Gut Microbiota and Parkinson’s disease - a prospective analysis of the FINRISK 2002 Study

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Abstract Background Parkinson’s disease (PD) is a neurodegenerative movement disorder with mainly unknown etiology. Constipation is a common symptom, and changes in gut microbiota may play role in PD pathogenesis. Previous studies exploring microbial associations to PD have been mostly cross-sectional, and the role of microorganisms in PD etiology remains unclear. Thus, we examined the association between microbiota features and incident PD in a prospective cohort design. Methods In the FINRISK 2002 Study, 7231 participants gave a stool sample that underwent shotgun metagenomic sequencing. Participants with missing stool sample, incomplete covariate data, pregnancy, antibiotic use, and prevalent cases were excluded (final n = 5562). Cox regression models, adjusted for age, sex, education, smoking, coffee consumption, diabetes, cardiovascular events, and constipation, were used to assess associations between incident PD and microbiota features, ie. alpha diversity (the number of different species present in a sample), beta diversity (the differences in microbial composition between individuals), and abundance of 381 core taxa (compositional detection rate of at least 0.1% and a prevalence of 1%). 120 incident cases of PD, identified through register linkage, occurred during a median follow-up of 17.8 years. Results In the multivariate models, PD incidence was not associated with the Shannon index, a measure on alpha diversity, (p-value 0.81), or with the ten first principal component axes in beta diversity analysis (p-values ranging between 0.49-0.91). In permutational analysis, PD did not explain differences in the composition of the gut microbiota (R2 <0.001, p-value 0.46)). None of the core species were associated with PD incidence (all FDR-corrected p-values > 0.05). Conclusions This prospective study showed no support for an association between gut microbiota features and incident PD. Key messages • Previous findings associating gut microbiota with PD may be due to the cross-sectional design, ie. PD affecting the gut microbiota. • Suggestions to screen gut bacteria to identify people at high risk of Parkinson’s disease are vastly premature as the scientific evidence is inconclusive.

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