Alpha-synuclein alters the faecal viromes of rats in a gut-initiated model of Parkinson’s disease
Stephen R. Stockdale, Lorraine A. Draper, Sarah M. O’Donovan, Wiley Barton, Órla O’Sullivan, Laura A. Volpicelli‐Daley, Aideen M. Sullivan, Cora O’Neill, Colin Hill
Abstract
Parkinson's disease (PD) is a chronic neurological disorder associated with the misfolding of alpha-synuclein (α-syn) into aggregates within nerve cells that contribute to their neurodegeneration. Recent evidence suggests α-syn aggregation may begin in the gut and travel to the brain along the vagus nerve, with microbes potentially a trigger initiating α-syn misfolding. However, the effects α-syn alterations on the gut virome have not been investigated. In this study, we show longitudinal faecal virome changes in rats administered either monomeric or preformed fibrils (PFF) of α-syn directly into their enteric nervous system. Differential changes in rat viromes were observed when comparing monomeric and PFF α-syn, with alterations compounded by the addition of LPS. Changes in rat faecal viromes were observed after one month and did not resolve within the study's five-month observational period. These results suggest that virome alterations may be reactive to host α-syn changes that are associated with PD development.