Lactobacillus plantarum 69-2 combined with α-lactalbumin hydrolysate alleviates DSS-induced ulcerative colitis through the TLR4/NF-κB inflammatory pathway and the gut microbiota in mice

69-2 (L69-2) on a colitis mouse model. The results showed that α-LA hydrolysate with a molecular weight <3 kDa obtained with neutral protease had excellent antioxidant activity and potential to enhance probiotic proliferation. Furthermore, the synergistic application of α-LA hydrolysate and L69-2 could alleviate the adverse impact of colon inflammation by reducing oxidative stress and regulating immune disorders. It maintains the intestinal epithelial barrier, thereby reducing immune system over-activation, promoting the colonization of beneficial bacteria, and regulating intestinal immune responses. Simultaneously, it remodels the structure of the disrupted intestinal flora. The increase in the richness and diversity of the flora leads to the production of beneficial metabolites, which in turn inhibits the activation of the TLR4/NF-κB inflammatory pathway. This study provides a novel perspective on milk-derived peptide synergism with probiotics in alleviating UC.