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

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Abstract Parkinson's disease (PD) ranks as the second most prevalent neurodegenerative disorder, following Alzheimer's disease, and it has a significant link to the gut bacteriome. However, the relationship between PD and gut virome is unclear. To explore the gut virome's traits in PD, we analyzed the gut viral communities of 89 PD patients and 89 healthy individuals, utilizing metagenome-wide analysis of fecal metagenomes from two accessible public datasets. Our findings indicate that PD patients exhibit a marked increase in gut viral richness and diversity, alongside significant shifts in the overall viral composition. At the family level, PD patients showed elevated levels of Siphoviridae, Myoviridae, p-crAss-like, Podoviridae, Salasmaviridae, Circoviridae, and Herelleviridae, coupled with a reduced presence of Quimbyviridae. We identified 640 vOTUs that were differentially abundant between patients and controls, including a notable increase in Siphoviridae and Myoviridae viruses in PD patients. Interestingly, PD-enriched vOTUs predominantly infected a diverse array of bacterial hosts, including but not limited to Alistipes, Lawsonibacter, Oscillibacter, Faecalibacterium, Ruthenibacterium, Intestinimonas, Flavonifractor and Fournierella. Conversely, the major hosts for the HS-enriched vOTUs were primarily Bacteroides and Prevotella species. Additionally, certain viral functional orthologs, such as thymidylate synthase (K00560) and integrases (K14059), exhibited significant differences in prevalence between PD-enriched and HS-enriched vOTUs, highlighting the potential functional impact of these PD-associated viruses. Moreover, we developed classification models using gut viral signatures to distinguish PD patients from healthy subjects, achieving an optimal area under the receiver operator characteristic curve (AUC) of up to 0.854. The models also demonstrated high accuracy in predicting independent samples. This underscores the gut virome's clinical potential as a diagnostic tool for PD. This study pinpointed viral signatures that distinguish significantly between Parkinson's Disease (PD) patients and healthy subjects (HS), and showed that these distinctive viral markers hold promise as novel targets for PD intervention. This study lays a foundation for future research into the mechanisms and treatment strategies of this and potentially other autoimmune diseases.

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