Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China.
National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural, University, Nanjing, Jiangsu 210095, China.
Food Funct. 2024 Feb 5;15(3):1237-1249. doi: 10.1039/d3fo04152b.
Gut hormones are produced by enteroendocrine cells (EECs) found along the intestinal epithelium, and these cells play a crucial role in regulating intestinal function, nutrient absorption and food intake. A hydrolyzed casein diet has been reported to promote the secretion of gut hormones through the regulation of EEC development, but the underlying mechanism remains unclear. Therefore, this study was conducted to investigate whether the hydrolyzed casein diet can regulate EEC differentiation by employing mouse and organoid models. Mice were fed diets containing either casein (casein group) or hydrolyzed casein (hydrolyzed casein group) as the sole protein source. The hydrolyzed casein diet upregulated the expression of transcription factors, induced EEC differentiation, increased fasting serum ghrelin concentrations and promoted gastrointestinal (GI) motility in the duodenum compared to the casein diet. Interestingly, these differences could be abolished when there is addition of antibiotics to the drinking water, suggesting a significant role of gut microbiota in the hydrolyzed casein-mediated EEC function. Further investigation showed that the hydrolyzed casein diet led to reduced microbial diversity, especially the abundance of () on the duodenal mucosa. In contrast, gavage with impaired EEC differentiation through attenuated neurog3 transcription factor (Ngn3) expression, mediated through the promotion of Notch signaling. Moreover, pasteurized showed similar effects to enter organoids Overall, we found that a hydrolyzed casein diet reduced the abundance of and promoted Ngn3 controlling EEC differentiation and this pathway is associated with increased GI motility in mice. The findings provide new insights into the role of hydrolyzed casein in gut transit and guidelines for using hydrolyzed casein in safe formula milk.
肠激素由沿肠上皮分布的肠内分泌细胞（EEC）产生，这些细胞在调节肠道功能、营养吸收和食物摄入方面发挥着关键作用。有报道称，水解酪蛋白饮食通过调节 EEC 发育来促进肠激素的分泌，但潜在机制尚不清楚。因此，本研究通过使用小鼠和类器官模型来研究水解酪蛋白饮食是否可以通过调节 EEC 分化来发挥作用。将小鼠喂食仅含有酪蛋白（酪蛋白组）或水解酪蛋白（水解酪蛋白组）作为唯一蛋白质来源的饮食。与酪蛋白饮食相比，水解酪蛋白饮食上调了转录因子的表达，诱导了 EEC 分化，增加了空腹血清胃饥饿素浓度，并促进了十二指肠的胃肠道（GI）蠕动。有趣的是，当饮用水中添加抗生素时，这些差异可以被消除，这表明肠道微生物群在水解酪蛋白介导的 EEC 功能中起着重要作用。进一步的研究表明，水解酪蛋白饮食导致微生物多样性减少，特别是十二指肠黏膜上的丰度减少。相比之下，通过减弱神经调节蛋白 3 转录因子（Ngn3）的表达来抑制 EEC 分化，从而减弱 Notch 信号转导，灌胃 也会导致类似的效果。此外，巴氏杀菌的 对 enter 类器官也表现出类似的效果。总的来说，我们发现水解酪蛋白饮食减少了 的丰度，并促进了 Ngn3 控制 EEC 分化，这与小鼠 GI 蠕动增加有关。这些发现为水解酪蛋白在肠道转运中的作用提供了新的见解，并为在安全配方奶中使用水解酪蛋白提供了指导。
