Recombinant antimicrobial peptide microcin J25 alleviates DSS-induced colitis via regulating intestinal barrier function and modifying gut microbiota

•Recombinant antimicrobial peptide Microcin J25 can attenuate inflammation and improve disrupted barrier function.•Microcin J25 may improve the intestinal flora disorder in mice with colitis.•Targets of MccJ25 may be genus Lactobacillus, Bacteroides and Akkermansia.•Bloom of Lactobacillus, combined with the reduction of Akkermansia and Bacteroides were closely related to the recovery of gut inflammation. Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is rising constantly all over the world. However, current medical treatments are not universally practical. Microcin J25 (MccJ25), a member of the lasso peptides class, has excellent antimicrobial activity both in vitro and in vivo. Here, we assessed the anti-inflammatory effects of MccJ25 through DSS-induced UC mouse model. MccJ25 significantly ameliorated the UC-associated parameters such as decreased body weight, increased disease activity index (DAI) and shortened colon length. MccJ25 also provides barrier protection by preserving structural integrity and reducing inflammatory infiltrates of colon epithelium. The underlying mechanism may be associated with gut microbiota. To test this uncertainty, co-housing experiment was performed, and results indicate homogenized microbiota could relief the inflammatory. Meanwhile, we also proved the prominent role of the possible targets of MccJ25, namely genus Lactobacillus, Bacteroides and Akkermansia (as well as the possible strains related to the important OTUs) in inflammation status through comprehensive analysis. In conclusion, MccJ25 effectively attenuates inflammation and improves disrupted barrier function, and the MccJ25-modified gut microbiota plays a central role in this process.