Role of Bile Acid Receptors in Non-Infectious Diarrhea: A Narrative Review.
4 affiliations
- 1Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
- 2Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
- 3Department of Radiation Oncology, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan, Shandong, China.
- 4The Clinical Medical College, Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan, Shandong, China.
Abstract
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.
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BibTeX
@article{pan2026role,
title = {{Role of Bile Acid Receptors in Non-Infectious Diarrhea: A Narrative Review.}},
author = {Liying Pan and Pancen Ran and Fengxian Jiang and Yahui Wang and Weihao Wang and Rui Zhao and Huaiqian Mu and Guobin Fu},
journal = {Medical science monitor : international medical journal of experimental and clinical research},
year = {2026},
month = oct,
doi = {10.12659/msm.952723},
url = {https://europepmc.org/article/MED/42850871},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Role of Bile Acid Receptors in Non-Infectious Diarrhea: A Narrative Review.
AU - Liying Pan
AU - Pancen Ran
AU - Fengxian Jiang
AU - Yahui Wang
AU - Weihao Wang
AU - Rui Zhao
AU - Huaiqian Mu
AU - Guobin Fu
PY - 2026
DA - 2026/10/09
JO - Medical science monitor : international medical journal of experimental and clinical research
DO - 10.12659/msm.952723
UR - https://europepmc.org/article/MED/42850871
AB - 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.
SN - 1234-1010
SN - 1643-3750
ER -