Cod Skin Collagen Peptides Alleviate Ulcerative Colitis by Regulating Gut Microbiota to Inhibit NLRP3 Inflammasome Activation

ABSTRACT

Enteral nutrition is an important intervention for ulcerative colitis, and collagen can improve immune responses and repair the intestinal barrier. Low‐molecular‐weight peptides from cod skin have demonstrated anti‐inflammatory and mucosal protective effects; however, the mechanism by which they alleviate colitis through gut microbiota modulation remains unclear. This study examined the mechanism by which cod skin collagen oligopeptide powder (CP) affects the gut flora to treat ulcerative colitis (UC). This study evaluated CP in mice with dextran sodium sulfate (DSS)‐induced UC and used 16S rRNA sequencing to analyze its effect on the gut flora. Fecal microbiota transplantation (FMT) demonstrated the role of CP in modulating gut microbiota in the treatment of UC. Hematoxylin and eosin staining, immunohistochemistry, histology, and enzyme‐linked immunosorbent assay (ELISA) assessed CP's effects on colon structure and inflammation. 16S rRNA sequencing showed that CP therapy significantly altered the diversity and organization of the intestinal microbiota in UC mice. FMT demonstrated that CP alleviates UC by modifying the gut microbiota, providing insights into the underlying mechanisms. CP treatment significantly improved body weight, colon length, and histopathological scores in DSS‐induced colitis mice, reduced the levels of NLRP3, Caspase‐1, ASC, IL‐1β, and IL‐18, promoted colonic healing, and alleviated tissue damage. CP inhibited fibrosis by upregulating ZO‐1 and Occludin while downregulating α‐SMA, Vimentin, Snail, and Slug. In conclusion, CP may treat colitis in mice by suppressing NLRP3 inflammasome activation via regulation of the gut microbiota.