The gastric mucosa is a highly dynamic tissue that undergoes constant self-renewal through stem cell differentiation. Chief cells maintain a quiescent state in homeostasis but are responsible for regeneration after injury. Although the role of microbiome-host interactions in the intestine is well studied, less is known about these interactions in the stomach. Using the mouse organoid and germ-free mouse models, we show that microbiota-derived short-chain fatty acids (SCFAs) suppress the proliferation of chief cells in mice. This effect is mediated by activation of G-protein-coupled receptor 43. Most importantly, through metabolomics and transplantation studies, we show butyrate-producing Lactobacillus intestinalis modulates the proliferation of chief cells in mice. Our findings identify a mechanism by which the microbiota regulates the cell characteristics of chief cells, providing insight into the complex interplay between the host and its microbial environment and the mechanisms underlying gastric homeostasis, with potential therapeutic implications for gastric diseases.

中文翻译：

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微生物群衍生的短链脂肪酸决定了胃主细胞的干细胞特性


胃粘膜是一种高度动态的组织，通过干细胞分化不断进行自我更新。主细胞在体内平衡中保持静止状态，但负责损伤后的再生。尽管微生物组-宿主相互作用在肠道中的作用得到了很好的研究，但对胃中的这些相互作用知之甚少。使用小鼠类器官和无菌小鼠模型，我们表明微生物群衍生的短链脂肪酸 （SCFA） 抑制小鼠主要细胞的增殖。这种作用是由 G 蛋白偶联受体的激活介导的 43。最重要的是，通过代谢组学和移植研究，我们发现产生丁酸盐的肠乳杆菌可调节小鼠主细胞的增殖。我们的研究结果确定了微生物群调节主要细胞细胞特征的机制，为了解宿主与其微生物环境之间的复杂相互作用以及胃稳态的潜在机制提供了见解，对胃病具有潜在的治疗意义。