Alterations of the gut virome in patients with Parkinson's disease.

Gut microbiota plays a pivotal role in Parkinson's disease (PD) pathogenesis. However, the role of enteric viruses remains underexplored. Here, we reanalyzed publicly available metagenomic datasets from two independent cohorts, including 79 PD patients and 79 controls, to characterize gut virome profiles and explore the potential role of enteric viruses in PD pathogenesis and early diagnosis. Our findings indicate increased richness and diversity of the gut virome in PD, with 640 vOTUs differing in abundance between groups. Notably, Siphoviridae and Myoviridae were more abundant in PD patients. A variety of viruses enriched in PD or healthy subjects (HS) preferentially infect bacterial hosts that produce short-chain fatty acids. Furthermore, specific viral functional orthologs, such as thymidylate synthase (K00560) and integrases (K14059), displayed notable differences in prevalence between PD-enriched and HS-enriched vOTUs. Finally, we constructed a random forest model using the top 22 most significant vOTUs, which achieved an AUC of 0.822, demonstrating strong performance in distinguishing PD patients from healthy controls. This is the first study to characterize the gut virome profile in PD, laying a robust foundation for future investigations into the underlying mechanisms and early diagnosis strategies for PD as well as other neurodegenerative disorders.