Background PD may begin with the intestinal accumulation of α‐synuclein fibrils, which can be causally associated with gut dysbiosis. The variability of gut microbiota across countries prevented us from identifying shared gut dysbiosis in PD. Objectives To identify gut dysbiosis in PD across countries. Methods We performed 16S ribosomal RNA gene sequencing analysis of gut microbiota in 223 patients with PD and 137 controls, and meta‐analyzed gut dysbiosis by combining our dataset with four previously reported data sets from the United States, Finland, Russia, and Germany. We excluded uncommon taxa from our analyses. For pathway analysis, we developed the Kyoto Encyclopedia of Genes and Genomes orthology set enrichment analysis method. Results After adjusting for confounding factors (body mass index, constipation, sex, age, and catechol‐O‐methyl transferase inhibitor), genera Akkermansia and Catabacter, as well as families Akkermansiaceae, were increased, whereas genera Roseburia, Faecalibacterium, and Lachnospiraceae ND3007 group were decreased in PD. Catechol‐O‐methyl transferase inhibitor intake markedly increased family Lactobacillaceae. Inspection of these bacteria in 12 datasets that were not included in the meta‐analysis revealed that increased genus Akkermansia and decreased genera Roseburia and Faecalibacterium were frequently observed across countries. Kyoto Encyclopedia of Genes and Genomes orthology set enrichment analysis revealed changes in short‐chain fatty acid metabolisms in our dataset. Conclusions We report that intestinal mucin layer‐degrading Akkermansia is increased and that short‐chain fatty acid–producing Roseburia and Faecalibacterium are decreased in PD across countries. © 2020 International Parkinson and Movement Disorder Society

The effect of L-dihydroxyphenylalanine (L-DOPA) on extracellular dopamine (DA) in the striatum was determined by microdialysis in 6-hydroxydopamine (6-OHDA)-lesioned rats treated with and without the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). At the same time the intensity of L-DOPA-induced rotational behavior was assessed. In 6-OHDA-lesioned rats treated with 5,7-DHT, L-DOPA (50 mg/kg, i.p.) increased extracellular DA only to 20% of that measured in animals not treated with 5,7-DHT. Likewise, 6-OHDA-lesioned rats treated with 5,7-DHT exhibited a significantly lower number of L-DOPA-induced rotations. These results suggest that serotonergic terminals in the striatum can convert exogenously administered L-DOPA into DA that can be released into the extracellular space.

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BackgroundWe previously reported gut dysbiosis in patients with Parkinson’s disease (PD).ObjectiveThe aim of this study is to examine whether gut dysbiosis correlates with the progression of PD.MethodsWe examined changes in gut microbiota and demographic features in 2 years in 36 PD patients.ResultsA change of total UPDRS scores in 2 years was predicted by the counts of Bifidobacterium and Atopobium cluster at year 0 with a correlation coefficient of 0.52. Correlation analysis additionally revealed that low counts of Bifidobacterium and Bacteroides fragilis at year 0 were associated with worsening of UPDRS I scores in 2 years. In addition, low counts of Bifidobacterium at year 0 were associated with worsening of hallucinations/delusions in 2 years. Similarly, low counts of B. fragilis at year 0 were associated with worsening of motivation/initiative in 2 years. The patients were evenly divided into the deteriorated and stable groups based on the degree of worsening of total UPDRS scores. The deteriorated group had lower counts of Bifidobacterium, B. fragilis, and Clostridium leptium than the stable group at year 0 but not at year 2, suggesting that the deteriorated group may demonstrate accelerated lowering of these bacteria at year 0.ConclusionsThe total counts of intestinal bacterial decrease in the course of PD progression. Temporal profiles of lowering of bacterial counts are likely to be different from bacteria to bacteria, and also between the deteriorating and stable groups, which may be able to be exploited to differentiate patients with rapidly and slowly progressive PD pathology.

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