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

• Published in: Molecular nutrition & food research 2023-07, Vol.67 (13), p.e2200884-n/a
• Main Authors: Ma, Lingyan, Lyu, Wentao, Song, Yuanyuan, Chen, Kai, Lv, Lu, Yang, Hua, Wang, Wen, Xiao, Yingping
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Anti-Inflammatory Agents; Bacteria; Clostridium butyricum; Clostridium butyricum - genetics; colitis; Colitis - drug therapy; Colitis, Ulcerative - chemically induced; Colitis, Ulcerative - drug therapy; Colon; Dextran; Dextran Sulfate - toxicity; Dextrans; Disease Models, Animal; Dysbacteriosis; E coli; Extracellular Vesicles; Gastrointestinal Microbiome; Gene sequencing; gut microbiota; Inflammation - drug therapy; Inflammatory bowel disease; Inflammatory Bowel Diseases; Inflammatory response; Intestinal microflora; Intestine; Lipopolysaccharides; MAP kinase; Metabolites; Metagenomics; Mice; Microbiomes; Microorganisms; microRNA; MicroRNAs; MicroRNAs - genetics; miRNA; Nanomaterials; Nanotechnology; Probiotics; Ribonucleic acid; RNA; Sodium sulfate; Tryptophan; Ulcerative colitis; Vesicles
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.202200884

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 C. butyricum‐derived extracellular vesicles (CbEVs) in IBD remain to be demonstrated. Methods and 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. 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. This study highlights that probiotic‐derived extracellular vesicles may be a novel agent for treating colitis and proposes that miR‐199a‐3p is a potential target for inflammatory bowel disease treatment.