Metagenomic Analysis Reveals Large-Scale Disruptions of the Gut Microbiome in Parkinson's Disease
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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
Metcalfe-Roach A, Cirstea MS, Yu AC, Ramay HR, Coker O, Boroomand S, Kharazyan F, Martino D, Sycuro LK, Appel-Cresswell S, Finlay BB
Journal
Movement disorders : official journal of the Movement Disorder Society
Year
2024
Keywords:
Parkinson's disease, metagenomics, microbiome
BACKGROUND: Parkinson's disease (PD) has been consistently linked to alterations within the gut microbiome. OBJECTIVE: Our goal was to identify microbial features associated with PD incidence and progression. METHODS: Metagenomic sequencing was used to characterize taxonomic and functional changes to the PD microbiome and to explore their relation to bacterial metabolites and disease progression. Motor and non-motor symptoms were tracked using Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and levodopa equivalent dose across ≤5 yearly study visits. Stool samples were collected at baseline for metagenomic sequencing (176 PD, 100 controls). RESULTS: PD-derived stool samples had reduced intermicrobial connectivity and seven differentially abundant species compared to controls. A suite of bacterial functions differed between PD and controls, including depletion of carbohydrate degradation pathways and enrichment of ribosomal genes. Faecalibacterium prausnitzii-specific reads contributed significantly to more than half of all differentially abundant functional terms. A subset of disease-associated functional terms correlated with faster progression of MDS-UPDRS part IV and separated those with slow and fast progression with moderate accuracy within a random forest model (area under curve = 0.70). Most PD-associated microbial trends were stronger in those with symmetric motor symptoms. CONCLUSION: We provide further evidence that the PD microbiome is characterized by reduced intermicrobial communication and a shift to proteolytic metabolism in lieu of short-chain fatty acid production, and suggest that these microbial alterations may be relevant to disease progression. We also describe how our results support the existence of gut-first versus brain-first PD subtypes. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Experiment 1
Reviewed Marked as Reviewed by Svetlana up on 2025-3-3
Subjects
- Location of subjects
- Canada
- 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
- Healthy Controls (Ctrl)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Parkinson’s disease patients (PD patients - Assymetric)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Parkinson’s disease patients (PD patients) refers to participants with PD; who had developed motor symptoms ≤12 years before initial study participation (mean, 6 ± 3 years). Asymmetric motor phenotypes were defined as those with absolute differences above the median.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 100
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 3 months
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).
- centered log-ratio
- Statistical test
- Mann-Whitney (Wilcoxon)
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
- Matched on Factors on which subjects have been matched on in a case-control study
- age
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-3-3
Source: Fig. S3
Description: Differential abundance of taxa between Control and PD
Abundance in Group 1: increased abundance in Parkinson’s disease patients (PD patients - Assymetric)
| NCBI | Quality Control | Links |
|---|---|---|
| Collinsella aerofaciens | ||
| Ruthenibacterium lactatiformans | ||
| Blautia obeum |
Revision editor(s): KateRasheed
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-3-3
Source: Fig. S3
Description: Differential abundance of taxa between Control and PD
Abundance in Group 1: decreased abundance in Parkinson’s disease patients (PD patients - Assymetric)
| NCBI | Quality Control | Links |
|---|---|---|
| Blautia wexlerae | ||
| Roseburia inulinivorans | ||
| Roseburia hominis | ||
| Faecalibacterium prausnitzii |
Revision editor(s): KateRasheed
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2025-3-3
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Parkinson’s disease patients (PD patients - Symmetric)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- A "symmetric motor phenotype" in Parkinson's disease (PD) refers to a presentation where the motor symptoms like tremor, rigidity, and bradykinesia are equally present on both sides of the body, meaning the disease affects both sides of the body almost identically
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-3-3
Source: Fig. S3
Description: Differential abundance of taxa between Control and PD
Abundance in Group 1: increased abundance in Parkinson’s disease patients (PD patients - Symmetric)
| NCBI | Quality Control | Links |
|---|---|---|
| Blautia obeum | ||
| Collinsella aerofaciens | ||
| Alistipes indistinctus | ||
| Coprococcus catus | ||
| Ruthenibacterium lactatiformans |
Revision editor(s): KateRasheed
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-3-3
Source: Fig. S3
Description: Differential abundance of taxa between Control and PD
Abundance in Group 1: decreased abundance in Parkinson’s disease patients (PD patients - Symmetric)
| NCBI | Quality Control | Links |
|---|---|---|
| Roseburia hominis | ||
| Roseburia intestinalis | ||
| Roseburia inulinivorans | ||
| Blautia wexlerae | ||
| Faecalibacterium prausnitzii |
Revision editor(s): KateRasheed
Experiment 3
Reviewed Marked as Reviewed by Svetlana up on 2025-3-3
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Parkinson’s disease patients (PD patients)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Parkinson’s disease patients (PD patients) refers to participants with PD; who had developed motor symptoms ≤12 years before initial study participation (mean, 6 ± 3 years).
- Group 1 sample size Number of subjects in the case (exposed) group
- 176
Lab analysis
Statistical Analysis
- Statistical test
- Kruskall-Wallis
- MaAsLin2
- ANCOM-BC
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Yes
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- sex, sequence read depth, Confounders controlled for: "laxative use" 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.laxative use
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-3-3
Source: Fig. 2A
Description: Differentially abundance of species between healthy controls and PD patients using ANCOM-BC, MaAsLin2, and ALDEx2 (after controlling for confounders).
Abundance in Group 1: increased abundance in Parkinson’s disease patients (PD patients)
| NCBI | Quality Control | Links |
|---|---|---|
| Coprococcus catus | ||
| Ruthenibacterium lactatiformans | ||
| Alistipes indistinctus | ||
| Blautia obeum |
Revision editor(s): KateRasheed
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-3-3
Source: Fig. 2A
Description: Differentially abundance of species between healthy controls and PD patients using ANCOM-BC, MaAsLin2, and ALDEx2 (after controlling for confounders).
Abundance in Group 1: decreased abundance in Parkinson’s disease patients (PD patients)
| NCBI | Quality Control | Links |
|---|---|---|
| Roseburia inulinivorans | ||
| Roseburia intestinalis | ||
| Blautia wexlerae |
Revision editor(s): KateRasheed
Experiment 4
Reviewed Marked as Reviewed by Svetlana up on 2025-3-3
Differences from previous experiment shown
Subjects
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- Not specified
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-3-3
Source: Fig. 2A
Description: Differentially abundance of species between healthy controls and PD patients using ANCOM-BC, MaAsLin2, and ALDEx2.
Abundance in Group 1: increased abundance in Parkinson’s disease patients (PD patients)
| NCBI | Quality Control | Links |
|---|---|---|
| Alistipes indistinctus | ||
| Blautia obeum | ||
| Collinsella aerofaciens | ||
| Coprococcus catus | ||
| Ruthenibacterium lactatiformans |
Revision editor(s): KateRasheed
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-3-3
Source: Fig. 2A
Description: Differentially abundance of species between healthy controls and PD patients using ANCOM-BC, MaAsLin2, and ALDEx2.
Abundance in Group 1: decreased abundance in Parkinson’s disease patients (PD patients)
| NCBI | Quality Control | Links |
|---|---|---|
| Blautia wexlerae | ||
| Faecalibacterium prausnitzii | ||
| Roseburia hominis | ||
| Roseburia intestinalis | ||
| Roseburia inulinivorans |
Revision editor(s): KateRasheed
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