Hypoxia Inducible Factor-1α: The Curator of Gut Homeostasis

Abstract

The human gut microbiome is a stratified and resilient ecosystem co-inhabited by a diverse and dynamic pool of microorganisms. Microbial selection, establishment, and colonization are modulated through a complex molecular network of host-microbial interactions. These molecular bioprocesses ensure the taxonomic composition of the mature human gut microbiome. The human gut microbiome plays a vital role in host health; otherwise, any microbial dysbiosis could predispose to the onset of physiological and metabolic disorder/s. Focussed research are being carried out to identify key molecular agents defining gut homeostasis. These molecules hold the potential to develop effective therapeutic solutions for microbial dysbiosis-associated human disorders. Of these, Hypoxia-inducible factor-1α (HIF-1α) is a central player in host-microbial crosstalk to maintain gut homeostasis. Human gut microbial metabolites regulate its cellular stability, which in turn regulates various cellular processes required for the stable gut microbiome. In the present review, an effort has been made to summarize the key role of HIF-1α to maintain gut homeostasis. HIGHLIGHTS-Explain the molecular process of host microbial molecular interactions.-Establish the explicit role of HIF-1α in intestinal epithelial integrity and gut health.-Regulation of HIF-1α by human gut commensals and vice a versa.-Regulation of the host immune response for survival and colonization of human gut commensal.

Overview of the rules of the microbial engagement in the gut microbiome: a step towards microbiome therapeutics

“…Immunological oxidative burst and damaged gut epithelial lining induce temporal gut microbial dysbiosis (Kiely et al 2018). However, removal of pathogens with anti-infective therapy downregulates NF-jB mediated host innate immunological response (Headland and Norling 2015) and stabilizes HIF-1a for the maintenance of gut epithelial integrity (Kumar et al 2020). Normalized gut epithelium allows the successful re-establishment of the gut microbes (Kumar et al 2020).…”

“…However, removal of pathogens with anti-infective therapy downregulates NF-jB mediated host innate immunological response (Headland and Norling 2015) and stabilizes HIF-1a for the maintenance of gut epithelial integrity (Kumar et al 2020). Normalized gut epithelium allows the successful re-establishment of the gut microbes (Kumar et al 2020). These studies indicate that for the successful survival as a gut commensal, a microbe has to evolve various strategies to escape host immune response.…”

“…The utilization of the butyrate induces oxygen depletion within the gut epithelial cells (Litvak et al 2018). The resultant hypoxic condition induces the expression of hypoxia-inducible factor 1a (HIF1a) (Palazon et al 2014;Kumar et al 2020). The HIF1a acts as a transcriptional regulator for claudin-1 that maintains the tight junctions and epithelial cell integrity (Saeedi et al 2015).…”

“…Normalized gut epithelium allows the successful re‐establishment of the gut microbes (Kumar et al . 2020). These studies indicate that for the successful survival as a gut commensal, a microbe has to evolve various strategies to escape host immune response.…”

“…2014; Kumar et al . 2020). The HIF1α acts as a transcriptional regulator for claudin‐1 that maintains the tight junctions and epithelial cell integrity (Saeedi et al .…”