Dopaminergic Therapeutics for Treating Parkinson’s Disease Were Associated with a Shift in the Gut Microbiota to Resemble Healthy Individuals

Abstract

Parkinson’s Disease (PD) is a neurodegenerative disorder associated with dopaminergic neuron loss, leading to dopamine dysregulation. Dopaminergic therapeutics are often administered to restore dopamine levels and have been associated with changes to the gut microbiota. Through a secondary data analysis of a cross-sectional cohort of PD patients, we aimed to investigate changes in the gut microbiome associated with the use of four dopaminergic drugs (entacapone, pramipexole, rasagiline, amantadine). Although the use of dopaminergic therapeutics was not associated with compositional alterations to the microbial diversity of PD patients, we observed changes to specific taxa. Amantadine and pramipexole therapeutics were both associated with a core microbiome that contains Faecalibacterium – a genus contained in the core microbiome of healthy individuals but absent in untreated PD patients. Furthermore, entacapone and amantadine use was associated with taxa that are indicative of a healthy gut microbiome, including Lachnospiraceae and Colidextribacter. We also identified three genera that were differentially abundant with dopaminergic drug use. Dopaminergic therapeutic use was generally associated with increased Bifidobacterium, decreased Prevotella, and increased Akkermansia. While increased Bifidobacterium is associated with a healthier gut microbiome and Akkermansia is associated with gut dysbiosis, the effects of Prevotella remain unclear. Our findings suggest that dopaminergic therapeutics are associated with alterations in the gut microbiome of PD patients that provide an overall benefit to the host. Future studies could incorporate higher resolution analysis at the species level and explore causational effects of dopaminergic drugs in a prospective study.