Bacteriophages: Are They an Overlooked Driver of Parkinson's Disease? George Tetz MD, PhD1,*, Victor Tetz1 MD, PhD 1Human Microbiology Institute, NY, NY 10027 *g.tetz@hmi-us.com Background: We have recently shown for the first time that phages may be implicated as a previously overlooked in the development of multifactorial diseases, including those associated with increased intestinal permeability and protein misfolding. The objective of this study was to evaluate the phagobiota of patients with Parkinson's disease (PD) and its interplay with the bacterial component of the microbiota, and to reveal hallmark alterations in bacteriophage composition that may be implicated in PD onset or progression. Methods:To explore bacterial and bacteriophage community compositions associated with PD, we used shotgun metagenomics sequencing data of fecal microbiome from 32 patients with PD and 28 controls. Gut microbiota composition was analyzed with MethaPLan and Metavir tools.
Results:We identified hallmark alterations in bacteriophage composition that may be implicated in the onset or progression of PD. We found significant decreases in Lactococcus spp., Streptococcus spp., and Lactobacillus spp. in PD. There were numerous alterations in phage contents in PD patients that reshaped microbiota of PD patients, in a manner that might have a functional role in disease onset and progression. Notably, we observed a more than 10-fold decrease in Lactococcus spp. abundance in patients with PD compared to controls, due to the increased abundances of strictly virulent phages from the c2-like and 936-like groups. These phages are most frequently isolated from the dairy-containing products. Our data indicate that depletion of Lactococcus spp. in patients with PD can be explained by the appearance of these environmental lytic phages. In turn, Lactococcus bacteria play an important role in gut-microbiota axis, being an important source of microbiota-derived neurochemicals such as dopamine and having a particular influence on ENS, which plays a primary role in PD. Lactococci are also known as important regulators of gut permeability, alterations in which are also implicated in PD pathogenesis. Conclusions:This is the first study to suggest a link between bacteriophages and PD. Our study suggests the necessity to pay attention to bacteriophages (including environmental phages) in human health as possible previously overlooked human pathogens.
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