Parkinson's disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions
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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 Uniform resource identifier for web resources.
Authors
Baldini F, Hertel J, Sandt E, Thinnes CC, Neuberger-Castillo L, Pavelka L, Betsou F, Krüger R, Thiele I
Journal
BMC biology
Year
2020
BACKGROUND: Parkinson's disease (PD) is a systemic disease clinically defined by the degeneration of dopaminergic neurons in the brain. While alterations in the gut microbiome composition have been reported in PD, their functional consequences remain unclear. Herein, we addressed this question by an analysis of stool samples from the Luxembourg Parkinson's Study (n = 147 typical PD cases, n = 162 controls). RESULTS: All individuals underwent detailed clinical assessment, including neurological examinations and neuropsychological tests followed by self-reporting questionnaires. Stool samples from these individuals were first analysed by 16S rRNA gene sequencing. Second, we predicted the potential secretion for 129 microbial metabolites through personalised metabolic modelling using the microbiome data and genome-scale metabolic reconstructions of human gut microbes. Our key results include the following. Eight genera and seven species changed significantly in their relative abundances between PD patients and healthy controls. PD-associated microbial patterns statistically depended on sex, age, BMI, and constipation. Particularly, the relative abundances of Bilophila and Paraprevotella were significantly associated with the Hoehn and Yahr staging after controlling for the disease duration. Furthermore, personalised metabolic modelling of the gut microbiomes revealed PD-associated metabolic patterns in the predicted secretion potential of nine microbial metabolites in PD, including increased methionine and cysteinylglycine. The predicted microbial pantothenic acid production potential was linked to the presence of specific non-motor symptoms. CONCLUSION: Our results suggest that PD-associated alterations of the gut microbiome can translate into substantial functional differences affecting host metabolism and disease phenotype.
Experiment 1
Subjects
- Location of subjects
- Luxembourg
- 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
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Participants with typical PD
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- PD patients were defined as typical PD, according to the inclusion criteria by the United Kingdom Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 162
- Group 1 sample size Number of subjects in the case (exposed) group
- 147
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Excluded control persons who took dopaminergic medications (n = 5; intake for a different than anti-PD indication) and individuals who reported to have taken antibiotics in the last 6 months (controls: n = 20, PD: n = 13).
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
- Statistical test
- Linear Regression
- 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, Confounders controlled for: "gender" 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.gender, Confounders controlled for: "BMI" 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.BMI
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Richness Number of species
- increased
Signature 1
Source: Figure 2.
Description: Boxplots of seven significantly changed species in PD vs. controls (FDR < 0.05).
Abundance in Group 1: increased abundance in Participants with typical PD
| NCBI | Links |
|---|---|
| Akkermansia muciniphila | |
| Anaerotruncus colihominis | |
| Christensenella minuta ⚠ | |
| Ruminococcus bromii | |
| [Ruminococcus] torques |
Revision editor(s): Fcuevas3
Signature 2
Source: Figure 2.
Description: Boxplots of seven significantly changed species in PD vs. controls (FDR < 0.05).
Abundance in Group 1: decreased abundance in Participants with typical PD
| NCBI | Links |
|---|---|
| Turicibacter sanguinis | |
| Roseburia intestinalis |
Revision editor(s): Fcuevas3
Experiment 2
Subjects
- Location of subjects
- Luxembourg
- 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
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Participants with typical PD
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- PD patients were defined as typical PD, according to the inclusion criteria by the United Kingdom Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 162
- Group 1 sample size Number of subjects in the case (exposed) group
- 147
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Excluded control persons who took dopaminergic medications (n = 5; intake for a different than anti-PD indication) and individuals who reported to have taken antibiotics in the last 6 months (controls: n = 20, PD: n = 13).
Lab analysis
- Sequencing type
- 16S
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Statistical test
- Linear Regression
- 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, Confounders controlled for: "gender" 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.gender, Confounders controlled for: "BMI" 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.BMI
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Richness Number of species
- increased
Signature 1
Source: Figure 3.
Description: Boxplots of eight significantly changed genera in PD vs. controls (FDR < 0.05).
Abundance in Group 1: increased abundance in Participants with typical PD
| NCBI | Links |
|---|---|
| Christensenella ⚠ | |
| Anaerotruncus | |
| Lactobacillus | |
| Bilophila | |
| Akkermansia | |
| Streptococcus |
Revision editor(s): Fcuevas3
Signature 2
Source: Figure 3.
Description: Boxplots of eight significantly changed genera in PD vs. controls (FDR < 0.05)
Abundance in Group 1: decreased abundance in Participants with typical PD
| NCBI | Links |
|---|---|
| Turicibacter |
Revision editor(s): Fcuevas3
Experiment 3
Subjects
- Location of subjects
- Luxembourg
- 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
- Female patients with PD
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Male patients with PD
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Female/male patients with PD according to United Kingdom Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 57
- Group 1 sample size Number of subjects in the case (exposed) group
- 105
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Excluded control persons who took dopaminergic medications (n = 5; intake for a different than anti-PD indication) and individuals who reported to have taken antibiotics in the last 6 months (controls: n = 20, PD: n = 13).
Lab analysis
- Sequencing type
- 16S
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Statistical test
- Linear Regression
- 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, Confounders controlled for: "gender" 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.gender, Confounders controlled for: "BMI" 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.BMI
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Richness Number of species
- increased
Signature 1
Source: Figure 4
Description: Genus alterations in PDs in the context of basic covariates and clinical variables.
Abundance in Group 1: increased abundance in Male patients with PD
| NCBI | Links |
|---|---|
| Paraprevotella |
Revision editor(s): Fcuevas3
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