Sea anemone-derived bioactive peptides alleviate ulcerative colitis via remodeling the gut microbiota-metabolite-immune axis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited therapeutic options. This study investigates the protective effects of bioactive peptides derived from sea anemone (ACPs), prepared by enzymatic hydrolysis, in a dextran sulfate sodium (DSS)-induced murine model of UC. Notably, the peptide ERRK was identified as a dominant component of the ACPs mixture. Remarkably, low-dose ACPs (200 mg/kg) demonstrated superior efficacy over higher doses in ameliorating disease severity, as evidenced by reduced disease activity index (DAI) scores, increased colon length, and improved histopathology. ACPs significantly downregulated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and upregulated anti-inflammatory cytokines (TGF-β, IL-10), while restoring intestinal barrier integrity via increased expression of tight junction proteins (ZO-1, Occludin, Claudin-1). Multi-omics analyses revealed that ACPs remodeled gut microbiota composition, enriched beneficial genera ( Muribaculum , Prevotella ), and modulated host serum metabolites, particularly pathways related to butyrate and tryptophan metabolism. These findings underscore the potential of ACPs, especially at low doses, as a novel functional food for UC management through integrated modulation of the gut microbiota-metabolite-immune axis.