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.