Presented by: Natalia Palacios
Funding Sources for study: This study was funded by NIH (R01NS097723; PI: Palacios).
Objective: Prior studies on the gut microbiome in Parkinson’s disease (PD) have yielded conflicting results, and few studies have focused on prodromal (premotor) PD or used metagenomic profiling. We conducted a nested case-control study within two large epidemiological cohorts to examine the role of the gut microbiome in PD.
Methods: We profiled the fecal metagenomes of 420 participants in the Nurses’ Health Study and the Health Professionals Follow-up Study with recent onset PD (N = 75), with features of prodromal PD (N = 101), controls with constipation (N = 113), and healthy controls (N = 131) to identify microbial taxonomic and functional features associated with PD and PPS. We conducted omnibus and feature-wise analyses to identify bacterial species and pathways associated with prodromal and recently onset PD.
Results: We observed depletion of several strict anaerobes associated with production of anti-inflammatory short-chain fatty acids among participants with PD or features of prodromal PD. A microbiome-based classifier had moderate power (AUC = 0.76 for species and 0.74 for pathways) to discriminate between recently onset PD cases and controls. These taxonomic shifts corresponded with functional shifts indicative of alternative in carbohydrate degradation. Similar, but less marked, changes were observed in people with PPS, in both microbial features and functions.
Interpretation: In this study nested within two large cohorts with rich covariate data and rigorous PD identification, we observed that PD and PPS were associated with similar changes in the gut microbiome. These findings suggest that changes in the microbiome could represent novel biomarkers for the earliest phases of PD.