Objective: To determine the gut microbiome composition of treatment-naïve de novo Parkinson’s disease (PD) patients.

Background: Over fifteen studies have independently demonstrated gut dysbiosis in PD. However, these studies mainly concerned established PD cases and can be confounded by disease duration and the use of dopaminergic medication. Here, we present the first results of the two largest gut microbiome cohorts in treatment-naïve de novo PD patients to date.

Method: Sequencing of the V4 variable region of the 16S rRNA-gene was performed on stool samples of two cohorts: (1) the Dutch Parkinson Cohort (DUPARC) consisting of 138 PD patients and 85 healthy controls (HCs), with 45 spousal HCs; and (2) the Finnish Cohort, combined of three Finnish microbiome studies, consisting of 58 PD patients and 89 HCs, with 2 spousal HCs. DNA extraction was performed using the Qiagen Allprep kit and the PSP Spin Stool kit for DUPARC and the Finnish Cohort respectively. A subset of DUPARC samples was extracted using both methods. Library preparation was performed in a randomized manner and samples of both cohorts were sequenced all together in the same sequencing runs.
Dissimilarities in overall gut microbiome composition (i.e. Beta diversity) were calculated using Bray-Curtis dissimilarities. Statistical significance was tested using a PERMANOVA, adjusted for age, sex and cohort.

Results: Preliminary analysis indicates a marked difference in overall gut microbiome composition between the two cohorts (R2=0.036, p<0.0001). Nonetheless, a statistically significant difference was found between de novo PD patients and HCs after adjusting for age, sex and cohort (R2=0.0062, p<0.0001). When analyzing both studies separately, there was still a statistically significant difference between de novo PD patients and HCs after adjusting for age and sex, with a larger contribution of PD status in the Finnish Cohort (R2=0.014, p=0.0002) than DUPARC (R2=0.0068, p=0.013).

Conclusion: Preliminary analyses of the two largest gut microbiome cohorts in de novo PD suggest that gut dysbiosis is already present in the early stages of PD, without the possible confounding influences of dopaminergic medication. Changes in gut microbiome composition were present in both cohorts, though more pronounced in the Finnish Cohort. This might be related to the larger number of same household spousal HCs in DUPARC.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/evidence-of-gut-dysbiosis-in-treatment-naive-de-novo-parkinsons-disease/