Aryl hydrocarbon receptor (AHR) and nuclear factor erythroid-derived 2-like 2 (NRF2): An important crosstalk in the...

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, mainly involved in detoxification. However, in the intestine, metabolites derived from the diet, which are converted by a wide range of bacteria can also activate the AHR. This intestinal AHR activation plays a key role in maintaining the gut barrier by, for example, upregulating antimicrobial peptides and anti-inflammatory cytokines. Since the gut barrier influences the gut-liver axis by regulating the leaking of metabolites, bacteria, and endotoxins into circulation and particularly into the liver, the AHR is a key factor in the gut-liver axis. Vice versa, certain liver pathologies also influence the gut microbiome, thereby altering bacteria-derived activation of the AHR. Additionally, bile acids can impact the gut via the liver and thereby also affect the AHR. The aryl hydrocarbon receptor (AHR) interacts with several molecular factors, one of which is the nuclear factor erythroid-derived 2-like 2 (NRF2), a transcription factor primarily associated with regulating antioxidant stress responses. The interplay between AHR and NRF2 has been investigated in the context of various diseases; this review highlights the significance of this interaction within the framework of the gut-liver axis.