Gut commensal Lachnospira eligens alleviates ulcerative colitis by mediating isodeoxycholic acid via the STAT3/NF-κB signaling pathway

<title>Abstract</title> <p> Ulcerative colitis (UC) is linked to an imbalance in gut microbiota and changes in microbial metabolism. Nevertheless, the mechanisms by which particular commensal bacteria and their metabolites mitigate colitis remain elusive. Here we explored the therapeutic efficacy of different <italic>Lachnospira eligens</italic> strains and its gut-derived metabolite isodeoxycholic acid (isoDCA) in dextran sulfate sodium (DSS)-induced colitis mice. Administration of live <italic>L. eligens</italic> significantly reduced the severity of colitis by enhancing intestinal barrier integrity and decreasing colonic inflammation. Furthermore, live <italic>L. eligens</italic> DSM3376 modified the intestinal metabolic profile and notably influenced bile acid metabolism, with untargeted metabolomics pinpointing isoDCA as a key metabolite linked to the improvement of the disease. The treatment of isoDCA replicated the protective effects in DSS-treated mice, alleviating mucosal damage, suppressing pro-inflammatory signaling and inhibiting the activation of the STAT3 and NF-κB pathways. Our findings reveal a protective <italic>L. eligens</italic> –isoDCA axis against colitis and indicate that functionally characterized gut bacteria or bile acid-derived metabolites may serve as promising therapeutic approaches for UC. </p>