Tetrastigma hemsleyanum polysaccharides alleviate inflammatory bowel disease via the gut microbiota-SCFA-GPR43 signaling axis

  • Phytomedicine. 2025 Dec:149:157523. doi: 10.1016/j.phymed.2025.157523.
Yishan Lv  1 ,  Liu Yang  1 ,  Wenxuan Li  1 ,  Yiwen Hu  1 ,  Bingqi Zhu  1 ,  Mingyuan Zhou  1 ,  Yujian Ye  2 ,  Zhishan Ding  3 ,  Fangmei Zhou  4
Affiliations
  • 1. School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China.
  • 2. Department of Dermatology, Third People's Hospital of Hangzhou, Hangzhou, China.
  • 3. School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China. Electronic address: [email protected].
  • 4. School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China. Electronic address: [email protected].
PMID: 41308392 DOI: 10.1016/j.phymed.2025.157523
Abstract

Introduction: This study investigates the protective mechanism of Tetrastigma hemsleyanum Polysaccharides (THP) against inflammatory bowel disease (IBD) by focusing on its interactions with gut microbiota and metabolites.

Objectives: The study aims to elucidate how THP exerts anti-inflammatory effects on IBD through modulating gut microbiota and activating relevant signaling pathways.

Methods: A dextran sulfate sodium (DSS)-induced IBD mouse model was used. Antibiotic-treated mice showed that THP's protective effect is microbiota-dependent. Fecal microbiota transplantation (FMT) from THP-treated donors replicated the therapeutic benefits in recipient mice. In vivo studies with GPR43 agonists/inhibitors and in vitro experiments in GPR43-knockdown HT-29 cells explored the signaling pathways. A Caco-2/HT-29 co-culture model assessed the direct protection of intestinal epithelial cells by THP-derived metabolites. 16S rRNA Sequencing and metabolomics analyzed microbiota and metabolic changes.

Results: THP's protective effect was abolished in microbiota-depleted mice. FMT confirmed the microbiota-mediated effect. THP suppressed intestinal inflammation via the GPR43/β-arrestin2-JNK pathway. THP-derived metabolites directly protected intestinal epithelial cells. THP modulated gut microbiota, increased short-chain fatty acid (SCFA) production, and stimulated Resolvin E1 biosynthesis, which were associated with inflammation resolution and epithelial repair.

Conclusion: THP exerts anti-colitic effects by modulating gut microbiota, activating GPR43-mediated signaling, and enhancing pro-resolving lipid mediators, showing potential for IBD treatment.

Keywords
Gut microbiota; Intestinal mucosal barrier; Short-chain fatty acids; Tetrastigma hemsleyanum polysaccharides.
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