Abstract
The protective effects of the milk fat globule membrane (MFGM) in alleviating inflammation have been reported. However, limited attention has been paid to the key fraction of milk fat globule membrane protein (MFGMP). This study investigated the protective effects of camel MFGMP against dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. The results revealed that administering 50 mg/kg MFGMP significantly alleviated colonic inflammation, as evidenced by a marked decrease in IL-6, IL-1β, and TNF-α levels, along with pathological damage in DSS-induced mice with UC. MFGMP supplementation partially regulated gut microbiota dysbiosis in mice with UC by increasing α-diversity and the relative abundance of beneficial gut bacteria, such as Lactobacillus, while decreasing the abundance of Akkermansia. Additionally, MFGMP treatment exhibited significant regulatory effects on metabolites, particularly amino acid metabolism, in the feces. Specifically, this treatment restored L-valine to normal physiological levels and increased the concentrations of L-leucine, L-lysine, and L-tyrosine to nearly twice their baseline levels, whereas the concentration of L-tryptophan increased threefold. These upregulated amino acids were negatively correlated with pro-inflammatory cytokines and positively correlated with the anti-inflammatory cytokine IL-10, as indicated by Spearman's correlation analysis. Furthermore, the significant reduction in the mRNA expression levels of WNT-1, β-catenin, and Cyclin D1 suggests that MFGMP exerts a positive effect on UC via the Wnt/β-catenin pathway. These findings indicate that MFGMP exerts a protective effect against UC by modulating intestinal microbiota and amino acid metabolism in mice, with potential implications for treating intestinal inflammatory diseases.