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Gut microbiome dysbiosis across early Parkinson's disease, REM sleep behavior disorder and their first-degree relatives.

ABSTRACT: The microbiota-gut-brain axis has been suggested to play an important role in Parkinson's disease (PD). Here we performed a cross-sectional study to profile gut microbiota across early PD, REM sleep behavior disorder (RBD), first-degree relatives of RBD (RBD-FDR), and healthy controls, which could reflect the gut-brain staging model of PD. We show gut microbiota compositions are significantly altered in early PD and RBD compared with control and RBD-FDR. Depletion of butyrate-producing bacteria and enrichment of pro-inflammatory Collinsella have already emerged in RBD and RBD-FDR after controlling potential confounders including antidepressants, osmotic laxatives, and bowel movement frequency. Random forest modelling identifies 12 microbial markers that are effective to distinguish RBD from control. These findings suggest that PD-like gut dysbiosis occurs at the prodromal stages of PD when RBD develops and starts to emerge in the younger RBD-FDR subjects. The study will have etiological and diagnostic implications.

SUBMITTER: Huang B

PROVIDER: S-EPMC10154387 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Gut microbiome dysbiosis across early Parkinson's disease, REM sleep behavior disorder and their first-degree relatives.

Huang Bei B Chau Steven W H SWH Liu Yaping Y Chan Joey W Y JWY Wang Jing J Ma Suk Ling SL Zhang Jihui J Chan Paul K S PKS Yeoh Yun Kit YK Chen Zigui Z Zhou Li L Wong Sunny Hei SH Mok Vincent C T VCT To Ka Fai KF Lai Hei Ming HM Ng Simon S Trenkwalder Claudia C Chan Francis K L FKL Wing Yun Kwok YK

Nature communications 20230502 1

The microbiota-gut-brain axis has been suggested to play an important role in Parkinson's disease (PD). Here we performed a cross-sectional study to profile gut microbiota across early PD, REM sleep behavior disorder (RBD), first-degree relatives of RBD (RBD-FDR), and healthy controls, which could reflect the gut-brain staging model of PD. We show gut microbiota compositions are significantly altered in early PD and RBD compared with control and RBD-FDR. Depletion of butyrate-producing bacteria ...[more]

PMID: 37130861

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Project description:ObjectivesTo develop a polysomnographic video-based scale for rating the severity of REM sleep behavior disorder (RBD), to classify the severity of RBD and to determine the intraindividual variability of RBD in patients with Parkinson disease (PD).MethodsTwenty PD patients identified with RBD were investigated with video-supported polysomnography (PSG). Seventy-three motor behavior events during REM sleep were graded visually and polysomnographically on an event-to-event basis according to categorical location of movements: "0" = no visible movement; "1" = slight movements or jerks "2" = movements involving proximal extremities, including violent behavior; "3" = axial involvement including bed falls. Vocalizations were rated as "1" for present or "0" for absent. Ratings were performed by 2 blinded raters. Reliability was calculated with Cohen's ?. Final RBD severity was determined by the highest score given. This rating scale was then used to compare RBD severity and density, calculated as RBD episodes per REM sleep minute over 2 consecutive nights in 10 additional PD patients with RBD. Statistical significance was determined by effect size (Hedges' g) and calculation of the confidence interval.ResultsInterrater reliability of the scale was 0.8 for movement data and 0.89 for vocalization data. Intraindividual RBD density varied significantly (effect size 0.5 ± 0.22; confidence interval 0.2 to 0.79) by factor 2.5 between the 2 PSG nights. Final RBD severity score differed in 60% of patients between nights 1 and 2. Forty percent of patients showed violent behavior, but only on one night. All patients had severely disturbed sleep with reduced sleep efficiency, loss of slow wave sleep, sleep fragmentation, and an increased periodic limb movement (PLM) index.ConclusionThe RBD severity scale (RBDSS) is a reliable, easy-to-use tool for assessing motor events during REM sleep with PSG. Severity and phenomenology of RBD shows a significant variability in the individual PD patient.

Project description:BackgroundIncreasing 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.ObjectivesTo 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.MethodsMicrobiota 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.ResultsDifferentially 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.ConclusionOur 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.

Dataset Information

Gut microbiome dysbiosis across early Parkinson's disease, REM sleep behavior disorder and their first-degree relatives.

Publications

Gut microbiome dysbiosis across early Parkinson's disease, REM sleep behavior disorder and their first-degree relatives.

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