Abstract
Parkinson’s disease (PD) is a common neurodegenerative disease characterized by chronic and progressive motor and cognitive symptoms. Currently, no cure for PD exists and risk factors that mediate susceptibility and progression are elusive. Investigation into the factors that lead to PD neuropathogenesis may provide therapeutic avenues for not only relieving motor and cognitive symptoms in patients, but also preventing their onset. Further, identification of a reliable biomarker for diagnosis may support intervention and monitoring of PD progression. In this study, we examined whether progressive motor and cognitive impairment in PD were associated with changes in gut microbiome diversity, taxa composition and function. Using sequenced 16S rRNA V4 regions of the gut microbiome of PD patients, we performed sex-controlled alpha and beta diversity correlations across cognitive and motor impairment PD severity metrics to uncover microbiome alterations associated with PD progression. We then analyzed compositional and taxa-level differences across sex-controlled severity metric groupings and determined whether identified microbiome alterations were functional in PD pathogenesis. Our findings show that motor impairment in PD correlated with increased gut microbiome diversity in males but not females. Conversely, cognitive impairment in PD did not correlate with altered gut microbiome composition in either sex. Further, we demonstrate that motor impairment corresponded with more core microbiome alterations than cognitive impairment in PD patients, and a sex-specific differential abundance of microbial taxa between moderate versus mild motor impaired PD patients. That said, observed compositional and taxa-level differences in motor impaired PD patients did not translate to functional changes with respect to predicted microbial pathways. Our work provides insight into possible biomarkers of motor impairment progression in PD patients and future directions for exploring microbiome alterations and their relationship with PD severity.