2. Academic Validation
  3. Taurodeoxycholic acid alleviates intestinal inflammation by modulating gut microbiota and TGR5-NF-kappaB axis in DSS-induced colitis

Taurodeoxycholic acid alleviates intestinal inflammation by modulating gut microbiota and TGR5-NF-kappaB axis in DSS-induced colitis

  • Int Immunopharmacol. 2026 Feb 1:170:116056. doi: 10.1016/j.intimp.2025.116056.
Jiahui Gao 1,  Lixiang Li 1,  Shanshan Zhang 1,  Hongyu Zhao 1,  Bingcheng Feng 1,  Chang Liu 1,  Xia Wang 1,  Shiyang Li 2,  Yanqing Li 3,  Dong Zhao 4
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, China; Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, China; Shandong Provincial Clinical Research Center for digestive disease, Qilu Hospital, Shandong University, Jinan 250012, China.
  • 2 Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, China; Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, China; Shandong Provincial Clinical Research Center for digestive disease, Qilu Hospital, Shandong University, Jinan 250012, China; Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
  • 3 Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, China; Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, China; Shandong Provincial Clinical Research Center for digestive disease, Qilu Hospital, Shandong University, Jinan 250012, China; Robot Engineering Laboratory for Precise Diagnosis and Therapy of Gastrointestinal Tumor, Qilu Hospital of Shandong University, Jinan 250012, China. Electronic address: [email protected].
  • 4 Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, China; Medical Integration and Practice Center, Shandong University, Jinan 250012, China; Cholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing 400038, China. Electronic address: [email protected].
PMID: 41448004 DOI: 10.1016/j.intimp.2025.116056
Abstract

Taurodeoxycholic acid (TDCA), a metabolite of Cholesterol, has been shown to be able to regulate various inflammatory responses and improve intestinal inflammation. However, its potential to alleviate colitis through modulating the gut microbiota-bile acid axis remains unclear. Mice were simultaneously administered dextran sulfate sodium (DSS) and TDCA via drinking water to estimate the effect of TDCA on colitis. TDCA-treated mice showed markedly relieved DSS-induced colitis. 16S rDNA Sequencing revealed TDCA selectively remodeled the gut microbiota, notably decreasing the abundances of Desulfovibrionaceae_unclassified, Escherichia-Shigella and increasing Akkermansia. Furthermore, the reshaping of the microbial community was functionally characterized by a marked alteration in the gut bile acid profile, specifically a significant increase in secondary bile acids. Fecal microbiota transplantation (FMT) confirmed the protective role of the TDCA-shaped microbiota, which also transferred the reduction of Desulfovibrionaceae_unclassified and the characteristic bile acid profile to recipient mice. Similarly, transplanting feces after TDCA intervention into recipient mice still increased secondary bile acid levels in the gut to a certain extent. Spearman's correlation analysis further solidified the negative correlation between Desulfovibrionaceae_unclassified and secondary bile acids. Mechanistically, the altered bile acid profiles restored the activation of the bile acid receptor TGR5, but not FXR, thereby inhibiting the NF-κB signaling pathway. The essential role of TGR5 was substantiated as its inhibitor, SBI-115, largely abolished the protective effects of TDCA. In conclusion, our findings demonstrate that TDCA alleviates colitis by orchestrating a microbiota-bile acid-TGR5 signaling cascade, positioning it as a promising therapeutic candidate for inflammatory bowel disease.

Keywords

Bile acid profile; Gut microbiota; TGR5; Taurodeoxycholic acid; Ulcerative colitis.

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