Host-microbiota interactions: a novel insight into the aryl hydrocarbon receptor in Parkinson's disease

Parkinson's disease (PD) is regarded as the second most common neurodegenerative disease. Accumulating evidence suggested an emerging effect of the dysregulation of the gut-brain axis in the neurodegenerative disease pathogenesis, mediated particularly by microbiota-derived metabolites in PD. The aryl hydrocarbon receptor (AHR) is of great importance in regulating central nervous system inflammation by sensing microbiota-derived metabolites.

AHR is a transcription factor activated by ligands, which can be activated locally or remotely by endogenous microbial metabolites. AHR signaling suppressed inflammation by activating anti-inflammatory and immunosuppressive responses, promoting intestinal host-microbiome homeostasis. The pathogenesis of PD is related to the activation of microglia and the occurrence of neuroinflammation. There is increasing attention that alterations in the intestinal flora and decreased AHR activity were closely associated with PD.

The AHR-gut microbiota axis garnered increasing attention in PD research. In this review, we synthesize current clinical and preclinical evidence linking the AHR-gut microbiota axis to PD pathogenesis, and we highlight that pharmacological targeting of this pathway represents an emerging therapeutic strategy for PD.