Shotgun Metagenomic Profiling of the Gut Virome in Prodromal and Confirmed Parkinson's Disease.

We conducted a nested case-control study within the Nurses' Health Study and the Health Professionals Follow-up Study to examine the role of the gut virome (GV) in Parkinson's disease (PD). We applied a novel metagenomic virome profiling approach, Bioinformatic Application for Quantification and Labeling of Viral taxonomy (BAQLaVa), to prospectively collected metagenomic data from 62 participants with PD, 123 healthy controls, and 90 participants with prodromal PD (pPD). Multivariate linear modeling identified 3 viral genome bins (VGBs) that were elevated in PD: MVG081219 (β = 0.86, q = 0.013), MVG041501 (β = 0.95, q = 0.048), MVG081211 (β = 0.66, q = 0.048) and one VGB, MVG098915 (β = -1.42, q = 0.047) that was depleted in participants with PD compared to controls. These four VGBs were similarly associated with pPD. This work suggests that the GV has potential as a future biomarker for PD. ANN NEUROL 2026;100:334-340.