in the intestine, which diversifies the intestinal BA pool and facilitate host–microbiota cross-talk through BA-mediated signaling. BAs dysregulation contributes to development of metabolic diseases, pathological inflammation and colon cancer. This review provides a brief historic perspective of the study of NR-mediated BA signaling transduction, with a focus on recent advancements in understanding the active role the gut microbiome plays in reshaping intestinal BA landscape, and the implications of novel microbially derived BAs in modulating immune homeostasis and cancer development in the host. Targeting the BA–NR signaling axis for pharmacological intervention provides ample opportunities in the prevention and treatment of intestinal diseases.
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