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.

Original languageEnglish
Pages (from-to)604-621
Number of pages18
JournalTrends in Immunology
Issue number7
StatePublished - Jul 2021


  • innate lymphoid cells
  • intestinal epithelial cells
  • microbiota
  • short-chain fatty acids


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