7246185
doi
10.5281/zenodo.7246185
oai:zenodo.org:7246185
user-asaphub
Ayse Demirkan
University of Surrey
Guy Twa
University of Alabama at Birmingham
Gwendolyn Cohen
University of Alabama at Birmingham; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network
Marissa N Dean
University of Alabama at Birmingham
David G Standaert
University of Alabama at Birmingham
Timothy Sampson
Emory University School of Medicine; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network
Haydeh Payami
University of Alabama at Birmingham; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network
Metagenomics of Parkinson's disease implicates the gut microbiome in multiple disease mechanisms
Zachary D Wallen
University of Alabama at Birmingham; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network
bioproject:PRJNA834801
info:eu-repo/semantics/openAccess
Creative Commons Attribution 4.0 International
https://creativecommons.org/licenses/by/4.0/legalcode
metagenomics
Parkinson's disease
gut microbiome
inflammation
opportunistic pathogens
short-chain fatty acids
lipopolysaccharides
dopamine
GABA
glutamate
serotonin
nicotinamide
curli
alpha-synuclein
toxicant
probiotics
<p><strong>Abstract:</strong> 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 at species and genus level, followed by network analysis to identify polymicrobial clusters, and functional profiling based on microbial genes and pathways. 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. </p>
<p><strong>Zenodo contents:</strong> In this Zenodo archive we provide (1) post sequence QC and post taxonomic and functional profiling "Source Data" used to generate tables and figures in the manuscript and (2) "Supplementary Code" that contains the workflow and code used to perform bioinformatic processing of shotgun sequences and statistical analyses of microbial profiles and subject metadata. The code provided here is the same "Supplementary Code" that is provided in the supplement of the manuscript. Individual level raw shotgun sequences and metadata are available on NCBI Sequence Read Archive (SRA) under BioProject ID <a href="https://www.ncbi.nlm.nih.gov/bioproject/834801">PRJNA834801</a>.</p>
This work was funded by The U.S. Army Medical Research Materiel Command endorsed by the U.S. Army through the Parkinson's Research Program Investigator-Initiated Research Award under Award No. W81XWH1810508; NIH Training Grant T32NS095775; NIH/NIEHS 1R01ES032440-01A1 and Parkinson's Foundation PF-SF-JFA-830658; and Aligning Science Across Parkinson's [ASAP-020527] through the Michael J. Fox Foundation for Parkinson's Research. For the purpose of open access, at the time of publication, the authors have applied a CC BY public copyright license to all Author Accepted Manuscripts arising from this submission.
Zenodo
2022-10-26
info:eu-repo/semantics/other
7246184
user-asaphub
1666837589.645341
580742
md5:732c6273349d7a2efc0bc7d13d0c7d69
https://zenodo.org/records/7246185/files/Supplementary_Code_24Oct2022.zip
52098767
md5:4672da6a00ae951281441dd0a1620fdd
https://zenodo.org/records/7246185/files/Source_Data_24Oct2022.xlsx
public
PRJNA834801
Cites
bioproject
10.5281/zenodo.7246184
isVersionOf
doi