Altered gut microbiota and inflammatory cytokine responses in patients with 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 Uniform resource identifier for web resources.
Authors
Lin CH, Chen CC, Chiang HL, Liou JM, Chang CM, Lu TP, Chuang EY, Tai YC, Cheng C, Lin HY, Wu MS
Journal
Journal of neuroinflammation
Year
2019
OBJECTIVE: Emerging evidence suggests that gut microbiome composition alterations affect neurodegeneration through neuroinflammation in the pathogenesis of Parkinson's disease (PD). Here, we evaluate gut microbiota alterations and host cytokine responses in a population of Taiwanese patients with PD. METHODS: Fecal microbiota communities from 80 patients with PD and 77 age and gender-matched controls were assessed by sequencing the V3-V4 region of the 16S ribosomal RNA gene. Diet and comorbidities were controlled in the analyses. Plasma concentrations of IL-1β, IL-2, IL-4, IL-6, IL-13, IL-18, GM-CSF, IFNγ, and TNFα were measured by a multiplex immunoassay and relationships between microbiota, clinical characteristics, and cytokine levels were analyzed in the PD group. We further examined the cytokine changes associated with the altered gut microbiota seen in patients with PD in another independent cohort of 120 PD patients and 120 controls. RESULTS: Microbiota from patients with PD was altered relative to controls and dominated by Verrucomicrobia, Mucispirillum, Porphyromonas, Lactobacillus, and Parabacteroides. In contrast, Prevotella was more abundant in controls. The abundances of Bacteroides were more increased in patients with non-tremor PD subtype than patients with tremor subtype. Bacteroides abundance was correlated with motor symptom severity defined by UPDRS part III motor scores (rho = 0.637 [95% confidence interval 0.474 to 0.758], P < 0.01). Altered microbiota was correlated with plasma concentrations of IFNγ and TNFα. There was a correlation between Bacteroides and plasma level of TNFα (rho = 0.638 [95% CI: 0.102-0.887], P = 0.02); and a correlation between Verrucomicrobia abundance and plasma concentrations of IFNγ (rho = 0.545 [95% CI - 0.043-0.852], P = 0.05). The elevated plasma cytokine responses were confirmed in an additional independent 120 patients with PD and 120 controls (TNFα: PD vs. control 8.51 ± 4.63 pg/ml vs. 4.82 ± 2.23 pg/ml, P < 0.01; and IFNγ: PD vs. control: 38.45 ± 7.12 pg/ml vs. 32.79 ± 8.03 pg/ml, P = 0.03). CONCLUSIONS: This study reveals altered gut microbiota in PD and its correlation with clinical phenotypes and severity in our population. The altered plasma cytokine profiles associated with gut microbiome composition alterations suggest aberrant immune responses may contribute to inflammatory processes in PD.
Experiment 1
Reviewed Marked as Reviewed by Rimsha on 2022/05/15
Subjects
- Location of subjects
- Japan
- 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 without Parkinson's disease
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Participants with Parkinson's Disease
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- PD was diagnosed according to the United Kingdom PD Society Brain Bank clinical diagnostic criteria.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 77
- Group 1 sample size Number of subjects in the case (exposed) group
- 80
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Individuals currently taking antibiotics or probiotic supplements within 3 months of sample collection
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
- LEfSe
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
- Matched on Factors on which subjects have been matched on in a case-control study
- age, sex
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, diet, sex
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- Chao1 Abundance-based estimator of species richness
- unchanged
- Richness Number of species
- increased
Signature 1
Reviewed Marked as Reviewed by Rimsha on 2022/05/15
Source: Figure 3A
Description: Taxonomic differences of fecal microbiota in PD and control groups
Abundance in Group 1: increased abundance in Participants with Parkinson's Disease
Revision editor(s): Fcuevas3
Experiment 2
Reviewed Marked as Reviewed by Rimsha on 2022/05/15
Subjects
- Location of subjects
- Japan
- 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
- Participants with Parkinson's Disease with non-tremor subtypes
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Participants with Parkinson's Disease with tremor subtypes
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Participants with Parkinson's Disease with tremor subtypes.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 33
- Group 1 sample size Number of subjects in the case (exposed) group
- 47
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Individuals currently taking antibiotics or probiotic supplements within 3 months of sample collection
Lab analysis
- Sequencing type
- 16S
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Statistical test
- LEfSe
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
- Matched on Factors on which subjects have been matched on in a case-control study
- age, sex
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, diet, sex
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- Richness Number of species
- increased
Signature 1
Reviewed Marked as Reviewed by Rimsha on 2022/05/15
Source: Figure 4A.
Description: Taxonomic differences of fecal microbiota in non tremor and tremor groups.
Abundance in Group 1: increased abundance in Participants with Parkinson's Disease with tremor subtypes
| NCBI | Links |
|---|---|
| Akkermansia | |
| Clostridia | |
| Clostridiales Family XIII bacterium | |
| Bacillota | |
| Verrucomicrobiota | |
| Verrucomicrobiaceae | |
| Verrucomicrobiae | |
| Verrucomicrobiales |
Signature 2
Reviewed Marked as Reviewed by Rimsha on 2022/05/15
Source: Figure 4A.
Description: Taxonomic differences of fecal microbiota in PD and control groups
Abundance in Group 1: decreased abundance in Participants with Parkinson's Disease with tremor subtypes
| NCBI | Links |
|---|---|
| Alcaligenaceae | |
| Bacteroidales | |
| Bacteroidota | |
| Bacteroidia | |
| Cupriavidus ⚠ | |
| Desulfovibrio | |
| Flavobacterium ⚠ | |
| Mogibacterium | |
| Propionibacterium ⚠ | |
| Sutterella |
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