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<p>Ulcerative colitis (UC) is an inflammatory bowel disease that significantly impacts patients’ quality of life. The pathogenesis of UC remains incompletely understood, with oxidative stress and inflammation emerging as novel research targets. This study first isolated Flos Sophorae immaturus exosome-like nanovesicles (FSIEVs), demonstrating high purity, uniform particle size, and excellent biocompatibility and biosafety, with potential for treating UC. In vivo, FSIEVs improve the overall condition of a dextran sodium sulfate-induced murine model of UC, reduce intestinal inflammation and oxidative stress, and repair intestinal barrier integrity. Moreover, FSIEVs exhibit anti-UC effects by modulating the gut microbiota (enhancing <i>Lactobacillus</i> species), promoting tryptophan metabolism, and increasing the production of indole-3-acetic acid (IAA). Findings from antibiotic treatment, fecal microbiota transplantation (FMT), and intestinal organoid models confirmed that IAA is a key metabolite mediating the anti-UC effects of FSIEVs, and all these approaches significantly activated the aryl hydrocarbon receptor (AhR). The role of AhR in the anti-UC effects of FSIEVs was further validated using AhR antagonists. Notably, FSIEVs alleviated UC symptoms involving the enrichment of beneficial anti-UC <i>Lactobacillus</i> species, <i>L. paracasei</i> by mono-colonization. In summary, FSIEVs improve UC by regulating the gut microbiota and tryptophan metabolites, enhancing IAA production, activating AhR, and suppressing NLRP3 inflammasome activation and ROS production.</p> Graphical Abstract <p></p>

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Flos sophorae immaturus exosome-like nanovesicles alleviate ulcerative colitis by attenuating intestinal oxidative stress and inflammation through activating Aryl hydrocarbon receptor via gut microbiota and tryptophan metabolism regulation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月4日

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  • Hao Wu,
  • Mi-mi Pang,
  • Yao-lei Li,
  • Jin-jian Huang,
  • Shi-zhen Geng,
  • Jia-hui Hong,
  • Pan-miao Liu,
  • Jian-jun Yang

摘要

Ulcerative colitis (UC) is an inflammatory bowel disease that significantly impacts patients’ quality of life. The pathogenesis of UC remains incompletely understood, with oxidative stress and inflammation emerging as novel research targets. This study first isolated Flos Sophorae immaturus exosome-like nanovesicles (FSIEVs), demonstrating high purity, uniform particle size, and excellent biocompatibility and biosafety, with potential for treating UC. In vivo, FSIEVs improve the overall condition of a dextran sodium sulfate-induced murine model of UC, reduce intestinal inflammation and oxidative stress, and repair intestinal barrier integrity. Moreover, FSIEVs exhibit anti-UC effects by modulating the gut microbiota (enhancing Lactobacillus species), promoting tryptophan metabolism, and increasing the production of indole-3-acetic acid (IAA). Findings from antibiotic treatment, fecal microbiota transplantation (FMT), and intestinal organoid models confirmed that IAA is a key metabolite mediating the anti-UC effects of FSIEVs, and all these approaches significantly activated the aryl hydrocarbon receptor (AhR). The role of AhR in the anti-UC effects of FSIEVs was further validated using AhR antagonists. Notably, FSIEVs alleviated UC symptoms involving the enrichment of beneficial anti-UC Lactobacillus species, L. paracasei by mono-colonization. In summary, FSIEVs improve UC by regulating the gut microbiota and tryptophan metabolites, enhancing IAA production, activating AhR, and suppressing NLRP3 inflammasome activation and ROS production.

Graphical Abstract