The alteration of intestinal mucosal α-synuclein expression and mucosal microbiota in 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
Shi J, Wang Y, Chen D, Xu X, Li W, Li K, He J, Su W, Luo Q
Journal
Applied microbiology and biotechnology
Year
2023
Keywords:
Diagnosis, Intestinal mucosa, Mucosal microbiota, Parkinson’s disease, α-Synuclein
Parkinson's disease (PD) is the second most common neurodegenerative disease but still lacks a preclinical strategy to identify it. The diagnostic value of intestinal mucosal α-synuclein (αSyn) in PD has not drawn a uniform conclusion. The relationship between the alteration of intestinal mucosal αSyn expression and mucosal microbiota is unclear. Nineteen PD patients and twenty-two healthy controls were enrolled in our study from whom were collected, using gastrointestinal endoscopes, duodenal and sigmoid mucosal samples for biopsy. Multiplex immunohistochemistry was performed to detect total, phosphorylate, and oligomer α-synuclein. Next-generation 16S rRNA amplicon sequencing was applied for taxonomic analysis. The results implied that oligomer α-synuclein (OSyn) in sigmoid mucosa of PD patients was transferred from the intestinal epithelial cell membrane to the cytoplasm, acinar lumen, and stroma. Its distribution feature was significantly different between the two groups, especially the ratio of OSyn/αSyn. The microbiota composition in mucosa also differed. The relative abundances of Kiloniellales, Flavobacteriaceae, and CAG56 were lower, while those of Proteobacteria, Gammaproteobacteria, Burkholderiales, Burkholdriaceae, Oxalobacteraceae, Ralstonia, Massilla, and Lactoccus were higher in duodenal mucosa of PD patients. The relative abundances of Thermoactinomycetales and Thermoactinomycetaceae were lower, while those of Prevotellaceae and Bifidobacterium longum were higher in patients' sigmoid mucosa. Further, the OSyn/αSyn level was positively correlated with the relative abundances of Proteobacteria, Gammaproteobacteria, Burkholderiales, Pseudomonadales, Burkholderiaceae, and Ralstonia in the duodenal mucosa, while it was negatively correlated with the Chao1 index and observed operational taxonomic units of microbiota in sigmoid mucosa. The intestinal mucosal microbiota composition of PD patients altered with the relative abundances of proinflammatory bacteria in the duodenal mucosa increased. The ratio of the OSyn/αSyn level in the sigmoid mucosa indicated a potential diagnostic value for PD, which also correlated with mucosal microbiota diversity and composition. KEY POINTS: • The distribution of OSyn in sigmoid mucosa differed between PD patients and healthy controls. • Significant alterations in the microbiome were found in PD patients' gut mucosa. • OSyn/αSyn level in sigmoid mucosa indicated a potential diagnostic value for PD.
Experiment 1
Needs review
Subjects
- Location of subjects
- China
- 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
- Duodenal mucosa Doudenal mucosa,Duodenal mucous membrane,Duodenum mucosa,Mucosa of duodenum,Mucous membrane of duodenum,Duodenal mucosa,duodenal mucosa
- 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 Patients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- PD patients diagnosed by an experienced neurologist (the stage of Hoehn and Yahr Scale < 5)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 22
- Group 1 sample size Number of subjects in the case (exposed) group
- 19
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- None
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).
- relative abundances
- Statistical test
- LEfSe
- 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
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 4
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
Signature 1
Needs review
Source: Figure 5c, Text (Taxonomic analysis of mucosal microbiota composition among different groups)
Description: Duodenal mucosal microbiota composition and differential species analysis
Abundance in Group 1: increased abundance in Parkinson's Disease Patients
| NCBI | Quality Control | Links |
|---|---|---|
| Burkholderiaceae | ||
| Burkholderiales | ||
| Gammaproteobacteria | ||
| Lactococcus | ||
| Massilia | ||
| Oxalobacteraceae | ||
| Pseudomonadota | ||
| Ralstonia |
Revision editor(s): Scholastica
Signature 2
Needs review
Source: Figure 5c, Text (Taxonomic analysis of mucosal microbiota composition among different groups)
Description: Duodenal mucosal microbiota composition and differential species analysis
Abundance in Group 1: decreased abundance in Parkinson's Disease Patients
| NCBI | Quality Control | Links |
|---|---|---|
| Rhodospirillales | ||
| CAG56CAG56 | ||
| Flavobacteriaceae |
Revision editor(s): Scholastica
Experiment 2
Needs review
Differences from previous experiment shown
Subjects
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Mucosa of sigmoid colon Mucosa of organ of sigmoid colon,Mucous membrane of sigmoid colon,Organ mucosa of sigmoid colon,Sigmoid colon mucosa,Sigmoid colon mucosa of organ,Sigmoid colon mucous membrane,Sigmoid colon organ mucosa,Mucosa of sigmoid colon,mucosa of sigmoid colon
- Group 0 sample size Number of subjects in the control (unexposed) group
- 21
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
Signature 1
Needs review
Source: Figure 5d, Text (Taxonomic analysis of mucosal microbiota composition among different groups)
Description: Sigmoid mucosal microbiota composition and differential species analysis
Abundance in Group 1: increased abundance in Parkinson's Disease Patients
| NCBI | Quality Control | Links |
|---|---|---|
| Prevotellaceae | ||
| Bifidobacterium longum |
Revision editor(s): Scholastica
Signature 2
Needs review
Source: Figure 5d, Text (Taxonomic analysis of mucosal microbiota composition among different groups)
Description: Sigmoid mucosal microbiota composition and differential species analysis
Abundance in Group 1: decreased abundance in Parkinson's Disease Patients
| NCBI | Quality Control | Links |
|---|---|---|
| Thermoactinomycetaceae | ||
| ThermoactinomycetalesThermoactinomycetales |
Revision editor(s): Scholastica
Experiment 3
Needs review
Differences from previous experiment shown
Subjects
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Duodenal mucosa , Mucosa of sigmoid colon Doudenal mucosa,Duodenal mucous membrane,Duodenum mucosa,Mucosa of duodenum,Mucous membrane of duodenum,Duodenal mucosa,duodenal mucosa,Mucosa of organ of sigmoid colon,Mucous membrane of sigmoid colon,Organ mucosa of sigmoid colon,Sigmoid colon mucosa,Sigmoid colon mucosa of organ,Sigmoid colon mucous membrane,Sigmoid colon organ mucosa,Mucosa of sigmoid colon,mucosa of sigmoid colon
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Duodenal mucosa
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Sigmoid mucosa
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Sigmoid mucosa of PD patients
- Group 0 sample size Number of subjects in the control (unexposed) group
- 19
Lab analysis
Statistical Analysis
- Statistical test
- Kruskall-Wallis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- increased
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