Comparison of phage and plasmid populations present in the gut microbiota of Parkinson’s disease patients

The aging population worldwide is on the rise, leading to a higher number of Parkinson’s disease (PD) cases each year. PD is presently the second most prevalent neurodegenerative disease, affecting an estimated 7-10 million individuals globally. This research aimed to identify mobile genetic elements in human fecal samples using a shotgun metagenomics approach. We found over 44,000 plasmid contigs and compared plasmid populations between PD patients (n = 68) and healthy controls (n = 68). Significant associations emerged between Body Mass Index (BMI) and plasmid alpha diversity. Moreover, the gene populations present on plasmids displayed marked differences in alpha and beta diversity between PD patients and healthy controls. We identified a considerable number of phage contigs that were differentially abundant in the two groups. Moreover, we improved the continuity and identification of the protein coding regions of the phage contigs by implementing alternative genetic codes. We built a classification system based on a selection of the phages differentially abundant in the groups. A machine learning approach based on phage abundances allowed a classification of the subjects into the PD or control group with an area under curve (AUC) of 0.969. ### Competing Interest Statement FS received grants from the Academy of Finland, the Hospital District of Helsinki and Uusimaa, the OLVI Foundation, Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, the Wilhelm and Else Stockmann Foundation, the Emil Aaltonen Foundation, the Yrjo Jahnsson Foundation and the Sigrid Juselius Foundation, Renishaw. Honoraria: AbbVie, Axial Biotherapeutics, Orion, GE Healthcare, Merck, Teva, Bristol Myers Squibb, Sanofi, Biocodex, Lundbeck, and Biogen. FS is th founder and CEO of NeuroInnovation Oy and NeuroBiome Ltd. and is a member of the advisory boards of Axial Biotherapeutics and MRM Health. He has stock options from Axial Biotherapeutics. P.A.B.P., L.P., P.A., and F.S. have patents issued (FI127671B, US10139408B2, US11499971B2) and pending (US16/186,663, EP3149205) that are assigned to NeuroBiome Ltd. T.K.S. was funded by the Novo Nordisk Foundation (NNF22OC0080109).