Article
Gut microbiota dysbiosis in Parkinson’s disease – a systematic review and pooled analysis
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Published: | August 19, 2022 |
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Introduction: While the role of the gut microbiome in the pathogenesis of Parkinson’s disease (PD) is under intense investigation, the results presented in the literature are still very heterogeneous. These discrepancies arise not only from the highly heterogeneous pathology of PD, but also from widely varying methodologies at all stages of the workflow, from sampling to final statistical analysis. The aim of the present work is to harmonize the workflow across studies to reduce the methodological heterogeneity and to perform a pooled analysis to account for other sources of heterogeneity.
Method: We performed a systematic review to identify studies comparing the gut microbiota of PD patients to healthy controls and requested the original patient-level data. We obtained data of nine studies with 1843 observations (1092 PD patients and 751 non-PD cases) in total. A workflow was designed to harmonize processing across these nine studies from bioinformatics processing to final statistical analysis. This allowed for an unbiased comparison of alpha and beta diversity between studies. Furthermore, it enabled the possibility for a pooled analyses of differential abundance using a Bayesian random-effects model based on individual patient-level data. To test the robustness of the obtained results, the analyses were confirmed with a two-stage meta-analysis approach using ANCOM-BC.
Results: The results show no evidence for systematic changes in alpha diversity in PD patients. In line with the results of the original publications, beta diversity analyses revealed systematic differences between PD patients and healthy controls. However, differences between studies were substantially greater, even after harmonizing bioinformatics workflows. The pooled analyses reduced the evidence of differential abundant taxa from 63 (as reported in the literature) to only seven genera and one family (14 taxa in total).
Discussion: The results show that harmonizing workflows minimizes differences between statistical methods and reveals only a small set of taxa being associated with the pathogenesis of PD. Especially, increased shares of the genera Akkermansia and Bifidobacterium and decreased shares of the genera Roseburia and Faecalibacterium were characteristic for PD-associated microbiota. Those genera are associated with reduced mucosal barrier and inflammatory states in the intestine and are potentially important biomarkers.
Conclusion: Our study summarizes evidence that reduced levels of butyrate producing taxa in combination with possible degradation of the mucus layer by Akkermansia may promote intestinal inflammation and reduced permeability of the gut mucosal layer. This in turn may allow potentially pathogenic metabolites to transit and enter the enteric nervous system. Future prospective long-term cohort studies are important to disentangle the causal mechanisms involved in the observed dysbiosis in the gut microbiota, and to further evaluate the potential of the microbiota as a biomarker for PD. We will publish the harmonization workflow in an open-access repository so that researchers can use it for their meta-analyses.
The authors declare that they have no competing interests.
The authors declare that an ethics committee vote is not required.