From natural milk sources to intestinal protection: The role and mechanism of donkey whey protein in alleviating DSS induced colitis in mice

To investigate the effects of donkey whey protein (DWP) on ulcerative colitis and to explore its potential mechanisms, we examined the disease activity index, colonic pathological damage, inflammatory cytokine levels, oxidative stress status, and the gut microbiota composition in DSS-induced colitic mice administered with DWP. Fifty male BALB/c mice divided into five groups: normal control (no DSS), model control (3% DSS), and three DWP doses (0.5, 1.0, 2.0 g/kg) with 3% DSS, designated W1–W3. Feed intake and body weight recorded daily for 28 days. Post-experiment, we measured colonic damage, cytokines, antioxidants, and gut microbiota. The results showed that mice in the W3 group exhibited a significant recovery of body weight (22.96 ± 0.53 g, P < 0.01), with tightly and regularly arranged colonic crypts, abundant goblet cells, and an overall restoration to a near-healthy state. Compared with the C group, the pro-inflammatory cytokine IL-6 was significantly decreased, the anti-inflammatory cytokine IL-10 and inflammatory marker MPO ( P < 0.01) were significantly reduced in all DWP intervention groups. Moreover, all doses of DWP significantly increased the GSH and GSH-Px activity in colitic mice ( P < 0.01). As for gut microbiota analysis, W3 elevated the abundances of Odoribacter, Anaerotruncus and Ligilactobacillus, with some genera approaching the levels observed in the NC group. Results indicate that DWP ameliorated DSS-induced colitis by maintaining intestinal mucosal barrier, enhancing immune responses and antioxidant capacity, and reducing inflammation. Evidence from this study supports utilization of DWP as a natural functional ingredient for adjunctive prevention and treatment of ulcerative colitis.