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Background <p>Ulcerative colitis (UC) is a chronic inflammatory disorder marked by epithelial barrier disruption and persistent intestinal inflammation. Despite extensive research, its complex etiology continues to pose therapeutic challenges. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has recently been implicated in UC pathogenesis. Additionally, the gut microbiota and its metabolites play a pivotal role in maintaining intestinal homeostasis and barrier integrity.</p> Purpose <p>This study aimed to investigate the therapeutic potential of a phytotherapeutic agent QCHS to alleviate UC by modulating ferroptosis and the microbiota-metabolome axis, with a particular focus on the role of <i>Lactobacillus gasseri</i> (<i>L. gasseri</i>).</p> Methods <p>A DSS-induced UC mouse model was used to evaluate QCHS efficacy. Gut microbial composition and metabolomic alterations were analyzed via 16S rDNA sequencing and UHPLC-MS/MS. <i>L. gasseri</i> was cultured in vitro to assess the impact of QCHS on its growth. RSL3-induced cell death was modeled in NCM-460 cells and ferroptosis-related changes were examined using transmission electron microscopy, immunohistochemistry, quantitative PCR, and Western blotting.</p> Results <p>QCHS significantly mitigated DSS-induced ferroptosis in colonic tissues, with <i>L. gasseri</i> identified as a key mediator. Notably, <i>L. gasseri</i> was found to act as a novel ferroptosis inhibitor. In vitro studies confirmed that <i>L. gasseri</i> suppressed RSL3-induced ferroptosis in NCM-460 cells via activation of the GSH/GPX4 pathway.</p> Conclusion <p>This study provides compelling evidence for the regulatory role of QCHS on the microbiota-metabolome axis and ferroptosis in UC. It also uncovers a novel function of <i>L. gasseri</i> as a ferroptosis inhibitor, offering promising insights into microbiota-targeted and ferroptosis-modulating therapeutic strategies for UC.</p> Graphical Abstract <p></p>

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Qing-Chang-Hua-Shi granule ameliorates experimental colitis by modulating Lactobacillus gasseri-mediated ferroptosis metabolic pathway

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月26日

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  • Cheng Cheng,
  • Lei Zhu,
  • Jingyi Hu,
  • Wan Feng,
  • Weiyang Li,
  • Ryan Au,
  • Yanan Li,
  • Feng Xu,
  • Yuguang Wu,
  • Yuan Cui,
  • Zhe Di,
  • Bin Li,
  • Yongchang Miao,
  • Yao Lin,
  • Lilin Ge,
  • Hong Shen

摘要

Background

Ulcerative colitis (UC) is a chronic inflammatory disorder marked by epithelial barrier disruption and persistent intestinal inflammation. Despite extensive research, its complex etiology continues to pose therapeutic challenges. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has recently been implicated in UC pathogenesis. Additionally, the gut microbiota and its metabolites play a pivotal role in maintaining intestinal homeostasis and barrier integrity.

Purpose

This study aimed to investigate the therapeutic potential of a phytotherapeutic agent QCHS to alleviate UC by modulating ferroptosis and the microbiota-metabolome axis, with a particular focus on the role of Lactobacillus gasseri (L. gasseri).

Methods

A DSS-induced UC mouse model was used to evaluate QCHS efficacy. Gut microbial composition and metabolomic alterations were analyzed via 16S rDNA sequencing and UHPLC-MS/MS. L. gasseri was cultured in vitro to assess the impact of QCHS on its growth. RSL3-induced cell death was modeled in NCM-460 cells and ferroptosis-related changes were examined using transmission electron microscopy, immunohistochemistry, quantitative PCR, and Western blotting.

Results

QCHS significantly mitigated DSS-induced ferroptosis in colonic tissues, with L. gasseri identified as a key mediator. Notably, L. gasseri was found to act as a novel ferroptosis inhibitor. In vitro studies confirmed that L. gasseri suppressed RSL3-induced ferroptosis in NCM-460 cells via activation of the GSH/GPX4 pathway.

Conclusion

This study provides compelling evidence for the regulatory role of QCHS on the microbiota-metabolome axis and ferroptosis in UC. It also uncovers a novel function of L. gasseri as a ferroptosis inhibitor, offering promising insights into microbiota-targeted and ferroptosis-modulating therapeutic strategies for UC.

Graphical Abstract