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Background: This study aims to identify distinct microbial and functional biomarkers characteristic of body-first or brain-first subtypes of Parkinson's disease (PD). This could illuminate the unique pathogenic mechanisms within these subtypes., Methods: In this cross-sectional study, we classified 36 well-characterized PD patients into body-first, brain-first, or undetermined subtypes based on the presence of premotor REM sleep behavior disorder (RBD) and cardiac meta-iodobenzylguanidine (MIBG) uptake. We then conducted an in-depth shotgun metagenomic analysis of the gut microbiome for each subtype and compared the results with those from age- and sex-matched healthy controls., Results: Significant differences were found in the gut microbiome of body-first PD patients (n = 15) compared to both brain-first PD patients (n = 9) and healthy controls. The gut microbiome in body-first PD showed a distinct profile, characterized by an increased presence of Escherichia coli and Akkermansia muciniphila, and a decreased abundance of short-chain fatty acid-producing commensal bacteria. These shifts were accompanied by a higher abundance of microbial genes associated with curli protein biosynthesis and a lower abundance of genes involved in putrescine and spermidine biosynthesis. Furthermore, the combined use of premotor RBD and MIBG criteria was more strongly correlated with these microbiome differences than the use of each criterion independently., Conclusions: Our findings highlight the significant role of dysbiotic and pathogenic gut microbial alterations in body-first PD, supporting the body-first versus brain-first hypothesis. These insights not only reinforce the gut microbiome's potential as a therapeutic target in PD but also suggest the possibility of developing subtype-specific treatment strategies., Competing Interests: Declaration of competing interest Eun Jeong Lee reports financial support was provided by Korea Ministry of Science and ICT. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The vast majority of Parkinson's disease (PD) cases are of sporadic origin and despite extensive research in recent years, the etiology still remains unclear. Several current case control studies are aiming to characterize a putative PD-specific composition of the gut microbiome, reflecting the potential relevance of microbiota in the pathogenesis of PD. Although methodologies and cohort sizes differed, the currently available studies showed reproducible or consistent results in terms of PD-specific alterations to the intestinal bacteria. By applying metagenomic sequencing procedures, it is even possible to distinguish PD cases from healthy individuals at a very early disease stage by means of individually modified microbiota. Among others, microbiota that are associated with an altered intestinal barrier or immune function, such as Akkermansia, Lactobacillus, Faecalibacterium and Prevotella were significantly over-represented or under-represented. There may even be a prodromal microbiome, as a comparable microbial shift is also found in patients with rapid eye movement (REM) sleep behavior disorder (RBD), a risk factor for the later development of synucleinopathies, such as PD.

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., (© 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.)