The compounding roles of gut-immune-brain axis and COVID19 in manifestation of idiopathic Parkinson’s disease

Parkinson’s disease (PD), for long has been understood as a neurodegenerative disorder confined solely to the brain. It is now emerging as a systemic illness marked by early gastrointestinal, immune, and neuroendocrine perturbations. This review challenges the traditional neurocentric view of idiopathic PD (iPD), highlighting the gut- immune-brain axis as a central player in its pathogenesis. We have tried to explore how our dysbiosed gut, increased intestinal permeability, and immune hyperactivation orchestrate a cascade- from peripheral inflammation to microglial priming and α-synuclein aggregation thus leading to dopaminergic neurodegeneration. Intriguingly, the COVID-19 pandemic has amplified these mechanisms. SARS-CoV-2 not only perturbs gut ecology and immune signalling but may act as a hidden catalyst for parkinsonism. It can unmask or accelerate the diseased state through systemic inflammation, blood–brain barrier disruption, and HPA axis dysregulation. Strikingly, cases of post-COVID parkinsonism and symptom exacerbation in PD patients spotlight the virus as a potential environmental catalyst. By drawing parallels between post-COVID systemic disruption and the prodromal landscape of PD, we propose that the pandemic may be amplifying latent neurodegenerative pathways. Can pandemics act as silent accelerators of neurodegeneration, and are we equipped to detect their molecular footprints in time? This review synthesizes current evidence to reframe PD as a multisystem disorder, urging a shift toward integrative diagnostics and early peripheral interventions.