Ligilactobacillus murinus Confers a Dual Benefit: Counteracting Crotonis Fructus-induced Intestinal Toxicity and Synergizing with Its Processed Form against Ulcerative Colitis

Ethnopharmacological relevance Ulcerative colitis (UC) poses a major clinical challenge. Classical Chinese medical texts record the use of Crotonis Fructus (CF), the seeds of Croton tiglium L. , for treating conditions like “chronic dysentery” presenting symptoms similar to UC. However, the clinical application of both raw and processed CF is limited due to intestinal toxicity. Aim of the study This study investigates the role of gut microbiota in mitigating the intestinal toxicity induced by CF and in enhancing the anti-UC efficacy of its processed form. Methods Metagenomic analysis investigated CF-induced intestinal toxicity. The benefits of probiotics combined with CF or processed CF cream were evaluated in Caenorhabditis elegans ( C. elegans ) and a dextran sulfate sodium (DSS)-induced mouse model. Their combined effect was further assessed in DSS-exposed C. elegans , with qRT-PCR measuring intestinal barrier integrity. Results Metagenomic analysis revealed that CF-induced intestinal toxicity was associated with gut microbiota dysbiosis characterized by a pronounced reduction in Ligilactobacillus murinus ( L. murinus) . Supplementation with L. murinus alleviated CF-induced damage in C. elegans . In DSS-induced UC mice, both L. murinus and processed CF cream ameliorated colitis and suppressed TNF-α, IL-6, and IL-1β. When co-administered in DSS-exposed C. elegans , two agents acted synergistically, leading to greater restoration of intestinal barrier integrity and more pronounced upregulation of barrier-function genes. Conclusion This study demonstrates that L. murinus plays a dual role: it mitigates CF-induced intestinal toxicity and acts synergistically with processed CF cream to enhance UC treatment, providing a microbiome-based strategy for safer clinical application.