Alleviative effects of whey protein hydrolysate against Dextran Sulfate Sodium-induced colitis via modulating the inflammatory response and gut microbiota

Whey protein peptides have been shown to have a variety of biological activities. This study aimed to investigate the preventive effect of Whey protein hydrolysate (WPH) on dextran sodium sulfate (DSS)-induced colitis in mice. The results showed that WPH has anti-inflammatory activity and preventive effect on colitis. WPH intervention was effective in delaying the development of colonic inflammation, reducing body weight changes, improving the histomorphology of the colon, protecting the colonic mucosal layer, and significantly reducing the levels of inflammatory factors in mice with colitis. In addition, high-dose WPH intervention increased the relative abundance of norank_f_Muribaculaceae by about 1.52-fold and decreased the relative abundance of Romboutsia and Enterobacter by about 3.77-fold and 2.45-fold, respectively, compared with the Model group. WPH also increased the levels of short-chain fatty acids, a metabolite of the intestinal flora. Mechanistic analysis showed that WPH reduced the disease severity in colitis mice mainly by reversing the imbalance of intestinal flora and regulating the MHC class I pathway. In conclusion, our study shows that WPH has anti-inflammatory activity and has a promising future in the prevention of colitis.