Mucus produced by goblet cells in the gastrointestinal tract forms a biological barrier that protects the intestine from invasion by commensals and pathogens. However, the host-derived regulatory network that controls mucus secretion and thereby changes gut microbiota has not been well studied. Here, we identify that Forkhead box protein O1 (Foxo1) regulates mucus secretion by goblet cells and determines intestinal homeostasis. Loss of Foxo1 in intestinal epithelial cells (IECs) results in defects in goblet cell autophagy and mucus secretion, leading to an impaired gut microenvironment and dysbiosis. Subsequently, due to changes in microbiota and disruption in microbiome metabolites of short-chain fatty acids, Foxo1 deficiency results in altered organization of tight junction proteins and enhanced susceptibility to intestinal inflammation. Our study demonstrates that Foxo1 is crucial for IECs to establish commensalism and maintain intestinal barrier integrity by regulating goblet cell function.

中文翻译：

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Foxo1通过调节粘液分泌来控制肠道稳态和共生

胃肠道中杯状细胞产生的粘液形成生物屏障，保护肠道免受共生体和病原体的侵袭。然而，控制粘液分泌从而改变肠道微生物群的宿主衍生调节网络尚未得到很好的研究。在这里，我们确定叉头盒蛋白 O1 (Foxo1) 调节杯状细胞的粘液分泌并决定肠道稳态。肠上皮细胞 (IEC) 中 Foxo1 的缺失导致杯状细胞自噬和粘液分泌缺陷，从而导致肠道微环境受损和生态失调。随后，由于微生物群的变化和短链脂肪酸的微生物组代谢物的破坏，Foxo1 缺乏导致紧密连接蛋白的组织改变并增强了对肠道炎症的易感性。