Xifenghuashi formula ameliorates diarrhea predominant-irritable bowel syndrome by modulating the gut microbiota and the bile acid-FXR-FGF axis: A human trial and an animal experiment
- 1Nanjing University of Chinese Medicine, Nanjing, 210023, China
Abstract
Background and aim: Xifenghuashi formula (XFHS), a traditional Chinese medicine, shows promising effects in treating diarrhea-predominant irritable bowel syndrome (IBS-D), but its mechanisms are unclear. This study aims to confirm XFHS's efficacy in IBS-D treatment and its influence on the gut microbiota-bile acid-farnesoid X receptor (FXR)-fibroblast growth factor19/15 (FGF19/15) axis.
Experimental procedure: A randomized, double-blind, placebo-controlled clinical trial was conducted to assess XFHS's effectiveness. In animal experiments, IBS-D rat models were induced by oral gavage of senna along with restraint stress and divided into six groups: the IBS-D group, XFHS group (administered XFHS), antibiotic group (administered antibiotics), A + XFHS group (administered antibiotics and XFHS), FGF401 (a FGFR4 receptor inhibitor) group (administered FGF401), and F + XFHS group (administered FGF401 and XFHS). Human and rat fecal samples, along with rat liver and terminal ileum samples, were analyzed for bile acid concentration, 16S rRNA sequencing, and western blotting.
Results and conclusion: XFHS could enhance the abundance of bile salt hydrolase (BSH)-active bacteria and decrease the abundance of short-chain fatty acids (SCFAs)-producing bacteria in the IBS-D patients to a certain extent, and the same trend was found in the IBS-D rats. XFHS reduced the concentration of total fecal bile acids (including primary, conjugated, and unconjugated bile acids) in IBS-D patients and rats. However, this effect was eliminated by fibroblast growth factor receptor 4 (FGFR4) blockade in IBS-D rats. Furthermore, XFHS increased the protein expression of FXR and FGF15 in the terminal ileum, FGFR4 in the liver, and decreased the expression of cytochrome P450 7A1 (CYP7A1) in the liver. Overall, XFHS alleviated symptoms of IBS-D and restored the homeostasis of the gut microbiota and bile acid metabolism by regulating the gut microbiota-bile acid-FXR-FGF15-FGFR4 axis.
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BibTeX
@article{wang2026xifenghuashi,
title = {{Xifenghuashi formula ameliorates diarrhea predominant-irritable bowel syndrome by modulating the gut microbiota and the bile acid-FXR-FGF axis: A human trial and an animal experiment}},
author = {Wei Wang and Yao-zhou Tian and Xiao-ran Zhang and Zhen-tao An and Cheng-yu Pan and Yan Chen and Pei-juan Wang and Yu-ping Liu and Hui Li},
journal = {Journal of traditional and complementary medicine},
year = {2026},
month = sep,
doi = {10.1016/j.jtcme.2026.09.002},
url = {https://europepmc.org/article/PMC/PMC13729025},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Xifenghuashi formula ameliorates diarrhea predominant-irritable bowel syndrome by modulating the gut microbiota and the bile acid-FXR-FGF axis: A human trial and an animal experiment
AU - Wei Wang
AU - Yao-zhou Tian
AU - Xiao-ran Zhang
AU - Zhen-tao An
AU - Cheng-yu Pan
AU - Yan Chen
AU - Pei-juan Wang
AU - Yu-ping Liu
AU - Hui Li
PY - 2026
DA - 2026/09/04
JO - Journal of traditional and complementary medicine
DO - 10.1016/j.jtcme.2026.09.002
UR - https://europepmc.org/article/PMC/PMC13729025
AB - Background and aim: Xifenghuashi formula (XFHS), a traditional Chinese medicine, shows promising effects in treating diarrhea-predominant irritable bowel syndrome (IBS-D), but its mechanisms are unclear. This study aims to confirm XFHS's efficacy in IBS-D treatment and its influence on the gut microbiota-bile acid-farnesoid X receptor (FXR)-fibroblast growth factor19/15 (FGF19/15) axis. Experimental procedure: A randomized, double-blind, placebo-controlled clinical trial was conducted to assess XFHS's effectiveness. In animal experiments, IBS-D rat models were induced by oral gavage of senna along with restraint stress and divided into six groups: the IBS-D group, XFHS group (administered XFHS), antibiotic group (administered antibiotics), A + XFHS group (administered antibiotics and XFHS), FGF401 (a FGFR4 receptor inhibitor) group (administered FGF401), and F + XFHS group (administered FGF401 and XFHS). Human and rat fecal samples, along with rat liver and terminal ileum samples, were analyzed for bile acid concentration, 16S rRNA sequencing, and western blotting. Results and conclusion: XFHS could enhance the abundance of bile salt hydrolase (BSH)-active bacteria and decrease the abundance of short-chain fatty acids (SCFAs)-producing bacteria in the IBS-D patients to a certain extent, and the same trend was found in the IBS-D rats. XFHS reduced the concentration of total fecal bile acids (including primary, conjugated, and unconjugated bile acids) in IBS-D patients and rats. However, this effect was eliminated by fibroblast growth factor receptor 4 (FGFR4) blockade in IBS-D rats. Furthermore, XFHS increased the protein expression of FXR and FGF15 in the terminal ileum, FGFR4 in the liver, and decreased the expression of cytochrome P450 7A1 (CYP7A1) in the liver. Overall, XFHS alleviated symptoms of IBS-D and restored the homeostasis of the gut microbiota and bile acid metabolism by regulating the gut microbiota-bile acid-FXR-FGF15-FGFR4 axis.
SN - 2225-4110
ER -