Hypoxia-inducible factor 1-alpha (HIF-1α) acts as a transcription factor that regulates cellular adaptation to low oxygen levels and supports the development and function of the gut barrier, thereby conferring protection against IBD (55), while constitutive activation of HIF-2α leads to the development or exacerbation of IBD in colitis models (56). Here, EPAS1 is linked to inflammatory bowel disease.