A Pilot Microbiota Study in Parkinson's Disease Patients versus Control Subjects, and Effects of FTY720 and FTY720-Mitoxy Therapies in Parkinsonian and Multiple System Atrophy Mouse Models
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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
Vidal-Martinez G, Chin B, Camarillo C, Herrera GV, Yang B, Sarosiek I, Perez RG
Journal
Journal of Parkinson's disease
Year
2020
Keywords:
FTY720, FTY720-Mitoxy, Microbiota, Parkinson’s disease, multiple system atrophy, transgenic mouse models
BACKGROUND: Parkinson's disease (PD) and multiple system atrophy (MSA) patients often suffer from gastrointestinal (GI) dysfunction and GI dysbiosis (microbial imbalance). GI dysfunction also occurs in mouse models of PD and MSA. OBJECTIVES: To assess gut dysfunction and dysbiosis in PD subjects as compared to controls, identify potential shared microbial taxa in humans and mouse models of PD and MSA, and to assess the effects of potential therapies on mouse GI microbiota. METHODS: In this human pilot study, GI function was assessed by fecal consistency/frequency measured using the Bristol Stool Form Scale and GI transit time assessed using Sitzmarks pills and abdominal radiology. Human and mouse microbiota were analyzed by extracting fecal genomic DNA followed by 16S rRNA sequencing. RESULTS: In our PD patients genera Akkermansia significantly increased while a trend toward increased Bifidobacterium and decreased Prevotella was observed. Families Bacteroidaceae and Lachnospiraceae and genera Prevotella and Bacteroides were detected in both humans and PD mice, suggesting potential shared biomarkers. In mice treated with the approved multiple sclerosis drug, FTY720, or with our FTY720-Mitoxy-derivative, we saw that FTY720 had little effect while FTY720-Mitoxy increased beneficial Ruminococcus and decreased Rickenellaceae family. CONCLUSION: Akkermansia and Prevotellaceae data reported by others were replicated in our human pilot study suggesting the use of those taxa as potential biomarkers for PD diagnosis. The effect of FTY720-Mitoxy on taxa Rikenellaceae and Ruminococcus and the relevance of S24-7 await further evaluation. It also remains to be determined if mouse microbiota have predictive power for human subjects.
Experiment 1
Needs review
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
- Healthy controls
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Parkinson’s disease
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients diagnosed with Parkinson’s disease (confirmed by a neurologist) between 35 and 95 years of age.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 13
- 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)
- Participants who used antibiotics within 2 weeks prior to the initiation of the study.
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)?
- No
Signature 1
Needs review
Source: Table 1 (Column A)
Description: Relative abundance of gut microbial taxa in pilot studies of human PD.
Abundance in Group 1: increased abundance in Parkinson’s disease
| NCBI | Quality Control | Links |
|---|---|---|
| Akkermansia | ||
| Verrucomicrobiaceae |
Revision editor(s): Flo, Scholastica
Signature 2
Source: Figure 1B
Description: Relative abundance of gut microbial taxa in pilot studies of human PD.
Abundance in Group 1: decreased abundance in Parkinson’s disease
| NCBI | Quality Control | Links |
|---|---|---|
| Prevotella |
Revision editor(s): Flo
Experiment 2
Needs review
Differences from previous experiment shown
Subjects
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Mus musculus
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Wild Type mice
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Parkinsonian mice
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- 10-month old transgenic (Tg) parkinsonian mice that expresses A53T mutant human alpha-synuclein (a-Syn) in neurons
- Group 0 sample size Number of subjects in the control (unexposed) group
- 2
- Group 1 sample size Number of subjects in the case (exposed) group
- 5
- 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
- Statistical test
- Not specified
- Matched on Factors on which subjects have been matched on in a case-control study
- age
Signature 1
Needs review
Source: Table 1 (column B)
Description: Relative abundance of relevant taxa in Wild Type compared to Parkinsonian mice
Abundance in Group 1: increased abundance in Parkinsonian mice
| NCBI | Quality Control | Links |
|---|---|---|
| Bacillota |
Revision editor(s): Flo, Scholastica
Signature 2
Source: Table 1 (column B)
Description: Relative abundance of relevant taxa shared with parkinsonian and multiple system atrophy mouse models.
Abundance in Group 1: decreased abundance in Parkinsonian mice
| NCBI | Quality Control | Links |
|---|---|---|
| Bacillota | ||
| Bacteroidia |
Revision editor(s): Flo
Experiment 3
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Wild Type
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Parkinson’s disease
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- 17 month old transgenic (Tg) mice with Parkinson’s disease that express A53T a-Syn.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 5
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Not specified
Lab analysis
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- Not specified
- Statistical test
- Spearman Correlation
- Matched on Factors on which subjects have been matched on in a case-control study
- Not specified
Signature 1
Source: Table 1 (column C)
Description: Relative abundance of relevant taxa shared with parkinsonian and multiple system atrophy mouse models.
Abundance in Group 1: increased abundance in Parkinson’s disease
| NCBI | Quality Control | Links |
|---|---|---|
| Bacillota | ||
| Bacteroidia |
Revision editor(s): Flo
Signature 2
Source: Table 1 (column C)
Description: Relative abundance of relevant taxa shared with parkinsonian and multiple system atrophy mouse models.
Abundance in Group 1: decreased abundance in Parkinson’s disease
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomycetota | ||
| Pseudomonadota |
Revision editor(s): Flo
Experiment 4
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Multiple system atrophy autonomic failure, Pure,hypotension, orthostatic,MSA,multiple system atrophy,Multiple system atrophy (disorder),multisystem atrophy,orthostatic hypotension syndrome,Shy-Drager Syndrome,Shy-Drager syndrome,Shy-dragger syndrome (formerly),Shy-McGee-Drager syndrome,susceptibility to multiple system atrophy 1,Multiple system atrophy
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Multiple system atrophy
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- 10 - 11 month old transgenic (Tg) mice with with Multiple system atrophy that express CNP-aSyn.
Lab analysis
Statistical Analysis
Signature 1
Source: Table 1 (column D)
Description: Relative abundance of relevant taxa shared with parkinsonian and multiple system atrophy mouse models.
Abundance in Group 1: increased abundance in Multiple system atrophy
| NCBI | Quality Control | Links |
|---|---|---|
| Bacillota | ||
| Bacteroidia |
Revision editor(s): Flo
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