Host/microbiota interactions-derived tryptophan metabolites modulate oxidative stress and inflammation via aryl hydrocarbon receptor signaling

Abstract

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that induces the expression of a broad range of downstream genes such as cytochromes P450 enzymes and cyclooxygenase-2. Recent research focuses are shifting from AhR activation induced by xenobiotics to its response patterns to physiological ligands that expand our understanding of how endogenous metabolites as ligands to modulate AhR signaling pathway under homeostasis and pathological conditions. With increasing interest in AhR and its endogenous ligands, it would seem advisable to summarize a variety of endogenous ligands especially host/gut microbiota-derived tryptophan metabolites. Mounting evidence has indicated that AhR play a critical role in the regulation of redox homeostasis and immune responses. In this review, we outline the canonical and non-canonical AhR signalling pathway that is mediated by host/gut microbiota-derived tryptophan metabolites. Through several typical endogenous AhR ligands, we investigated the molecular mechanisms of AhR-induced oxidative stress and inflammation in the pathological milieu, including diabetes, diabetic kidney disease and end-stage renal disease. Finally, we summarize and emphasize the limitations and breakthrough of endogenous AhR ligands from host/microbial tryptophan catabolites. This review might provide novel diagnostic and prognostic approach for refractory human diseases and establish new therapeutic strategies for AhR activation.

Keywords: Aryl hydrocarbon receptor; Gut microbiota; Oxidative stress and inflammation; Redox homeostasis; Tryptophan metabolites.