Role of Bile Acid Receptors in Non-Infectious Diarrhea: A Narrative Review.

Non-infectious diarrhea constitutes a prevalent gastrointestinal pathology that severely compromises patient well-being. Its etiology is progressively associated with gut-liver axis dysfunction, although exact molecular pathways remain undefined. This narrative review consolidates the existing research to investigate 5 distinct bile acid-activated receptors: farnesoid X receptor (FXR), Takeda G protein-coupled receptor 5 (TGR5/GPBAR1), pregnane X receptor (PXR), vitamin D receptor (VDR), and retinoid-related orphan receptor gamma t (RORγt). These molecules function as pivotal hubs linking bile acid metabolism, microbial community structure, and intestinal homeostatic balance. Synthesized hepatically and biotransformed by commensal bacteria, bile acids signal through these receptors; specifically, FXR governs bile acid biosynthesis and epithelial barrier strength, TGR5 modulates motility and inflammatory responses, and PXR and VDR attenuate inflammation via nuclear factor-kappa B (NF-kappaB) suppression, while RORγt regulates immunity through T helper 17 (Th17) cell modulation. Perturbations within this axis-manifesting as defective bile acid reclamation, microbiota dysbiosis, or receptor malfunction-compromise intestinal permeability, provoke electrolyte imbalances, and disrupt immune equilibrium, thereby driving bile acid diarrhea, diarrhea-predominant irritable bowel syndrome, and post-surgical diarrheal conditions. Current data suggest FXR activation is essential for driving bile acid diarrhea management, whereas TGR5 overactivation underlies the hypermotility observed in diarrhea-predominant irritable bowel syndrome. Additionally, rifaximin, acting as a PXR agonist, provides therapeutic benefit. This manuscript evaluates bile acid receptor contributions to non-infectious diarrhea, emphasizing the translational potential of targeting these signaling cascades.