Novel Role of Gut‐Derived Roseburia Intestinalis in Safeguarding Intestinal Barrier Integrity and Microenvironment Homeostasis During Arsenic Exposure

Arsenic exposure disrupts intestinal barriers and gut microenvironment. Fecal microbiota transplantation (FMT) alleviates arsenic‐induced damage, with gut‐derived Roseburia intestinalis (R.i) identified as a key protective strain. R.i administration counters arsenic toxicity through immunomodulatory pathways and metabolites. Supplementation with R.i presents a novel therapeutic strategy against arsenic‐related intestinal disorders. Abstract As a well‐known metalloid, arsenic usually causes human intestinal disorders via contaminated drinking water. However, the mechanisms underlying how arsenic induces intestinal injury remain unresolved, and the effective means of intervention are very limited. By establishing an acute arsenic exposure animal model, this work shows that arsenic disrupts the mechanical, chemical, immunological, and biological barriers of the intestine, and thereby changes the microenvironment in the gut. We further verify that the administration of fecal microbiota transplantation with a healthy gut microbiome alleviates the intestinal damage induced by arsenic. Intriguingly, by using 16S rRNA sequencing and anaerobic culture, we identify a novel role of gut‐derived strain, Roseburia intestinalis, which exhibits significant protection against arsenic‐induced intestinal toxicity in mice. By applying non‐targeted metabolomics after arsenic exposure, this work further establishes the beneficial effects and the potential metabolites associated with Roseburia intestinalis, including cacodylic acid, carindone, 3‐hydroxymelatonin and L‐galacto‐2‐heptulose, etc. Transcriptomic analysis reveals that the protective effects of Roseburia intestinalis against arsenic‐induced intestinal injury include mainly immune‐related pathways. Taken together, these findings highlight that supplementation with gut‐derived Roseburia intestinalis is an alternative strategy that could be used in the prevention and treatment of arsenic‐related intestinal disorders. Arsenic exposure disrupts intestinal barriers and gut microenvironment. Fecal microbiota transplantation (FMT) alleviates arsenic-induced damage, with gut-derived Roseburia intestinalis (R.i) identified as a key protective strain. R.i administration counters arsenic toxicity through immunomodulatory pathways and metabolites. Supplementation with R.i presents a novel therapeutic strategy against arsenic-related intestinal disorders. Abstract As a well-known metalloid, arsenic usually causes human intestinal disorders via contaminated drinking water. However, the mechanisms underlying how arsenic induces intestinal injury remain unresolved, and the effective means of intervention are very limited. By establishing an acute arsenic exposure animal model, this work shows that arsenic disrupts the mechanical, chemical, immunological, and biological barriers of the intestine, and thereby changes the microenvironment in the gut. We further verify that the administration of fecal microbiota transplantation with a healthy gut microbiome alleviates the intestinal damage induced by arsenic. Intriguingly, by using 16S rRNA sequencing and anaerobic culture, we identify a novel role of gut-derived strain, Roseburia intestinalis, which exhibits significant protection against arsenic-induced intestinal toxicity in mice. By applying non-targeted metabolomics after arsenic exposure, this work further establishes the beneficial effects and the potential metabolites associated with Roseburia intestinalis, including cacodylic acid, carindone, 3-hydroxymelatonin and L -galacto-2-heptulose, etc. Transcriptomic analysis reveals that the protective effects of Roseburia intestinalis against arsenic-induced intestinal injury include mainly immune-related pathways. Taken together, these findings highlight that supplementation with gut-derived Roseburia intestinalis is an alternative strategy that could be used in the prevention and treatment of arsenic-related intestinal disorders. Advanced Science, Volume 12, Issue 42, November 13, 2025.