Anti-Inflammatory Effect of Clostridium Butyricum-Derived Extracellular Vesicles in Ulcerative Colitis: Impact on Host microRNAs Expressions and Gut Microbiome Profiles

Score Probiotics extracellular vesicles (EVs) have shown potential as EV-based nanomaterials therapy for the treatment of inflammatory bowel disease (IBD). Although probiotic Clostridium butyricum has been reported to be protective in various models of intestinal inflammation, the therapeutic effects of Clostridium butyricum -derived extracellular vesicles (CbEVs) in IBD remain to be demonstrated. Methods and Results In this study, we combined multi-omics sequencing with an in vitro model of lipopolysaccharide-induced RAW264.7 cells and an in vivo mouse model of dextran sodium sulfate-induced colitis to explore the regulatory impact and mechanism of CbEVs in ulcerative colitis. Through small RNA sequencing, we found that microRNA is involved in the alleviation of colonic inflammation under CbEVs treatment. Mechanistically, CbEVs restored miR-199a-3p expression, interacting with map3k4, and thereby suppressed proinflammatory MAPK and NF-κB signaling. Additionally, metagenomic sequencing demonstrated that CbEVs alleviated bacterial dysbiosis in colitis mice and significantly reduced the abundance of the bacterial pathogens Escherichia coli and Shigella flexneri . Furthermore, CbEVs regulated the microbial tryptophan metabolites, which further improved intestinal barrier integrity and inhibited the inflammatory response in colitis mice. Conclusion Clostridium butyricum -derived extracellular vesicles could be a novel agent for the treatment of colitis and miR-199a-3p could be a potential target for IBD treatment. This article is protected by copyright. All rights reserved