Parkinson’s Disease Dampens the Impact of Mental Health on Microbial Predicted Metabolic Functions

Abstract

Parkinson’s Disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. Out of all the neurodegenerative diseases investigated to date, PD has the strongest association with gut microbiota alterations. The gut microbiota of PD patients consistently shows a reduction in carbohydrate fermentation and increased production of deleterious amino acid metabolites compared to healthy controls. Interestingly, mental health problems such as depression, anxiety, and poor sleep often co-occur with PD, on top of being prodromal symptoms that can appear a decade prior to disease onset. Although depression, anxiety, and poor sleep each have gut microbiota alterations in the absence of PD, the impact of these conditions on the predicted gut function of individuals with PD is not well known. This present study investigates the compositional and functional metabolic alterations underlying depression, anxiety, and poor sleep co-occurring with PD. Alpha and beta diversity analysis showed no significant difference for all mental health factors. Minor alterations were observed at the taxonomic level, with Verrucomicrobiota being uniquely identified in PD patients experiencing co-occurring poor sleep. Functional analysis using PICRUSt2 showed a reduction in metabolic pathway alterations for PD patients with co-occurring depression. Anxiety was associated with subtle functional changes that were more similar than different between PD individuals and healthy controls. Lastly, significant alterations were identified for individuals experiencing poor sleep. Overall, this study suggests that PD dampens the functional impact of mental health conditions on the gut microbiota, highlighting the volatility of the PD microbiota and need for further function-based investigations.