Analysis of Multi-Site Bile Acid Metabolic Profile Reveals an Association Between Bile Acid–FXR Signaling and Visceral Hypersensitivity in Heterotypic Intermittent Stress-Induced IBS
- 1Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700, China
- 2Acupuncture-Moxibustion and Tuina College, Nanjing University of Chinese Medicine, Nanjing 210023, China
- 3Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China
Abstract
Visceral hypersensitivity (VH) is a hallmark of irritable bowel syndrome (IBS), establishing a reliable VH model is vital for investigating the disorder. While the impact of chronic stress on bile acid (BA) metabolism remains unclear. The exploratory study aimed to evaluate a heterotypic intermittent stress (HIS)-induced rat model of VH and characterize associated alterations in BA metabolism and farnesoid X receptor (FXR) signaling. Rats underwent a 9-day HIS regimen, and VH was assessed by electromyographic recording of the visceromotor response to colorectal distension. BA profiles in feces, colon, and serum were quantified by HPLC-MS/MS, and colonic FXR and CGRP expression were examined by Western blot, immunohistochemistry, and three-dimensional confocal reconstruction. HIS induced significant VH without organic colonic pathology, accompanied by increased CGRP-positive nerve fibers. The bile acid pool composition region-specific alterations in feces, colon, and serum. Specifically, the free-to-conjugated BA ratio was significantly increased in the colon and decreased in the serum of HIS rats, whereas no significant difference was detected in feces, while species-level changes were compartment-specific. Colonic FXR was upregulated and spatially associated with CGRP-positive fibers; in a preventive guggulsterone-treated group, both signals were reduced. These findings indicate that HIS-induced VH is associated with region-specific alterations in BA metabolism and colonic FXR signaling change, identifying the BA–FXR axis as a candidate pathway meriting functional validation as a potential therapeutic target for IBS.
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BibTeX
@article{jiang2026analysis,
title = {{Analysis of Multi-Site Bile Acid Metabolic Profile Reveals an Association Between Bile Acid–FXR Signaling and Visceral Hypersensitivity in Heterotypic Intermittent Stress-Induced IBS}},
author = {Shiyuan Jiang and Chang Gao and Yafang Song and Ninan Zhang and Zhiyun Zhang and Xiaoyu Liu and Yangshuai Su and Xiaoyu Wang and Tao Li},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209293},
url = {https://www.mdpi.com/1422-0067/27/20/9293},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Analysis of Multi-Site Bile Acid Metabolic Profile Reveals an Association Between Bile Acid–FXR Signaling and Visceral Hypersensitivity in Heterotypic Intermittent Stress-Induced IBS
AU - Shiyuan Jiang
AU - Chang Gao
AU - Yafang Song
AU - Ninan Zhang
AU - Zhiyun Zhang
AU - Xiaoyu Liu
AU - Yangshuai Su
AU - Xiaoyu Wang
AU - Tao Li
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209293
UR - https://www.mdpi.com/1422-0067/27/20/9293
AB - Visceral hypersensitivity (VH) is a hallmark of irritable bowel syndrome (IBS), establishing a reliable VH model is vital for investigating the disorder. While the impact of chronic stress on bile acid (BA) metabolism remains unclear. The exploratory study aimed to evaluate a heterotypic intermittent stress (HIS)-induced rat model of VH and characterize associated alterations in BA metabolism and farnesoid X receptor (FXR) signaling. Rats underwent a 9-day HIS regimen, and VH was assessed by electromyographic recording of the visceromotor response to colorectal distension. BA profiles in feces, colon, and serum were quantified by HPLC-MS/MS, and colonic FXR and CGRP expression were examined by Western blot, immunohistochemistry, and three-dimensional confocal reconstruction. HIS induced significant VH without organic colonic pathology, accompanied by increased CGRP-positive nerve fibers. The bile acid pool composition region-specific alterations in feces, colon, and serum. Specifically, the free-to-conjugated BA ratio was significantly increased in the colon and decreased in the serum of HIS rats, whereas no significant difference was detected in feces, while species-level changes were compartment-specific. Colonic FXR was upregulated and spatially associated with CGRP-positive fibers; in a preventive guggulsterone-treated group, both signals were reduced. These findings indicate that HIS-induced VH is associated with region-specific alterations in BA metabolism and colonic FXR signaling change, identifying the BA–FXR axis as a candidate pathway meriting functional validation as a potential therapeutic target for IBS.
SN - 1422-0067
ER -