Oxygen (O₂) availability is a key factor regulating microbiota composition and the homeostatic function of cells in the intestinal mucosa of vertebrates. Microbiota-derived metabolites increase O₂ consumption by intestinal epithelial cells (IECs), reducing its availability in the gut and leading to hypoxia. This physiological hypoxia activates cellular hypoxic sensors that adapt the metabolism and function of IECs and mucosa-resident cells, such as type-3 innate lymphoid cells (ILC3s). In this review, we discuss recent evidence suggesting that the intricate and multidirectional interactions among the microbiota, hypoxia/hypoxic sensors, and mammalian host cells (IECs and ILC3s) determine how the intestinal barrier and host–microbiota–pathogens connections are molded. Understanding these interactions might provide new treatment possibilities for dysbiosis, as well as certain inflammatory and infectious diseases.

氧气 (O ₂ ) 可用性是调节微生物群组成和脊椎动物肠粘膜细胞稳态功能的关键因素。微生物群衍生代谢物增加 O ₂肠上皮细胞 (IEC) 消耗，降低其在肠道中的可用性并导致缺氧。这种生理性缺氧会激活细胞缺氧传感器，从而适应 IEC 和粘膜驻留细胞（例如 3 型先天淋巴细胞 (ILC3)）的代谢和功能。在这篇综述中，我们讨论了最近的证据，这些证据表明微生物群、缺氧/缺氧传感器和哺乳动物宿主细胞（IEC 和 ILC3）之间复杂和多向的相互作用决定了肠道屏障和宿主-微生物群-病原体连接是如何形成的。了解这些相互作用可能会为生态失调以及某些炎症和传染病提供新的治疗可能性。