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Abstract

The Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet has garnered significant attention in recent years due to its correlations with a reduced risk of Alzheimer’s disease (AD) and cognitive decline. However, its effects in Parkinson’s disease (PD) remain relatively unexplored. Dietary patterns strongly influence the microbiome, and its mechanisms of action may thus be partially attributable to microbial shifts. PD, a neurodegenerative disorder characterized by motor and nonmotor symptoms, exhibits a gut microbial phenotype that is relatively consistent across previous studies, although species-level analyses are lacking. My thesis aimed to determine whether the MIND diet represents a dietary pattern of interest with respect to PD etiology, characterize the species-level microbial patterns associated with PD, and determine whether the observed MIND-related microbial differences correlate with PD outcomes. Gut metagenomic sequencing was performed on a human cohort (PD=200, Ctrl=100) and diet intakes were assessed using food frequency questionnaires. Disease severity was assessed using levodopa equivalent dose (LED) and the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Severity data was collected for 121 participants with PD over 5 years. MIND scores were strongly associated with later PD onset (P<0.006), especially in the female group, and weakly correlated with slower LED progression (Padj<0.08). Destabilization of the microbial network was observed in the PD group which corresponded to many taxonomic and functional differences, including a notable decrease in short-chain fatty acid producers and an increase in ribosomal genes. Random forest models suggested that these shifts were associated with faster disease progression. The MIND diet was primarily characterized by a reduction in pro-inflammatory serum C reactive protein (CRP) and an accompanying microbial pattern associated with lower CRP, both in PD and controls. People with PD whose microbiomes were categorized as significantly dysbiotic had lower MIND scores (P=0.004) and trended toward faster LED progression (P=0.13), though the latter association was underpowered and did not reach significance. Collectively, these findings support the MIND diet as a potential tool for reducing PD burden both pre- and post-PD diagnosis, and suggest that the underlying impact of the diet is related to the gut microbiome.