Metagenomics of Parkinson's disease implicates the gut microbiome in multiple disease mechanisms
From BugSigDB
Jump to:navigation, search
Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Wallen ZD, Demirkan A, Twa G, Cohen G, Dean MN, Standaert DG, Sampson TR, Payami H
Journal
Nature communications
Year
2022
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.
Statistical test
ANCOM
Experiment 1
Subjects
- Location of subjects
- United States of America
- Host species Species from which microbiome was sampled (if applicable)
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Parkinson's disease IDIOPATHIC PARKINSON DIS,Idiopathic Parkinson Disease,Idiopathic Parkinson's Disease,IDIOPATHIC PARKINSONS DIS,Idiopathic PD,LEWY BODY PARKINSON DIS,Lewy Body Parkinson Disease,Lewy Body Parkinson's Disease,Paralysis agitans,paralysis agitans,PARKINSON DIS,PARKINSON DIS IDIOPATHIC,Parkinson disease,Parkinson Disease, Idiopathic,Parkinson syndrome,Parkinson's,Parkinson's disease,Parkinson's disease (disorder),Parkinson's disease NOS,Parkinson's disease NOS (disorder),Parkinson's Disease, Idiopathic,Parkinson's Disease, Lewy Body,Parkinson's syndrome,Parkinsonian disorder,Parkinsonism, Primary,Parkinsons,PARKINSONS DIS,PARKINSONS DIS IDIOPATHIC,PARKINSONS DIS LEWY BODY,Parkinsons disease,Primary Parkinsonism
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy controls.
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Parkinson's Disease subjects.
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Potential PD cases for enrollment were identified via systematic pre-screening of electronic medical records (EMR) of patients with an upcoming appointment in the Movement Disorder Clinic at UAB. Subjects were invited to enroll in the study after their clinic visit if the attending specialist confirmed PD diagnosis and the patient was willing to hear about the study.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 234
- Group 1 sample size Number of subjects in the case (exposed) group
- 490
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- N/A
Lab analysis
- Sequencing type
- WMS
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.1
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Yes
- Matched on Factors on which subjects have been matched on in a case-control study
- Matched on: "Environmental effects" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.Environmental effects
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- Confounders controlled for: "stool sample collection method" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.stool sample collection method, Confounders controlled for: "total sequence count per sample" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.total sequence count per sample
Signature 1
Source: Supplementary Figure 4. Species correlation networks for PD and neurologically healthy controls.
Description: PD metagenome network with species that emerged from MWAS(ANCOM-BC) as having significantly higher abundance in PD than NHC are colored blue, and those that had significantly lower abundance in PD than NHC colored red.
Abundance in Group 1: increased abundance in Parkinson's Disease subjects.
Revision editor(s): Fcuevas3
Signature 2
Source: Supplementary Figure 4. Species correlation networks for PD and neurologically healthy controls.
Description: PD metagenome network with species that emerged from MWAS as having significantly higher abundance in PD than NHC are colored blue, and those that had significantly lower abundance in PD than NHC colored red.
Abundance in Group 1: decreased abundance in Parkinson's Disease subjects.
Revision editor(s): Fcuevas3
Retrieved from "https://bugsigdb.org/w/index.php?title=Study_746&oldid=109973"
Hidden category:
