Roseburia intestinalis‐derived extracellular vesicles ameliorate colitis by modulating intestinal barrier, microbiome, and inflammatory responses

Abstract Inflammatory bowel disease (IBD) is a chronic disorder characterized by recurrent gastrointestinal inflammation, lacking a precise aetiology and definitive cure. The gut microbiome is vital in preventing and treating IBD due to its various physiological functions. In the interplay between the gut microbiome and human health, extracellular vesicles secreted by gut bacteria (BEVs) are key mediators. Herein, we explore the role of Roseburia intestinalis ( R )‐derived EVs (R‐EVs) as potent anti‐inflammatory mediators in treating dextran sulfate sodium‐induced colitis. R was selected as an optimal BEV producer for IBD treatment through ANCOM analysis. R‐EVs with a 76 nm diameter were isolated from R using a tangential flow filtration system. Orally administered R‐EVs effectively accumulated in inflamed colonic tissues and increased the abundance of Bifidobacterium on microbial changes, inhibiting colonic inflammation and prompting intestinal recovery. Due to the presence of Ile‐Pro‐Ile in the vesicular structure, R‐EVs reduced the DPP4 activity in inflamed colonic tissue and increased the active GLP‐1, thereby downregulating the NFκB and STAT3 via the PI3K pathway. Our results shed light on the impact of BEVs on intestinal recovery and gut microbiome alteration in treating IBD.