Hydatid Cyst Fluid of Echinococcus granulosus Alleviates Experimental Ulcerative Colitis by Suppressing Inflammation and Oxidative Stress and Regulating the Gut Microbiota

Ulcerative colitis (UC) is a chronic recurrent inflammatory disease of the colonic mucosa, with a rising global incidence. Hydatid cyst fluid of Echinococcus granulosus (EgHCF) has been shown to alleviate UC inflammation, but how it exerts this protective effect is not yet fully understood. In this study, we investigated the protective efficacy of EgHCF using a dextran sulfate sodium (DSS)-induced acute colitis model in mice and an NCM460 intestinal epithelial cell line. In vivo, EgHCF treatment significantly ameliorated the clinical signs of DSS-induced colitis, counteracted colon shortening and weight loss, and mitigated colonic histopathological damage; furthermore, it enhanced intestinal barrier integrity, suppressed inflammatory responses, reduced oxidative stress, and activated the Keap1/Nrf2 signaling pathway. Gut microbiota analysis revealed that EgHCF attenuated gut microbial dysbiosis by increasing α-diversity and the abundance of Firmicutes and Verrucomicrobiota. Metabolomics analysis further indicated that the tryptophan metabolic pathway plays a prominent role in the treatment of DSS-induced UC mice with EgHCF. In vitro, EgHCF protected the epithelial barrier function of NCM460 cells, significantly inhibited the expression of pro-inflammatory factors iNOS and COX-2, attenuated intracellular ROS levels, and activated the Keap1/Nrf2 pathway in DSS-stimulated NCM460 cells. These findings suggest that EgHCF alleviates DSS-induced colitis by mitigating inflammation and oxidative stress, as well as regulating the gut microbiota, providing novel insights into its role in repairing the intestinal barrier.