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Background <p>Certain microbes inhabiting the gut have been implicated in maintaining gut homeostasis and promoting gut damage repair. Lachnospiraceae members were highly detected in dysbiotic IL-10 KO mice that displayed similar physiological outcomes as control mice. Lachnospiraceae is a highly diverse family of microbes that have been shown to display both commensal and pathogenic characteristics in the colon environment.</p> Results <p>We investigated the impact of genetic variation in five Lachnospiraceae strains on lowering cellular inflammation and reactive oxygen species (ROS) levels. Cell-free spent media (CFSM) from <i>Eubacterium rectale</i> resulted in lowered ROS, and nitric oxide levels in stressed colon cells and colon organoids. CFSM-treated organoids showed reduced ROS accumulation, improved epithelial integrity, and partial recovery of barrier function compared to oxidatively stressed controls. We demonstrated through shotgun metagenomics, metabolomics, host RNA sequencing, and molecular techniques that glutathione (GSH) biosynthesized by <i>E. rectale</i> alleviated host ROS damage. We showed downregulation of cell stress and immune response genes, indicating recovery from ROS stress. Chemical depletion of GSH in CFSM confirmed the role of microbial derived GSH in alleviation of ROS in colon cells.</p> Conclusions <p>In this study, we identify <i>E. rectale</i> as a potential probiotic by lowering colon inflammation and ROS damage through production of reduced glutathione. Microbially derived GSH has not been well established in the Lachnospiraceae family which are a large member of the overall gut microbiota. Understanding more about the impacts of microbial functions including GSH on lowering inflammation is needed to develop potential probiotics or therapies for chronic inflammatory conditions.</p> <p><MediaObject ID="MOESM10"> <VideoObject FileRef="MediaObjects/40168_2026_2457_MOESM10_ESM.mp4" VideoID="BPFHmtzzysdErD4cwTkvpM"> <Caption Language="En" xml:lang="en"> <CaptionContent> <p>Video Abstract</p> </CaptionContent> </Caption> </VideoObject> </MediaObject></p>

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Microbially derived glutathione from Eubacterium rectale alleviates oxidative stress and promotes intestinal epithelial recovery

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年8月4日

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  • Tanner G. Richie,
  • Hallie Wiechman,
  • Brooke Vogt,
  • Carson Ingold,
  • Leah Heeren,
  • Abigail Kamke,
  • Sophia Pogranichniy,
  • Kourtney Monk,
  • Trey Summers,
  • Qinghong Ran,
  • Soumyadev Sarkar,
  • Brandon L. Plattner,
  • Ashley M. Sidebottom,
  • Eugene B. Chang,
  • Sonny T. M. Lee

摘要

Background

Certain microbes inhabiting the gut have been implicated in maintaining gut homeostasis and promoting gut damage repair. Lachnospiraceae members were highly detected in dysbiotic IL-10 KO mice that displayed similar physiological outcomes as control mice. Lachnospiraceae is a highly diverse family of microbes that have been shown to display both commensal and pathogenic characteristics in the colon environment.

Results

We investigated the impact of genetic variation in five Lachnospiraceae strains on lowering cellular inflammation and reactive oxygen species (ROS) levels. Cell-free spent media (CFSM) from Eubacterium rectale resulted in lowered ROS, and nitric oxide levels in stressed colon cells and colon organoids. CFSM-treated organoids showed reduced ROS accumulation, improved epithelial integrity, and partial recovery of barrier function compared to oxidatively stressed controls. We demonstrated through shotgun metagenomics, metabolomics, host RNA sequencing, and molecular techniques that glutathione (GSH) biosynthesized by E. rectale alleviated host ROS damage. We showed downregulation of cell stress and immune response genes, indicating recovery from ROS stress. Chemical depletion of GSH in CFSM confirmed the role of microbial derived GSH in alleviation of ROS in colon cells.

Conclusions

In this study, we identify E. rectale as a potential probiotic by lowering colon inflammation and ROS damage through production of reduced glutathione. Microbially derived GSH has not been well established in the Lachnospiraceae family which are a large member of the overall gut microbiota. Understanding more about the impacts of microbial functions including GSH on lowering inflammation is needed to develop potential probiotics or therapies for chronic inflammatory conditions.

Video Abstract