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

Agradecimentos: This study was supported by National Institutes of Health (1R01DK126969-01) and Fundação de Amparo à Pesquisa do Estado de São Paulo (18/15313–8). The study was also financed by the National Council for Scientific and Technological Development (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES)–Finance Code 001.L.P.P., J.L.F., and R.O.C are recipients of fellowships from FAPESP (2018/02208–1, 2017/06577–9, and 2016/23142-3, respectively). M.C. was supported by MIST (U01AI095542 Abstract: 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 andmultidirectional interactions among themicrobiota, 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 FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES Fechado