Objective: To determine how Parkinson’s disease (PD) medications influence gut microbiome composition and function, and to distinguish microbiome features associated with PD pathology from those related to medication exposure.

Background: Alterations in the gut microbiome have been consistently reported in PD. However, interpretation of these findings is challenging because many patients receive multiple dopaminergic and adjunctive medications, which may independently influence microbial communities. Clarifying the relative contributions of disease status and medication exposure is essential for identifying microbiome changes that are truly related to PD pathophysiology.

Method: We enrolled 87 patients with PD and 45 healthy controls. Clinical characteristics, disease severity, and detailed medication histories were obtained. Stool samples were collected from all participants and analyzed using shotgun metagenomic sequencing. Microbial taxonomic composition, diversity metrics, and functional pathways were compared while accounting for medication exposure, including amantadine, dopamine agonists, monoamine oxidase inhibitors, and catechol-O-methyltransferase inhibitors.

Results: Several PD medications were associated with significant shifts in gut microbial diversity. Amantadine use was linked to microbial profiles that more closely resembled those of healthy controls, whereas dopamine agonists were associated with divergence from control microbiome patterns. Independent of medication exposure, the genera Coprobacillus and Mogibacterium were consistently enriched in PD. In contrast, Coprobacter and Yeguiia were positively associated with amantadine and catechol-O-methyltransferase inhibitor use. Functional pathway analysis revealed enrichment of archaeatidylinositol biosynthesis and methanogenesis in PD regardless of medication status. Conversely, glucose degradation and 4-hydroxymandelate degradation pathways were reduced in association with medication exposure, suggesting medication-related shifts in microbial metabolic activity.

Conclusion: By incorporating medication exposure into microbiome analyses, we identified microbial taxa and functional pathways linked either to PD itself or to commonly used PD therapies. These findings highlight the importance of accounting for medication effects in microbiome studies and provide insights that may guide the development of microbiome-informed therapeutic strategies in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/disentangling-disease-and-medication-associated-gut-microbiome-signatures-in-parkinsons-disease/