Hypoxia and HIF-1 as key regulators of gut microbiota and host interactions

Oxygen (O2) availability is a key factor regulating microbiota composition and the homeostatic function of cells in the intestinal mucosa of vertebrates. Microbiotaderived 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.

Automated summary

Oxygen availability is crucial for microbiota composition and cellular function in the gut, with metabolites from microbiota affecting oxygen consumption. The interactions among microbiota, hypoxia/hypoxic sensors, and mammalian host cells play a key role in shaping intestinal barrier and host-microbiota-pathogens connections. Understanding these interactions may lead to new treatment options for dysbiosis and certain inflammatory and infectious diseases.