The Gut Microbiome in Parkinson's Disease: A Longitudinal Study of the Impacts on Disease Progression and the Use of Device-Assisted Therapies
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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.
Authors
Lubomski M, Xu X, Holmes AJ, Muller S, Yang JYH, Davis RL, Sue CM
Journal
Frontiers in aging neuroscience
Year
2022
Keywords:
Parkinson’s disease, deep brain stimulation, device-assisted therapies, gastrointestinal microbiome, gut microbiota, levodopa-carbidopa intestinal gel, longitudinal, progression
BACKGROUND: Altered gut microbiome (GM) composition has been established in Parkinson's disease (PD). However, few studies have longitudinally investigated the GM in PD, or the impact of device-assisted therapies. OBJECTIVES: To investigate the temporal stability of GM profiles from PD patients on standard therapies and those initiating device-assisted therapies (DAT) and define multivariate models of disease and progression. METHODS: We evaluated validated clinical questionnaires and stool samples from 74 PD patients and 74 household controls (HCs) at 0, 6, and 12 months. Faster or slower disease progression was defined from levodopa equivalence dose and motor severity measures. 19 PD patients initiating Deep Brain Stimulation or Levodopa-Carbidopa Intestinal Gel were separately evaluated at 0, 6, and 12 months post-therapy initiation. RESULTS: Persistent underrepresentation of short-chain fatty-acid-producing bacteria, Butyricicoccus, Fusicatenibacter, Lachnospiraceae ND3007 group, and Erysipelotrichaceae UCG-003, were apparent in PD patients relative to controls. A sustained effect of DAT initiation on GM associations with PD was not observed. PD progression analysis indicated that the genus Barnesiella was underrepresented in faster progressing PD patients at t = 0 and t = 12 months. Two-stage predictive modeling, integrating microbiota abundances and nutritional profiles, improved predictive capacity (change in Area Under the Curve from 0.58 to 0.64) when assessed at Amplicon Sequence Variant taxonomic resolution. CONCLUSION: We present longitudinal GM studies in PD patients, showing persistently altered GM profiles suggestive of a reduced butyrogenic production potential. DATs exerted variable GM influences across the short and longer-term. We found that specific GM profiles combined with dietary factors improved prediction of disease progression in PD patients.
Experiment 1
Subjects
- Location of subjects
- Australia
- 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
- Blood , Feces Portion of blood,Vertebrate blood,Whole blood,Blood,blood,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
- Household Control
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Parkinson's diease (PD) patients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- PD patients on standard therapies
- Group 0 sample size Number of subjects in the control (unexposed) group
- 74
- Group 1 sample size Number of subjects in the case (exposed) group
- 74
- 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).
- centered log-ratio
- 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
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, diet, sex, constipation
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Source: Result, Figure 2
Description: Differentially abundant taxa between the PD and HC groups across the three timepoints; bacteria that produce short chain fatty-acids in PD patients compared to healthy controls
Abundance in Group 1: decreased abundance in Parkinson's diease (PD) patients
| NCBI | Quality Control | Links |
|---|---|---|
| Butyricicoccus | ||
| Fusicatenibacter | ||
| Lachnospiraceae | ||
| erysipelotrichaceae UCG-003erysipelotrichaceae UCG-003 |
Revision editor(s): Bolanle
Experiment 2
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Patients with Slow progressing Parkinson's disease
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Patients with Faster progressing Parkinson's disease
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with faster progressing parkinson's disease over a 12 month period
- Group 0 sample size Number of subjects in the control (unexposed) group
- 40
- Group 1 sample size Number of subjects in the case (exposed) group
- 34
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- All participants had not received antibiotics supplements for at least 1 month prior sample collection
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, sex
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Source: Figure 4
Description: Differential abundance of taxa between faster progressing and slower progressing PD patients within 12 months, specifically at two-time intervals(t=0, t=12)
Abundance in Group 1: decreased abundance in Patients with Faster progressing Parkinson's disease
| NCBI | Quality Control | Links |
|---|---|---|
| Barnesiellaceae |
Revision editor(s): Bolanle
Experiment 3
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Pre DAT(device assisted therapy)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- DBS(deep brain stimulation)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- initiation of DBS therapy on parkinson's disease patients at 0 month
- Group 0 sample size Number of subjects in the control (unexposed) group
- 74
- Group 1 sample size Number of subjects in the case (exposed) group
- 9
- 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
Statistical Analysis
- Statistical test
- ANOVA
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.01
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, diet, sex, constipation
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Experiment 4
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Pre DAT(device assisted therapy) PD patients
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- LCIG(Levodopa-Carbidopa Intestinal Gel)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- initiation of LCIG therapy on parkinson's disease patients at 0 month
- Group 1 sample size Number of subjects in the case (exposed) group
- 10
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Experiment 5
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Household Control
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Parkinson's diease patients at 6 months
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- PD patients on standard therapies at 6months
- Group 1 sample size Number of subjects in the case (exposed) group
- 74
Lab analysis
Statistical Analysis
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, body mass index, sex
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Source: Figure 2 text
Description: There was statistically significant underrepresentation of the bacterial signatures in the gut microbiota of PD patients at 6months time point compared to healthy controls
Abundance in Group 1: decreased abundance in Parkinson's diease patients at 6 months
Revision editor(s): Bolanle
Signature 2
Source: Figure 7 text
Description: There was statistically significant overrepresentation of the bacterial signatures in the gut microbiota of PD patients at 6months time point compared to healthy controls
Abundance in Group 1: increased abundance in Parkinson's diease patients at 6 months
| NCBI | Quality Control | Links |
|---|---|---|
| Enterobacteriaceae | ||
| unclassified Lactobacillaceae |
Revision editor(s): Bolanle
Experiment 6
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Parkinson's diease patients at 12 months
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Parkinson's disease patients samples collected at 12months
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, diet, sex, constipation
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Source: Figure 2 text
Description: There was statistically significant overrepresentation of the bacterial signatures in the gut microbiota of PD patients at 12months time point compared to healthy control
Abundance in Group 1: decreased abundance in Parkinson's diease patients at 12 months
| NCBI | Quality Control | Links |
|---|---|---|
| Anaerostipes | ||
| Butyricicoccaceae |
Revision editor(s): Bolanle
Signature 3
Source: Figure 2 text
Description: There was statistically significant overrepresentation of the bacterial signatures in the gut microbiota of PD patients at 12months time point compared to healthy control
Abundance in Group 1: increased abundance in Parkinson's diease patients at 12 months
| NCBI | Quality Control | Links |
|---|---|---|
| unclassified Lactobacillaceae |
Revision editor(s): Bolanle
Experiment 7
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Pre DAT(device assisted therapy)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- DBS(deep brain stimulation)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- initiation of DBS therapy on parkinson's disease patients at 6 month
- Group 1 sample size Number of subjects in the case (exposed) group
- 9
Lab analysis
Statistical Analysis
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.01
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Source: figure 7
Description: the most differentially abbundant taxa after the initiation of DS therapy at 0-6months timepoint included overrepresentation of the geus level
Abundance in Group 1: increased abundance in DBS(deep brain stimulation)
| NCBI | Quality Control | Links |
|---|---|---|
| Prevotella |
Revision editor(s): Bolanle
Experiment 8
Differences from previous experiment shown
Subjects
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- initiation of DBS therapy on parkinson's disease patients at 12 month
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Source: Figure 7
Description: DBS therapy patients showed overrepresentation of these taxa (t=12moths)
Abundance in Group 1: increased abundance in DBS(deep brain stimulation)
| NCBI | Quality Control | Links |
|---|---|---|
| Bacillaceae | ||
| Bacillus | ||
| Citrobacter | ||
| Faecalicoccus | ||
| Methanobacteriaceae | ||
| Methanobrevibacter | ||
| Morganella | ||
| Prevotella | ||
| Spirochaetaceae | ||
| Treponema | ||
| Veillonella |
Revision editor(s): Bolanle
Signature 2
Source: Figure 7
Description: DBS therapy patients showed uderrepresentation of these taxa after 12 months initiation
Abundance in Group 1: decreased abundance in DBS(deep brain stimulation)
| NCBI | Quality Control | Links |
|---|---|---|
| Acetanaerobacterium | ||
| Anaerotruncus | ||
| Flavonifractor | ||
| Hespellia | ||
| Howardella |
Revision editor(s): Bolanle
Experiment 9
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Pre DAT(device assisted therapy) PD patients
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- LCIG(Levodopa-Carbidopa Intestinal Gel)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- initiation of LCIG therapy on parkinson's disease patients at 6 month
- Group 1 sample size Number of subjects in the case (exposed) group
- 10
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Source: Figure 7
Description: Gut microbiome compositional differences in response to the initiation and continuation Levodopa-Carbidopa Intestinal gel (LCIG) therapies at 6months
Abundance in Group 1: increased abundance in LCIG(Levodopa-Carbidopa Intestinal Gel)
| NCBI | Quality Control | Links |
|---|---|---|
| Prevotellaceae | ||
| Roseburia |
Revision editor(s): Bolanle
Signature 2
Source: Figure 7
Description: Gut microbiome compositional differences in response to the initiation and continuation Levodopa-Carbidopa Intestinal gel (LCIG) therapies at 6months
Abundance in Group 1: decreased abundance in LCIG(Levodopa-Carbidopa Intestinal Gel)
| NCBI | Quality Control | Links |
|---|---|---|
| Acetanaerobacterium | ||
| Eggerthella | ||
| Gordonibacter | ||
| Hespellia | ||
| Holdemania |
Revision editor(s): Bolanle
Experiment 10
Differences from previous experiment shown
Subjects
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- initiation of LCIG therapy on parkinson's disease patients at 12 month
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Source: Figure 7
Description: Gut microbiome compositional differences in response to the initiation and continuation Levodopa-Carbidopa Intestinal gel (LCIG) therapies at 12months
Abundance in Group 1: increased abundance in LCIG(Levodopa-Carbidopa Intestinal Gel)
| NCBI | Quality Control | Links |
|---|---|---|
| Bacillus | ||
| Prevotella |
Revision editor(s): Bolanle
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