Integrated Multi-Cohort Analysis of the Parkinson's Disease Gut Metagenome
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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
Boktor JC, Sharon G, Verhagen Metman LA, Hall DA, Engen PA, Zreloff Z, Hakim DJ, Bostick JW, Ousey J, Lange D, Humphrey G, Ackermann G, Carlin M, Knight R, Keshavarzian A, Mazmanian SK
Journal
Movement disorders : official journal of the Movement Disorder Society
Year
2023
Keywords:
Parkinson's disease, dysbiosis, gut microbiome, microbial metabolism, shotgun metagenomics
BACKGROUND: The gut microbiome is altered in several neurologic disorders, including Parkinson's disease (PD). OBJECTIVES: The aim is to profile the fecal gut metagenome in PD for alterations in microbial composition, taxon abundance, metabolic pathways, and microbial gene products, and their relationship with disease progression. METHODS: Shotgun metagenomic sequencing was conducted on 244 stool donors from two independent cohorts in the United States, including individuals with PD (n = 48, n = 47, respectively), environmental household controls (HC, n = 29, n = 30), and community population controls (PC, n = 41, n = 49). Microbial features consistently altered in PD compared to HC and PC subjects were identified. Data were cross-referenced to public metagenomic data sets from two previous studies in Germany and China to determine generalizable microbiome features. RESULTS: We find several significantly altered taxa between PD and controls within the two cohorts sequenced in this study. Analysis across global cohorts returns consistent changes only in Intestinimonas butyriciproducens. Pathway enrichment analysis reveals disruptions in microbial carbohydrate and lipid metabolism and increased amino acid and nucleotide metabolism in PD. Global gene-level signatures indicate an increased response to oxidative stress, decreased cellular growth and microbial motility, and disrupted intercommunity signaling. CONCLUSIONS: A metagenomic meta-analysis of PD shows consistent and novel alterations in functional metabolic potential and microbial gene abundance across four independent studies from three continents. These data reveal that stereotypic changes in the functional potential of the gut microbiome are a consistent feature of PD, highlighting potential diagnostic and therapeutic avenues for future research. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Experiment 1
Reviewed Marked as Reviewed by Folakunmi on 2024-4-5
Subjects
- Location of subjects
- United States of America
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- 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,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,parkinson's disease
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- HC: household controls
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- PD: individuals with Parkinson's disease
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- cohort 1: movement disorder specialists examined and confirmed the diagnosis of all PD participants at a baseline screening. Parkinsonian symptoms were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr (H&Y) staging scale. cohort 2: PD participants were self-identified, verifying that they had received a PD diagnosis from a qualified physician.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 56
- Group 1 sample size Number of subjects in the case (exposed) group
- 88
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 12 weeks
Lab analysis
- Sequencing type
- WMS
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- Not specified
- 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).
- arcsine square-root
- Statistical test
- MaAsLin2
- 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
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-4-5
Source: Figure S2
Description: Summary of differential abundance results contrasting household controls and PD patients.
Abundance in Group 1: increased abundance in PD: individuals with Parkinson's disease
| NCBI | Quality Control | Links |
|---|---|---|
| Verrucomicrobiota |
Revision editor(s): Idiaru angela
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-4-5
Source: Figure S2
Description: Summary of differential abundance results contrasting household controls and PD patients.
Abundance in Group 1: decreased abundance in PD: individuals with Parkinson's disease
| NCBI | Quality Control | Links |
|---|---|---|
| Roseburia |
Revision editor(s): Idiaru angela
Experiment 2
Reviewed Marked as Reviewed by Folakunmi on 2024-4-5
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- PC: healthy population controls without Parkinson's Disease
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- PD: Individuals with Parkinson's disease
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- cohort 1: movement disorder specialists examined and confirmed the diagnosis of all PD participants at a baseline screening. Parkinsonian symptoms were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr (H&Y) staging scale. cohort 2: PD participants were self-identified, verifying that they had received a PD diagnosis from a qualified physician.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 83
Lab analysis
Statistical Analysis
- Matched on Factors on which subjects have been matched on in a case-control study
- age, body mass index, race, sex
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-4-5
Source: Figure 2 & figure S2
Description: Summary of differential abundance results contrasting healthy population controls and PD patients.
Abundance in Group 1: increased abundance in PD: Individuals with Parkinson's disease
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomycetota | ||
| Eisenbergiella | ||
| Eisenbergiella tayi | ||
| Ruthenibacterium | ||
| Ruthenibacterium lactatiformans |
Revision editor(s): Idiaru angela, Folakunmi
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-4-5
Source: Figure 2 & figure S2
Description: Summary of differential abundance results contrasting healthy population controls and PD patients.
Abundance in Group 1: decreased abundance in PD: Individuals with Parkinson's disease
| NCBI | Quality Control | Links |
|---|---|---|
| Faecalibacterium prausnitzii | ||
| Firmicutes bacterium CAG:95 | ||
| Lachnospira eligens | ||
| Faecalibacterium | ||
| Butyrivibrio |
Revision editor(s): Idiaru angela, Folakunmi
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