Interactions of Gut Microbiome, Genetic Susceptibility, and Environmental Factors in Parkinson's Disease
Technical Report,01 Sep 2018,31 Aug 2019
University of Alabama at Birmingham Birmingham United States
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Genetic and environmental factors explain a fraction of Parkinsons disease risk, prompting the question if the microorganisms in the gut hold the trigger. Attempts to identify PD-associated microorganisms have produced inconsistent results. It is unknown if low reproducibility can be overcome by rigorous study design or its unsurmountable due to dynamic nature of microbiome. Our aim was to determine if it is possible to attain robust and reproducible association signal with gut microorganisms. If so, to identify the microorganisms responsible for the dysbiosis in Parkinsons. We adopted standards of rigor from GWAS, used two datasets for validation, sequenced 16S rRNA V4-region using DNA from stool, investigated 46 potential confounders, conducted microbiome-wide association study with two methods ANCOM, Kruskal-Wallis, followed by co-occurrence network analysis to infer interactions. 15 genera were associated with Parkinsons at microbiome-wide significance level, in both datasets, with both methods, with or without covariate adjustment. The associations were not independent, rather represented 3 polymicrobial clusters. Cluster 1 was composed of opportunistic pathogens all we reelevated in PD. Cluster 2 were short-chain-fatty-acid producing bacteria all were reduced in PD. Cluster 3 were carbohydrate metabolizer probiotics elevated in PD. In conclusion, robust, reproducible results are attainable. Over abundance of pathogens in PD gut is a novel finding and their identity provides the lead to experimentally test their role in triggering disease.
- Medicine and Medical Research