The Parkinson's disease drug entacapone disrupts gut microbiome homoeostasis via iron sequestration
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Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
Experiment 1
Subjects
- Location of subjects
- Austria
- United Kingdom
- 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
- Response to drug drug resistance,drug susceptibility/resistance,Response to drug,response to drug
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Loxapine Succinate High (LOX-High), Loxapine Succinate Low(LOX-Low) and Entacapone Low(ENT-Low) after 24hours of incubation
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Entacapone High Concentration(ENT-High) after 24 hrs of incubation
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Entacapone High Concentration(ENT-High) after 24hrs of incubation, refers to the drug concentration given to the six healthy adult individuals after twenty-four hours of incubation. Entacapone is a catechol-O-methyltransferase (COMT) inhibitor that acts by preventing the degradation of levodopa. It is the main drug used in the treatment of Parkinson’s disease. High concentration was based on estimated colon concentration and was included to better reflect the exposure of gut microbes to drugs in the large intestine.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 9
- Group 1 sample size Number of subjects in the case (exposed) group
- 3
- 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
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- 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).
- raw counts
- Statistical test
- DESeq2
- 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
Signature 1
Source: Supplementary Table 5
Description: Differential abundance of taxa between the drug-amendment experiments(ENT-High, ENT-Low, LOX-High and LOX-Low) after 24hrs of incubation.
Abundance in Group 1: increased abundance in Entacapone High Concentration(ENT-High) after 24 hrs of incubation
Revision editor(s): KateRasheed
Signature 2
Source: Supplementary Table 5
Description: Differential abundance of taxa between the drug-amendment experiments(ENT-High, ENT-Low, LOX-High and LOX-Low) after 24hrs of incubation.
Abundance in Group 1: decreased abundance in Entacapone High Concentration(ENT-High) after 24 hrs of incubation
Revision editor(s): KateRasheed
Experiment 2
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Loxapine Succinate High (LOX-High), Entacapone Concentration(ENT-High) and Entacapone Low(ENT-Low) after 24hours of incubation
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Loxapine Succinate Low Concentration(LOX-Low) after 24 hrs of incubation
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Loxapine Succinate Low Concentration(LOX-Low) after 24 hrs of incubation refers to the drug concentration given to the six healthy adult individuals after twenty-four hours of incubation.
Lab analysis
Statistical Analysis
Signature 1
Source: Supplementary Table 5
Description: Differential abundance of taxa between the drug-amendment experiments(ENT-High, ENT-Low, LOX-High and LOX-Low) after 24hrs of incubation.
Abundance in Group 1: increased abundance in Loxapine Succinate Low Concentration(LOX-Low) after 24 hrs of incubation
Revision editor(s): KateRasheed
Signature 2
Source: Supplementary Table 5
Description: Differential abundance of taxa between the drug-amendment experiments(ENT-High, ENT-Low, LOX-High and LOX-Low) after 24hrs of incubation.
Abundance in Group 1: decreased abundance in Loxapine Succinate Low Concentration(LOX-Low) after 24 hrs of incubation
Revision editor(s): KateRasheed
Experiment 3
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Loxapine Succinate High (LOX-High), Loxapine Succinate Low(LOX-Low) and Entacapone High(ENT-High) after 24hours of incubation
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Entacapone Low Concentration(ENT-Low) after 24 hrs of incubation
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Entacapone Low Concentration(ENT-Low) after 24 hrs of incubation refers to the drug concentration given to the six healthy adult individuals after twenty-four hours of incubation. Entacapone is a catechol-O-methyltransferase (COMT) inhibitor that acts by preventing the degradation of levodopa. It is the main drug used in the treatment of Parkinson’s disease. The low drug concentration was previously used in a screening aimed at determining drug effects on pure culture isolates.
Lab analysis
Statistical Analysis
Signature 1
Source: Supplementary Table 5
Description: Differential abundance of taxa between the drug-amendment experiments(ENT-High, ENT-Low, LOX-High and LOX-Low) after 24hrs of incubation.
Abundance in Group 1: increased abundance in Entacapone Low Concentration(ENT-Low) after 24 hrs of incubation
Revision editor(s): KateRasheed
Signature 2
Source: Supplementary Table 5
Description: Differential abundance of taxa between the drug-amendment experiments(ENT-High, ENT-Low, LOX-High and LOX-Low) after 24hrs of incubation.
Abundance in Group 1: decreased abundance in Entacapone Low Concentration(ENT-Low) after 24 hrs of incubation
| NCBI | Quality Control | Links |
|---|---|---|
| Subdoligranulum | ||
| Oscillospiraceae UCG-002Oscillospiraceae UCG-002 | ||
| uncultured Oscillospiraceae bacterium | ||
| uncultured_unclassifieduncultured_unclassified |
Revision editor(s): KateRasheed
Experiment 4
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Loxapine Succinate Low(LOX-Low), Entacapone High(ENT-High) and Entacapone Low(ENT-Low) after 24hours of incubation
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Loxapine Succinate High Concentration(LOX-High) after 24 hrs of incubation
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Loxapine Succinate High Concentration(LOX-High) after 24 hrs of incubation, refers to the drug concentration given to the six healthy adult individuals after twenty-four hours of incubation. Loxapine succinate is a tricyclic antipsychotic medication primarily used in the treatment of schizophrenia. High concentration was based on estimated colon concentration and was included to better reflect the exposure of gut microbes to drugs in the large intestine.
Lab analysis
Statistical Analysis
Signature 1
Source: Supplementary Table 5
Description: Differential abundance of taxa between the drug-amendment experiments(ENT-High, ENT-Low, LOX-High and LOX-Low) after 24hrs of incubation.
Abundance in Group 1: increased abundance in Loxapine Succinate High Concentration(LOX-High) after 24 hrs of incubation
Revision editor(s): KateRasheed
Signature 2
Source: Supplementary Table 5
Description: Differential abundance of taxa between the drug-amendment experiments(ENT-High, ENT-Low, LOX-High and LOX-Low) after 24hrs of incubation.
Abundance in Group 1: decreased abundance in Loxapine Succinate High Concentration(LOX-High) after 24 hrs of incubation
Revision editor(s): KateRasheed
Experiment 5
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Loxapine Succinate High (LOX-High) and Entacapone Low(ENT-Low) after 6hours of incubation
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Loxapine Succinate Low Concentration(LOX-Low) after 6hrs of incubation
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Loxapine Succinate Low Concentration(LOX-Low) after 6hrs of incubation refers to the drug concentration given to the six healthy adult individuals after six hours of incubation. Loxapine succinate is a tricyclic antipsychotic medication primarily used in the treatment of schizophrenia. The low drug concentration was previously used in a screening aimed at determining drug effects on pure culture isolates.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 6
Lab analysis
Statistical Analysis
Signature 1
Source: Supplementary Table 5
Description: Differential abundance of taxa between the drug-amendment experiments(ENT-Low, LOX-High and LOX-Low) after 6hrs of incubation.
Abundance in Group 1: increased abundance in Loxapine Succinate Low Concentration(LOX-Low) after 6hrs of incubation
| NCBI | Quality Control | Links |
|---|---|---|
| Streptococcus |
Revision editor(s): KateRasheed
Signature 2
Source: Supplementary Table 5
Description: Differential abundance of taxa between the drug-amendment experiments(ENT-Low, LOX-High and LOX-Low) after 6hrs of incubation.
Abundance in Group 1: decreased abundance in Loxapine Succinate Low Concentration(LOX-Low) after 6hrs of incubation
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroides |
Revision editor(s): KateRasheed
Experiment 6
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Loxapine Succinate High (LOX-High) and Loxapine Succinate Low(LOX-Low) after 6hours of incubation
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Entacapone Low Concentration(ENT-Low) after 6hrs of incubation
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Entacapone Low Concentration(ENT-Low) after 6hrs of incubation refers to the drug concentration given to the six healthy adult individuals after six hours of incubation. Entacapone is a catechol-O-methyltransferase (COMT) inhibitor that acts by preventing the degradation of levodopa. It is the main drug used in the treatment of Parkinson’s disease. The low drug concentration was previously used in a screening aimed at determining drug effects on pure culture isolates.
Lab analysis
Statistical Analysis
Signature 1
Source: Supplementary Table 5
Description: Differential abundance of taxa between the drug-amendment experiments(ENT-Low, LOX-High and LOX-Low) after 6hrs of incubation.
Abundance in Group 1: increased abundance in Entacapone Low Concentration(ENT-Low) after 6hrs of incubation
| NCBI | Quality Control | Links |
|---|---|---|
| Streptococcus |
Revision editor(s): KateRasheed
Experiment 7
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Loxapine Succinate Low(LOX-Low) and Entacapone Low(ENT-Low) after 6hours of incubation
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Loxapine Succinate High Concentration(LOX-High) after 6hrs of incubation
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Loxapine Succinate High Concentration(LOX-High) after 6hrs of incubation refers to the drug concentration given to the six healthy adult individuals after six hours of incubation. Loxapine succinate is a tricyclic antipsychotic medication primarily used in the treatment of schizophrenia. High concentration was based on estimated colon concentration and was included to better reflect the exposure of gut microbes to drugs in the large intestine.
Lab analysis
Statistical Analysis
Signature 1
Source: Supplementary Table 5
Description: Differential abundance of taxa between the drug-amendment experiments(ENT-Low, LOX-High and LOX-Low) after 6hrs of incubation.
Abundance in Group 1: increased abundance in Loxapine Succinate High Concentration(LOX-High) after 6hrs of incubation
| NCBI | Quality Control | Links |
|---|---|---|
| Streptococcus sp. |
Revision editor(s): KateRasheed
Signature 2
Source: Supplementary Table 5
Description: Differential abundance of taxa between the drug-amendment experiments(ENT-Low, LOX-High and LOX-Low) after 6hrs of incubation.
Abundance in Group 1: decreased abundance in Loxapine Succinate High Concentration(LOX-High) after 6hrs of incubation
| NCBI | Quality Control | Links |
|---|---|---|
| Clostridium sp. | ||
| Bacteroides |
Revision editor(s): KateRasheed
Experiment 8
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- No drug - Dimethyl sulfoxide only (DMSO only)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Entacapone High Concentration(ENT-High) after 24 hrs of incubation - Donor 1
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Entacapone High Concentration(ENT-High) after 24 hrs of incubation refers to the drug concentration given to donor 1 after twenty-four hours of incubation. Entacapone is a catechol-O-methyltransferase (COMT) inhibitor that acts by preventing the degradation of levodopa. It is the main drug used in the treatment of Parkinson’s disease. High concentration was based on estimated colon concentration and was included to better reflect the exposure of gut microbes to drugs in the large intestine.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 3
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- decreased
- Richness Number of species
- decreased
Signature 1
Source: Supplementary Table 6
Description: Differential abundance of taxa between No drug and ENT-High in Donor 1 after 24hrs of incubation.
Abundance in Group 1: increased abundance in Entacapone High Concentration(ENT-High) after 24 hrs of incubation - Donor 1
Revision editor(s): KateRasheed
Signature 2
Source: Supplementary Table 6
Description: Differential abundance of taxa between No drug and ENT-High in Donor 1 after 24hrs of incubation.
Abundance in Group 1: decreased abundance in Entacapone High Concentration(ENT-High) after 24 hrs of incubation - Donor 1
Revision editor(s): KateRasheed
Experiment 9
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Entacapone High Concentration(ENT-High) after 24 hrs of incubation - Donor 2
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Entacapone High Concentration(ENT-High) after 24 hrs of incubation refers to the drug concentration given to donor 2 after twenty-four hours of incubation. Entacapone is a catechol-O-methyltransferase (COMT) inhibitor that acts by preventing the degradation of levodopa. It is the main drug used in the treatment of Parkinson’s disease. High concentration was based on estimated colon concentration and was included to better reflect the exposure of gut microbes to drugs in the large intestine.
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- decreased
- Richness Number of species
- decreased
Signature 1
Source: Supplementary Table 6
Description: Differential abundance of taxa between No drug and ENT-High in Donor 2 after 24hrs of incubation.
Abundance in Group 1: increased abundance in Entacapone High Concentration(ENT-High) after 24 hrs of incubation - Donor 2
Revision editor(s): KateRasheed
Signature 2
Source: Supplementary Table 6
Description: Differential abundance of taxa between No drug and ENT-High in Donor 2 after 24hrs of incubation.
Abundance in Group 1: decreased abundance in Entacapone High Concentration(ENT-High) after 24 hrs of incubation - Donor 2
Revision editor(s): KateRasheed
Experiment 10
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Entacapone High Concentration(ENT-High) after 24 hrs of incubation - Donor 3
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Entacapone High Concentration(ENT-High) after 24 hrs of incubation, refers to the drug concentration given to donor 3 after twenty-four hours of incubation. Entacapone is a catechol-O-methyltransferase (COMT) inhibitor that acts by preventing the degradation of levodopa. It is the main drug used in the treatment of Parkinson’s disease. High concentration was based on estimated colon concentration and was included to better reflect the exposure of gut microbes to drugs in the large intestine.
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- decreased
- Richness Number of species
- decreased
Signature 1
Source: Supplementary Table 6
Description: Differential abundance of taxa between No drug and ENT-High in Donor 3 after 24hrs of incubation.
Abundance in Group 1: increased abundance in Entacapone High Concentration(ENT-High) after 24 hrs of incubation - Donor 3
Revision editor(s): KateRasheed
Signature 2
Source: Supplementary Table 6
Description: Differential abundance of taxa between No drug and ENT-High in Donor 3 after 24hrs of incubation.
Abundance in Group 1: decreased abundance in Entacapone High Concentration(ENT-High) after 24 hrs of incubation - Donor 3
Revision editor(s): KateRasheed
