Gut microbiota in Parkinson's disease: Temporal stability and relations to disease progression
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Study information
incomplete
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Aho VTE, Pereira PAB, Voutilainen S, Paulin L, Pekkonen E, Auvinen P, Scheperjans F
Journal
EBioMedicine
Year
2019
Keywords:
Disease progression, Gut microbiota, Gut-brain-axis, Parkinson's disease
BACKGROUND: Several publications have described differences in cross-sectional comparisons of gut microbiota between patients with Parkinson's disease and control subjects, with considerable variability of the reported differentially abundant taxa. The temporal stability of such microbiota alterations and their relationship to disease progression have not been previously studied with a high-throughput sequencing based approach. METHODS: We collected clinical data and stool samples from 64 Parkinson's patients and 64 control subjects twice, on average 2·25 years apart. Disease progression was evaluated based on changes in Unified Parkinson's Disease Rating Scale and Levodopa Equivalent Dose, and microbiota were characterized with 16S rRNA gene amplicon sequencing. FINDINGS: We compared patients to controls, and patients with stable disease to those with faster progression. There were significant differences between microbial communities of patients and controls when corrected for confounders, but not between timepoints. Specific bacterial taxa that differed between patients and controls at both timepoints included several previously reported ones, such as Roseburia, Prevotella and Bifidobacterium. In progression comparisons, differentially abundant taxa were inconsistent across methods and timepoints, but there was some support for a different distribution of enterotypes and a decreased abundance of Prevotella in faster-progressing patients. INTERPRETATION: The previously detected gut microbiota differences between Parkinson's patients and controls persisted after 2 years. While we found some evidence for a connection between microbiota and disease progression, a longer follow-up period is required to confirm these findings.
Statistical test
ANCOM
Experiment 1
Subjects
- 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 at baseline
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Participants with Parkinson's Disease at baseline
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with Parkinson's disease at baseline.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 64
- Group 1 sample size Number of subjects in the case (exposed) group
- 64
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- None.
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
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- .05
- 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
- age, sex
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- body mass index, Confounders controlled for: "Rome III 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.Rome III score, diet
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- unchanged
- Richness Number of species
- unchanged
Signature 1
Source: Figure 4A(using Table 8)
Description: Referencing Table 8 for significances. Baseline. 10 most common bacterial families at each time point. Legend: A. All study subjects by PD status;
Abundance in Group 1: increased abundance in Participants with Parkinson's Disease at baseline
| NCBI | Quality Control | Links |
|---|---|---|
| Alistipes | ||
| Bifidobacteriaceae | ||
| Bifidobacterium |
Revision editor(s): Fcuevas3
Signature 2
Source: Figure 4A(using Table 8)
Description: Referencing Table 8 for significances. Baseline. 10 most common bacterial families at each time point. Legend: A. All study subjects by PD status;
Abundance in Group 1: decreased abundance in Participants with Parkinson's Disease at baseline
| NCBI | Quality Control | Links |
|---|---|---|
| Prevotellaceae |
Revision editor(s): Fcuevas3
Signature 3
Source: Figure 4A(using Table 8)
Description: Referencing Table 8 for significances. Follow-up. 10 most common bacterial families at each time point. Legend: A. All study subjects by PD status;
Abundance in Group 1: increased abundance in Participants with Parkinson's Disease at baseline
| NCBI | Quality Control | Links |
|---|---|---|
| Bifidobacteriaceae | ||
| Bifidobacterium |
Revision editor(s): Fcuevas3
Signature 4
Source: Figure 4A(using Table 8)
Description: Referencing Table 8 for significances. Follow-up. 10 most common bacterial families at each time point. Legend: A. All study subjects by PD status;
Abundance in Group 1: decreased abundance in Participants with Parkinson's Disease at baseline
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroides | ||
| Prevotella | ||
| Prevotellaceae | ||
| Roseburia | ||
| Ruminococcus | ||
| Puniceicoccaceae |
Revision editor(s): Fcuevas3
Experiment 2
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Stable PD patients at follow up
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Progressed PD patients at follow up
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- To classify patients into stable or progressed, we calculated changes in UPDRS I-III score (in the ON state) and LED be- tween baseline and follow-up, divided each value by the number of days between appointments, z-transformed these two variables, and added them up. Based on the distribution of samples on this progression scale, we chose the 3rd quartile as a cut-off, resulting in 41 stable and 15 progressed patients
- Group 0 sample size Number of subjects in the control (unexposed) group
- 41
- Group 1 sample size Number of subjects in the case (exposed) group
- 15
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- None
Lab analysis
Statistical Analysis
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- .1
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- Confounders controlled for: "COMT inhibitor 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.COMT inhibitor use
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- unchanged
- Richness Number of species
- unchanged
Signature 1
Source: Table 9: Follow up.
Description: Summary of differential abundance results contrasting progressed and stable PD patients
Abundance in Group 1: increased abundance in Progressed PD patients at follow up
| NCBI | Quality Control | Links |
|---|---|---|
| Bifidobacterium | ||
| Lachnospiraceae |
Revision editor(s): Fcuevas3
Experiment 3
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy controls at time of follow-up
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Participants with Parkinson's Disease at time of follow-up
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Participants with Parkinson's Disease at time of follow-up
- Group 0 sample size Number of subjects in the control (unexposed) group
- 64
- Group 1 sample size Number of subjects in the case (exposed) group
- 64
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- None.
Lab analysis
Not specified
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- Not specified
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- .05
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- Confounders controlled for: "Rome III 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.Rome III score, body mass index
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- unchanged
- Richness Number of species
- unchanged
Signature 1
Source: Figure 4A(using Table 8)
Description: Referencing Table 8 for significances. Follow-up. 10 most common bacterial families at each time point. Legend: A. All study subjects by PD status;
Abundance in Group 1: increased abundance in Participants with Parkinson's Disease at time of follow-up
| NCBI | Quality Control | Links |
|---|---|---|
| Bifidobacteriaceae | ||
| Bifidobacterium |
Revision editor(s): Fcuevas3
Signature 2
Source: Figure 4A(using Table 8)
Description: Referencing Table 8 for significances. Follow-up. 10 most common bacterial families at each time point. Legend: A. All study subjects by PD status;
Abundance in Group 1: decreased abundance in Participants with Parkinson's Disease at time of follow-up
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroides | ||
| Prevotella | ||
| Prevotellaceae | ||
| Roseburia | ||
| Ruminococcus | ||
| unclassified Puniceicoccaceae |
Revision editor(s): Fcuevas3
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