Emerging links between gut dysbiosis, aryl hydrocarbon receptor activation, and Parkinson's disease

Parkinson's disease (PD), the second most common progressive neurodegenerative disorder, is classically defined as a motor disorder characterized by dopaminergic neuron loss in the substantia nigra and motor dysfunction. Increasing evidence, however, identifies PD as a multisystem disorder with early non-motor features, including sleep, psychiatric, and gastrointestinal disturbances, implicating the gut-brain axis. Tryptophan metabolism through serotonin, kynurenine, and indole pathways generates bioactive metabolites, many of which regulate the aryl hydrocarbon receptor (AhR). AhR is a ligand-activated transcription factor involved in xenobiotic metabolism through canonical signaling pathways; however, growing evidence supports its role in immune balance, glial responses, and barrier integrity. Altered AhR signaling may therefore connect gut dysbiosis and disrupted tryptophan metabolism to sustained, systemic and central inflammation in PD. This review examines gut dysbiosis, tryptophan metabolism, and AhR signaling as potential mechanisms underlying idiopathic PD and highlights their relevance to early diagnosis and disease-modifying therapies.