Fecal microbiome alterations in treatment-naive de novo Parkinson's disease
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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
Boertien JM, Murtomäki K, Pereira PAB, van der Zee S, Mertsalmi TH, Levo R, Nojonen T, Mäkinen E, Jaakkola E, Laine P, Paulin L, Pekkonen E, Kaasinen V, Auvinen P, Scheperjans F, van Laar T
Journal
NPJ Parkinson's disease
Year
2022
Gut microbiota alterations in Parkinson's disease (PD) have been found in several studies and are suggested to contribute to the pathogenesis of PD. However, previous results could not be adequately adjusted for a potential confounding effect of PD medication and disease duration, as almost all PD participants were already using dopaminergic medication and were included several years after diagnosis. Here, the gut microbiome composition of treatment-naive de novo PD subjects was assessed compared to healthy controls (HC) in two large independent case-control cohorts (n = 136 and 56 PD, n = 85 and 87 HC), using 16S-sequencing of fecal samples. Relevant variables such as technical batches, diet and constipation were assessed for their potential effects. Overall gut microbiome composition differed between PD and HC in both cohorts, suggesting gut microbiome alterations are already present in de novo PD subjects at the time of diagnosis, without the possible confounding effect of dopaminergic medication. Although no differentially abundant taxon could be replicated in both cohorts, multiple short chain fatty acids (SCFA) producing taxa were decreased in PD in both cohorts. In particular, several taxa belonging to the family Lachnospiraceae were decreased in abundance. Fewer taxonomic differences were found compared to previous studies, indicating smaller effect sizes in de novo PD.
Experiment 1
Reviewed Marked as Reviewed by Atrayees on 2023-7-7
Curated date: 2023/06/03
Curator: Fcuevas3
Revision editor(s): LGeistlinger, Fcuevas3, Atrayees, Victoria
Subjects
- Location of subjects
- Netherlands
- 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 subjects
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Dutch(NL) Cohort: Parkinson's disease diagnosis by a movement disorder specialist according to the Movement Disorders Society (MDS) clinical diagnostic criteria1, confirmed by a dopaminergic deficit quantified by FDOPA-PET or one-year follow-up if no FDOPA-PET was performed.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 85
- Group 1 sample size Number of subjects in the case (exposed) group
- 136
- 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
- V4-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
- Statistical test
- ANCOM
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.1
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, body mass index, Confounders controlled for: "stool consistency" 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.stool consistency, Confounders controlled for: "stool frequency" 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.stool frequency
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- increased
- Richness Number of species
- increased
Signature 1
Reviewed Marked as Reviewed by Atrayees on 2023-7-7
Source: Table 3. Differentially abundant taxa between PD and HC in NL cohort..
Description: Differentially abundant taxa between PD and HC detected using ANCOM.
- (A negative change indicates lower abundance in PD compared to HC)
Abundance in Group 1: increased abundance in Parkinson's Disease subjects
| NCBI | Quality Control | Links |
|---|---|---|
| Rikenellaceae |
Signature 2
Reviewed Marked as Reviewed by Atrayees on 2023-7-7
Source: Table 3.
Description: Differentially abundant taxa between PD and HC detected using ANCOM.
Abundance in Group 1: decreased abundance in Parkinson's Disease subjects
| NCBI | Quality Control | Links |
|---|---|---|
| Lachnoclostridium | ||
| Lachnospiraceae | ||
| Roseburia | ||
| Veillonellaceae |
Experiment 2
Reviewed Marked as Reviewed by Atrayees on 2023-7-7
Differences from previous experiment shown
Subjects
- Location of subjects
- Finland
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Finnish(FIN) Cohort: Parkinson's disease diagnosis by a movement disorder specialist according to the MDS clinical diagnostic criteria1, confirmed by a dopaminergic deficit quantified by [I-123]FP-CIT SPECT. [I-123]FP-CIT SPECT were analyzed with BRASS software (Hermes Medical Solutions AB, Stockholm, Sweden), in which a dopaminergic deficit was defined as more than two standard deviations below the reference mean in any of the six analyzed regions.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 87
- Group 1 sample size Number of subjects in the case (exposed) group
- 56
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Recent antibiotics usage in the previous month.
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- Confounders controlled for: "stool consistency" 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.stool consistency, Confounders controlled for: "number of reads" 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.number of reads
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of 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 2
Reviewed Marked as Reviewed by Atrayees on 2023-7-7
Source: Table 3.
Description: Differentially abundant taxa between PD and HC detected using ANCOM
Abundance in Group 1: decreased abundance in Parkinson's Disease subjects
| NCBI | Quality Control | Links |
|---|---|---|
| Roseburia inulinivorans | ||
| Lachnoclostridium edouardi | ||
| Lachnospiraceae | ||
| Colidextribacter | ||
| Roseburia |
Experiment 3
Reviewed Marked as Reviewed by Atrayees on 2023-7-7
Differences from previous experiment shown
Subjects
- Location of subjects
- Netherlands
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Dutch(NL) Cohort: Parkinson's disease diagnosis by a movement disorder specialist according to the Movement Disorders Society (MDS) clinical diagnostic criteria1, confirmed by a dopaminergic deficit quantified by FDOPA-PET or one-year follow-up if no FDOPA-PET was performed.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 85
- Group 1 sample size Number of subjects in the case (exposed) group
- 136
Lab analysis
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- raw counts
- Statistical test
- DESeq2
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, body mass index, Confounders controlled for: "stool consistency" 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.stool consistency, Confounders controlled for: "stool frequency" 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.stool frequency
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- increased
- Richness Number of species
- increased
Experiment 4
Reviewed Marked as Reviewed by Atrayees on 2023-7-7
Differences from previous experiment shown
Subjects
- Location of subjects
- Finland
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Finnish(FIN) Cohort: Parkinson's disease diagnosis by a movement disorder specialist according to the MDS clinical diagnostic criteria1, confirmed by a dopaminergic deficit quantified by [I-123]FP-CIT SPECT. [I-123]FP-CIT SPECT were analyzed with BRASS software (Hermes Medical Solutions AB, Stockholm, Sweden), in which a dopaminergic deficit was defined as more than two standard deviations below the reference mean in any of the six analyzed regions.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 87
- Group 1 sample size Number of subjects in the case (exposed) group
- 56
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- Confounders controlled for: "stool consistency" 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.stool consistency, Confounders controlled for: "number of reads" 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.number of reads
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of 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 2
Reviewed Marked as Reviewed by Atrayees on 2023-7-7
Source: Table 3.
Description: Differentially abundant taxa between PD and HC detected using DESeq2.
Abundance in Group 1: decreased abundance in Parkinson's Disease subjects
| NCBI | Quality Control | Links |
|---|---|---|
| Lachnospiraceae | ||
| Butyricicoccus | ||
| Acholeplasmataceae |
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