Parkinson’s disease (PD), the second most common neurodegenerative disorder, manifests with a wide range of motor and non-motor symptoms. A key pathological feature is the misfolding of alpha-synuclein proteins, which accumulate and contribute to PD symptomology. The body-first theory suggests this misfolding originates in the gut. However, the brain-first theory suggests that the misfolding originates in the olfactory bulb in the brain itself. Our hypothesis is that specific microorganisms (gut microbiome – body-first subtype, nasal microbiome – brain-first subtype) contribute to alpha-synuclein production/misfolding in these areas, potentially explaining the heterogeneity in PD symptoms. Research on PD microbiome has mainly targeted bacteria, yet the fungal community, or mycobiome, is also promising, as it plays roles in gut health, epithelial barrier support, and gut-brain communication. In the current project, we will explore for the first time the complex interaction between taxonomically detailed gut and nasal microbiome compositions (including both bacteria and fungi), brain connectivity, and clinical phenotyping as verified with sensitive motor assessments. This unique approach allows groundbreaking results that will improve understanding of the microbiome-gut-nasal brain interactions and their role(s) in the pathophysiology of PD to pave the way to therapeutics.