Nutritional intervention studies to influence the gut microbiome and improve Parkinson's disease

Abstract

Non-invasive microbiome-derived multi-omic biomarkers for the early-stage detection and stratification of Parkinson's disease (PD) revealed a bacterial dysbiosis in early and prodromal PD with an increased abundance of e.g. Akkermansia spp., that increase the permeability of the gut by degrading the mucus barrier through regulation of tight junctions. The mucus erosion of the gut epithelial layer leads to increased gut permeability which favors inflammatory responses by pathogenic and/or toxin intrusions. Additionally microbiome-derived metabolites are involved in neuroinflammatory and/or neurotoxic processes in PD, that can foster the spreading of α-synuclein aggregates and neuronal damage. In multiple animal models, restructuring of the gut microbiome by dietary interventions (resistant starch or fasting regimens) restores the intestinal mucus barrier and prolongs survival. In human studies, high fiber diet/resistant starch impacts the human gut microbiome, metaproteome and metabolome, restores the mucus barrier and can thereby improve the glucose and lipid metabolism. In our PD cohort we have observed correlations of inflammation markers, i.e. IL-17A or CCL20 in plasma with operational taxonomic units. We also identified correlations when comparing the microbiome data to clinical parameters, such as UPDRS scores. Under high-fiber diet regimen we identified changes in microbiome within 24 h by increasing the Shannon diversity, short chain fatty acids and various metabolites. Increasing evidence in humans also suggest, that intermittent fasting regiments may directly influence the gut microbiota and its metabolic function and secondarily impact peripheral and central inflammation. We will present data of our short- and longterm dietary interventional trials in PD.