Abstract
BackgroundParkinson’s disease (PD) presently is conceptualized as a protein aggregation disease in which pathology involves both the enteric and the central nervous system, possibly spreading from one to another via the vagus nerves. As gastrointestinal dysfunction often precedes or parallels motor symptoms, the enteric system with its vast diversity of microorganisms may be involved in PD pathogenesis. Alterations in the enteric microbial taxonomic level of L-DOPA-naïve PD patients might also serve as a biomarker.MethodsWe performed metagenomic shotgun analyses and compared the fecal microbiomes of 31 early stage, L-DOPA-naïve PD patients to 28 age-matched controls.ResultsWe found increased Verrucomicrobiaceae (Akkermansia muciniphila) and unclassified Firmicutes, whereas Prevotellaceae (Prevotella copri) and Erysipelotrichaceae (Eubacterium biforme) were markedly lowered in PD samples. The observed differences could reliably separate PD from control with a ROC-AUC of 0.84. Functional analyses of the metagenomes revealed differences in microbiota metabolism in PD involving the ẞ-glucuronate and tryptophan metabolism. While the abundances of prophages and plasmids did not differ between PD and controls, total virus abundance was decreased in PD participants. Based on our analyses, the intake of either a MAO inhibitor, amantadine, or a dopamine agonist (which in summary relates to 90% of PD patients) had no overall influence on taxa abundance or microbial functions.ConclusionsOur data revealed differences of colonic microbiota and of microbiota metabolism between PD patients and controls at an unprecedented detail not achievable through 16S sequencing. The findings point to a yet unappreciated aspect of PD, possibly involving the intestinal barrier function and immune function in PD patients. The influence of the parkinsonian medication should be further investigated in the future in larger cohorts.
Highlights
Parkinson’s disease (PD) presently is conceptualized as a protein aggregation disease in which pathology involves both the enteric and the central nervous system, possibly spreading from one to another via the vagus nerves
In his original thesis work in 1913, already identified the dorsal motor nucleus of the vagus as a hotspot of brain pathology and Braak et al more recently confirmed the early involvement of the vagus and hypothesized that PD might originate in the gut and that α-syn aggregation might spread via vagal structures into the central nervous system (CNS) and higher cortical regions [3]
Using ANCOM, we found genera Akkermansia, Prevotella, Eubacterium, unknown Bacteria, and unknown Firmicutes to be significantly different between PD and control patients
Summary
Parkinson’s disease (PD) presently is conceptualized as a protein aggregation disease in which pathology involves both the enteric and the central nervous system, possibly spreading from one to another via the vagus nerves. LB are present in the central nervous system (CNS) and in the enteric nervous system (ENS) of the entire gastrointestinal tract, corresponding to the clinical notion that the gastrointestinal tract is involved in PD [2] Lewy, in his original thesis work in 1913, already identified the dorsal motor nucleus of the vagus as a hotspot of brain pathology and Braak et al more recently confirmed the early involvement of the vagus and hypothesized that PD might originate in the gut and that α-syn aggregation might spread via vagal structures into the CNS and higher cortical regions [3]. Additional yet unidentified factors beyond α-syn must be involved in the presumed PD disease process
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