Conclusion
C. butyricum-derived extracellular vesicles can be a novel agent for the treatment of colitis and miR-199a-3p can be a potential target for IBD treatment.
Results
In this study, multi-omics sequencing is combined 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, the study finds that microRNA is involved in the alleviation of colonic inflammation under CbEVs treatment. Mechanistically, CbEVs restore miR-199a-3p expression, interacting with map3k4, and thereby suppress proinflammatory MAPK and NF-κB signaling. Additionally, metagenomic sequencing demonstrate that CbEVs alleviate bacterial dysbiosis in colitis mice and significantly reduces the abundance of the bacterial pathogens Escherichia coli and Shigella flexneri. Furthermore, CbEVs regulate the microbial tryptophan metabolites, which further improve intestinal barrier integrity and inhibit the inflammatory response in colitis mice.