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.乳清蛋白肽已被证实具有多种生物学活性。本研究旨在探究乳清蛋白水解物（Whey protein hydrolysate, WPH）对葡聚糖硫酸钠（dextran sodium sulfate, DSS）诱导的小鼠结肠炎的预防作用。结果显示，WPH具备抗炎活性，对结肠炎具有预防效果。WPH干预可有效延缓结肠炎症的进展，改善小鼠体质量变化情况，优化结肠组织形态学结构，保护结肠黏膜层，并显著降低结肠炎小鼠体内的炎症因子水平。此外，与模型组相比，高剂量WPH干预可使未分类Muribaculaceae科（norank_f_Muribaculaceae）的相对丰度提升约1.52倍，分别使罗姆布茨菌属（Romboutsia）与肠杆菌属（Enterobacter）的相对丰度降低约3.77倍与2.45倍。WPH还可提升肠道菌群代谢产物短链脂肪酸的水平。机制分析表明，WPH主要通过逆转肠道菌群失衡、调控主要组织相容性复合体I类（MHC class I）通路，以减轻结肠炎小鼠的疾病严重程度。综上，本研究证实WPH具备抗炎活性，在结肠炎预防领域具有良好的应用前景。