Evidence map›Paper›PMID 36376318›Full record

ArticleNature communications2022

Metagenomics of Parkinson's disease implicates the gut microbiome in multiple disease mechanisms.

Zachary D Wallen, Ayse Demirkan, Guy Twa, Gwendolyn Cohen, Marissa N Dean, David G Standaert, Timothy R Sampson, Haydeh Payami

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 220 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
220citing papers in PubMed, 5 pooled it
33.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

220 citing papers in PubMed, 5 syntheses or guidelines pooled it, 305 citations in OpenAlex.

  1. Beyond bacteria: a multi-omics view of the gut-brain axis in Parkinson's disease.Frontiers in cellular and infection microbiology · 2026
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  14. The microbiota-proteostasis axis: implications in neurodegenerative diseases.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026
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160 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 2 countries.

Zachary D WallenDepartment of Neurology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.ORCID 0000-0002-2278-7348
Ayse DemirkanSurrey Institute for People-Centred AI, University of Surrey, Guildford, Surrey, GU2 7XH, UK.
Guy TwaDepartment of Neurology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.
Gwendolyn CohenDepartment of Neurology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.ORCID 0000-0002-5084-061X
Marissa N DeanDepartment of Neurology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.
David G StandaertDepartment of Neurology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.ORCID 0000-0003-2921-8348
Timothy R SampsonAligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA.
Haydeh PayamiDepartment of Neurology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA. haydehpayami@uabmc.edu.ORCID 0000-0001-9084-5338
University of Alabama at Birmingham · USEmory University · USUniversity of Alabama at Birmingham Hospital · USUniversity of Surrey · GB

Funding

Interaction of Pyrethroid Exposure and the Microbiome on Parkinson's Disease related PathologiesR01ES032440 · NIEHS · EMORY UNIVERSITY · PI Timothy Robert Sampson · 2022 to 2026
$1.7M
UAB Training Program In NeuroscienceT32NS095775 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Erik D Roberson · 2017 to 2026
$1.6M
NIEHS NIH HHS R01 ES032440NINDS NIH HHS T32 NS095775
6 · The paper itself

Abstract

Parkinson's disease (PD) may start in the gut and spread to the brain. To investigate the role of gut microbiome, we conducted a large-scale study, at high taxonomic resolution, using uniform standardized methods from start to end. We enrolled 490 PD and 234 control individuals, conducted deep shotgun sequencing of fecal DNA, followed by metagenome-wide association studies requiring significance by two methods (ANCOM-BC and MaAsLin2) to declare disease association, network analysis to identify polymicrobial clusters, and functional profiling. Here we show that over 30% of species, genes and pathways tested have altered abundances in PD, depicting a widespread dysbiosis. PD-associated species form polymicrobial clusters that grow or shrink together, and some compete. PD microbiome is disease permissive, evidenced by overabundance of pathogens and immunogenic components, dysregulated neuroactive signaling, preponderance of molecules that induce alpha-synuclein pathology, and over-production of toxicants; with the reduction in anti-inflammatory and neuroprotective factors limiting the capacity to recover. We validate, in human PD, findings that were observed in experimental models; reconcile and resolve human PD microbiome literature; and provide a broad foundation with a wealth of concrete testable hypotheses to discern the role of the gut microbiome in PD.

Indexed as

Gastrointestinal MicrobiomeParkinson DiseaseDysbiosisHumansMetagenomeMetagenomics

Identifiers

PMID36376318
PMCPMC9663292
OpenAlexW4309109636

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.