Changes in Gastrointestinal Microbiome Composition in PD: A Pivotal Role of Covariates
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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 Uniform resource identifier for web resources.
Authors
Cosma-Grigorov A, Meixner H, Mrochen A, Wirtz S, Winkler J, Marxreiter F
Journal
Frontiers in neurology
Year
2020
Keywords:
Parkinson's disease, biomarker, constipation, covariates, gut, microbiome, non-motor symptoms
Altered gut microbiota may trigger or accelerate alpha-synuclein aggregation in the enteric nervous system in Parkinson's disease (PD). While several previous studies observed gut microbiota alterations in PD, findings like diversity indices, and altered bacterial taxa itself show a considerable heterogeneity across studies. We recruited 179 participants, of whom 101 fulfilled stringent inclusion criteria. Subsequently, the composition of the gut microbiota in 71 PD patients and 30 healthy controls was analyzed, sequencing V3-V4 regions of the bacterial 16S ribosomal RNA gene in fecal samples. Our goal was (1) to evaluate whether gut microbiota are altered in a southern German PD cohort, (2) to delineate the influence of disease duration, stage, and motor impairment, and (3) to investigate the influence of PD associated covariates like constipation and coffee consumption. Aiming to control for a large variety of covariates, strict inclusion criteria were applied. Finally, propensity score matching was performed to correct for, and to delineate the effect of remaining covariates (non-motor symptom (NMS) burden, constipation, and coffee consumption) on microbiota composition. Prior to matching altered abundances of distinct bacterial classes, orders, families, and genera were observed. Both, disease duration, and stage influenced microbiome composition. Interestingly, levodopa equivalent dose influenced the correlation of taxa with disease duration, while motor impairment did not. Applying different statistical tests, and after propensity score matching to control for NMS burden, constipation and coffee consumption, Faecalibacterium and Ruminococcus were most consistently reduced in PD compared to controls. Taken together, similar to previous studies, alterations of several taxa were observed in PD. Yet, further controlling for PD associated covariates such as constipation and coffee consumption revealed a pivotal role of these covariates. Our data highlight the impact of these PD associated covariates on microbiota composition in PD. This suggests that altered microbiota may mediate the protective effect of i.e., coffee consumption and the negative effect of constipation in PD.
Experiment 1
Reviewed Marked as Reviewed by KateRasheed on 2025-6-12
Subjects
- Location of subjects
- Germany
- 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
- Control group
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Parkinson's disease (PD) group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with Parkinson's disease
- Group 0 sample size Number of subjects in the control (unexposed) group
- 31
- Group 1 sample size Number of subjects in the case (exposed) group
- 70
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 1 month
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V3-V4
- 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
- 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)?
- Yes
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Reviewed Marked as Reviewed by KateRasheed on 2025-6-12
Source: Figure 2A & Supplementary Figure 3A-D
Description: Heat tree analysis depicting alterations in microbiota composition between PD and controls.
Abundance in Group 1: increased abundance in Parkinson's disease (PD) group
| NCBI | Quality Control | Links |
|---|---|---|
| Alcaligenaceae | ||
| Betaproteobacteria | ||
| Burkholderiales | ||
| Oscillospira | ||
| Sutterella | ||
| Sutterellaceae |
Signature 2
Reviewed Marked as Reviewed by KateRasheed on 2025-6-12
Source: Figure 2A & Supplementary Figure 3A-D
Description: Heat tree analysis depicting alterations in microbiota composition between PD and controls.
Abundance in Group 1: decreased abundance in Parkinson's disease (PD) group
| NCBI | Quality Control | Links |
|---|---|---|
| Bacillota | ||
| Clostridia | ||
| Clostridiaceae | ||
| Eubacteriales | ||
| Faecalibacterium | ||
| Lachnospiraceae | ||
| Fusicatenibacter | ||
| Gemmiger | ||
| Lachnospiraceae incertae sedis |
Experiment 2
Reviewed Marked as Reviewed by KateRasheed on 2025-6-12
Differences from previous experiment shown
Subjects
Lab analysis
Statistical Analysis
- Statistical test
- Random Forest Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Reviewed Marked as Reviewed by KateRasheed on 2025-6-12
Source: Figure 2B
Description: Unsupervised random forests classification using PD and controls as classes and abundances as classifiers along a decision tree.
Abundance in Group 1: increased abundance in Parkinson's disease (PD) group
| NCBI | Quality Control | Links |
|---|---|---|
| Sutterella | ||
| Akkermansia | ||
| Bilophila | ||
| Butyricimonas | ||
| Dehalobacterium | ||
| Phascolarctobacterium |
Revision editor(s): Victoria
Signature 2
Reviewed Marked as Reviewed by KateRasheed on 2025-6-12
Source: Figure 2B
Description: Unsupervised random forests classification using PD and controls as classes and abundances as classifiers along a decision tree.
Abundance in Group 1: decreased abundance in Parkinson's disease (PD) group
| NCBI | Quality Control | Links |
|---|---|---|
| Faecalibacterium | ||
| Oscillospira | ||
| Ruminococcus | ||
| Blautia |
Revision editor(s): Victoria
Experiment 3
Differences from previous experiment shown
Subjects
- Group 0 sample size Number of subjects in the control (unexposed) group
- 19
- Group 1 sample size Number of subjects in the case (exposed) group
- 28
Lab analysis
Statistical Analysis
- Statistical test
- Mann-Whitney (Wilcoxon)
- Matched on Factors on which subjects have been matched on in a case-control study
- Matched on: "coffee consumption" 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.coffee consumption, constipation
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- Confounders controlled for: "NMS score" 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.NMS score, Confounders controlled for: "Wexner Constipation Score" 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.Wexner Constipation Score, Confounders controlled for: "coffee consumption" 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.coffee consumption
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Reviewed Marked as Reviewed by KateRasheed on 2025-6-12
Source: Figure 4 a&b
Description: Differences in microbiota after matching for obstipation and coffee consumption.
Abundance in Group 1: decreased abundance in Parkinson's disease (PD) group
| NCBI | Quality Control | Links |
|---|---|---|
| Ruminococcus |
Revision editor(s): Victoria
Experiment 4
Reviewed Marked as Reviewed by KateRasheed on 2025-6-12
Differences from previous experiment shown
Subjects
Lab analysis
Statistical Analysis
- Statistical test
- Random Forest Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Reviewed Marked as Reviewed by KateRasheed on 2025-6-12
Source: Figure 4c
Description: Random forests classification of differences in microbiota after matching for obstipation and coffee consumption.
Abundance in Group 1: increased abundance in Parkinson's disease (PD) group
| NCBI | Quality Control | Links |
|---|---|---|
| Prevotella | ||
| Sutterella | ||
| Akkermansia |
Revision editor(s): Victoria
Signature 2
Reviewed Marked as Reviewed by KateRasheed on 2025-6-12
Source: Figure 4C
Description: Random forests classification of differences in microbiota after matching for obstipation and coffee consumption.
Abundance in Group 1: decreased abundance in Parkinson's disease (PD) group
| NCBI | Quality Control | Links |
|---|---|---|
| Ruminococcus | ||
| Oscillospira | ||
| Odoribacter | ||
| Clostridium | ||
| Collinsella | ||
| Bacteroides | ||
| Anaerostipes |
Revision editor(s): Victoria
Experiment 5
Reviewed Marked as Reviewed by KateRasheed on 2025-6-12
Differences from previous experiment shown
Subjects
- Group 0 sample size Number of subjects in the control (unexposed) group
- 31
- Group 1 sample size Number of subjects in the case (exposed) group
- 70
Lab analysis
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- log transformation
- Statistical test
- Sparse Correlations for Compositional data (SparCC)
- Matched on Factors on which subjects have been matched on in a case-control study
- Not specified
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- Not specified
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Reviewed Marked as Reviewed by KateRasheed on 2025-6-12
Source: Figure 3A&B, Supplementary figure 4b
Description: SparCC distance measure to identify correlations of individual taxa with groups.
Abundance in Group 1: increased abundance in Parkinson's disease (PD) group
| NCBI | Quality Control | Links |
|---|---|---|
| Gammaproteobacteria | ||
| Bacteroidaceae | ||
| Oscillospiraceae | ||
| Streptococcaceae | ||
| Veillonellaceae | ||
| Bacteroides | ||
| Streptococcus | ||
| Veillonella |
Revision editor(s): Victoria
Signature 2
Reviewed Marked as Reviewed by KateRasheed on 2025-6-12
Source: Figure 3A&B
Description: SparCC distance measure to identify correlations of individual taxa with groups.
Abundance in Group 1: decreased abundance in Parkinson's disease (PD) group
| NCBI | Quality Control | Links |
|---|---|---|
| Clost. i. s. XIIClost. i. s. XII | ||
| Coprococcus | ||
| Clost. i. s. XIIIClost. i. s. XIII | ||
| Faecalibacterium | ||
| Clostridium |
Revision editor(s): Victoria
Experiment 6
Reviewed Marked as Reviewed by KateRasheed on 2025-6-12
Differences from previous experiment shown
Subjects
- Group 0 sample size Number of subjects in the control (unexposed) group
- 19
- Group 1 sample size Number of subjects in the case (exposed) group
- 28
Lab analysis
Statistical Analysis
- Matched on Factors on which subjects have been matched on in a case-control study
- Matched on: "coffee consumption" 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.coffee consumption, constipation
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- Confounders controlled for: "NMS score" 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.NMS score, Confounders controlled for: "Wexner Constipation Score" 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.Wexner Constipation Score, Confounders controlled for: "coffee consumption" 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.coffee consumption
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Reviewed Marked as Reviewed by KateRasheed on 2025-6-12
Source: Figure 4D
Description: Differences in microbiota after matching for obstipation and coffee consumption with SparCC.
Abundance in Group 1: increased abundance in Parkinson's disease (PD) group
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroides |
Revision editor(s): Victoria
Signature 2
Reviewed Marked as Reviewed by KateRasheed on 2025-6-12
Source: Figure 4D
Description: Differences in microbiota after matching for obstipation and coffee consumption with SparCC.
Abundance in Group 1: decreased abundance in Parkinson's disease (PD) group
| NCBI | Quality Control | Links |
|---|---|---|
| Faecalibacterium |
Revision editor(s): Victoria
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