The nasal and gut microbiome in Parkinson's disease and idiopathic rapid eye movement sleep behavior disorder

Abstract

Background: Increasing evidence connects the gut microbiota and the onset and/or phenotype of Parkinson's disease (PD). Differences in the abundances of specific bacterial taxa have been reported in PD patients. It is, however, unknown whether these differences can be observed in individuals at high risk, for example, with idiopathic rapid eye movement sleep behavior disorder, a prodromal condition of α-synuclein aggregation disorders including PD.

Objectives: To compare microbiota in carefully preserved nasal wash and stool samples of subjects with idiopathic rapid eye movement sleep behavior disorder, manifest PD, and healthy individuals.

Methods: Microbiota of flash-frozen stool and nasal wash samples from 76 PD patients, 21 idiopathic rapid eye movement sleep behavior disorder patients, and 78 healthy controls were assessed by 16S and 18S ribosomal RNA amplicon sequencing. Seventy variables, related to demographics, clinical parameters including nonmotor symptoms, and sample processing, were analyzed in relation to microbiome variability and controlled differential analyses were performed.

Results: Differentially abundant gut microbes, such as Akkermansia, were observed in PD, but no strong differences in nasal microbiota. Eighty percent of the differential gut microbes in PD versus healthy controls showed similar trends in idiopathic rapid eye movement sleep behavior disorder, for example, Anaerotruncus and several Bacteroides spp., and correlated with nonmotor symptoms. Metagenomic sequencing of select samples enabled the reconstruction of genomes of so far uncharacterized differentially abundant organisms.

Conclusion: Our study reveals differential abundances of gut microbial taxa in PD and its prodrome idiopathic rapid eye movement sleep behavior disorder in comparison to the healthy controls, and highlights the potential of metagenomics to identify and characterize microbial taxa, which are enriched or depleted in PD and/or idiopathic rapid eye movement sleep behavior disorder. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Keywords: 16S rRNA gene amplicon sequencing; PD; RBD; genome reconstructions; nonmotor phenotype.

Figure 1

Overview of the observed community structures. (A) DNA yield per mL nasal wash or g of stool. (B) Estimates of OTU richness in nasal and gut samples. (C) The most common bacterial families and eukaryotic divisions or subdivisions in nasal and gut samples. Principal coordinate analyses of Jensen‐Shannon diversities between (D) OTU profiles of nasal and gut samples, (E) prokaryotic family profiles of nasal samples, and (F) OTU profiles of gut samples with circles around 70% confidence intervals for (E) sex (red, female; blue, male) and (F) study group (blue, healthy; red, PD; purple, iRBD). Colors and symbols used for the study participants throughout the articles are represented below. PC, principal coordinate.

Figure 2

Heatmaps of most differentially abundant taxa in PD patients and individuals with RBD. Relative abundances of prokaryotic OTUs and higher‐level taxa of the gut microbiome that were found to be differentially abundant in (A) PD patients, or (B) iRBD patients or both compared to the HCs (FDR‐adjusted DESeq2 P values < 0.001 and/or confirmation by ANCOM). Legends for the cohort‐related indications at the top of the heatmaps, for the summarizing heatmaps to the left, and for the central heatmaps are given to the left and below the heatmaps (for the complete set of differentially abundant taxa, detailed histograms, summary data, and further explanations, see Supplementary Information). For the OTUs, the lowest confident classifications are displayed; i.s.: incertae sedis; ^*the Bacteroides OTU_184 was found in both displayed sets. FC, fold change; n.a., not applicable.

Figure 3

Overviews of genomic reconstructions of two novel microbial populations depleted in patients with PD. (A) OTU_171, classified as Melainabacterium, (B) OTU_469, classified as alpha‐proteobacterium. 1) Contiguous sequences with lengths, 2) metagenomic depth of coverage, 3) % similarity to MelB1,57 4 and 5) predicted proteins colored according to functional categories, 6 and 7) tRNA and rRNA loci, and E) endoglucanase with synuclein‐like domain; pink spokes highlight unique essential genes, golden spokes highlight phylogenetic marker genes. kb = kilobase; tRNA, transfer RNA.