The alteration of intestinal mucosal α-synuclein expression and mucosal microbiota in Parkinson's disease

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Reviewed Marked as Reviewed by Svetlana up on 2024-7-3
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


Reviewed Marked as Reviewed by Svetlana up on 2024-7-3

Curated date: 2024/03/12

Curator: Scholastica

Revision editor(s): Scholastica

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 (PD) Patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Parkinson's disease (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

Reviewed Marked as Reviewed by Svetlana up on 2024-7-3

Curated date: 2024/03/12

Curator: Scholastica

Revision editor(s): Scholastica

Source: Figure 5c

Description: Taxa significantly abundant in the duodenal mucosal microbiota composition in control versus Parkinson's disease (PD) patients

Abundance in Group 1: increased abundance in Parkinson's Disease (PD) Patients

NCBI Quality ControlLinks
Burkholderiaceae
Burkholderiales
Gammaproteobacteria
Lactococcus
Massilia
Oxalobacteraceae
Pseudomonadota
Ralstonia

Revision editor(s): Scholastica

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-7-3

Curated date: 2024/03/12

Curator: Scholastica

Revision editor(s): Scholastica

Source: Figure 5c

Description: Taxa significantly abundant in the duodenal mucosal microbiota composition in control versus Parkinson's disease (PD) patients

Abundance in Group 1: decreased abundance in Parkinson's Disease (PD) Patients

NCBI Quality ControlLinks
Flavobacteriaceae
Rhodospirillales
CAG56CAG56

Revision editor(s): Scholastica

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2024-7-3

Curated date: 2024/03/12

Curator: Scholastica

Revision editor(s): Scholastica

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 1 name Corresponds to the case (exposed) group for case-control studies
Parkinson's Disease Patients
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

Reviewed Marked as Reviewed by Svetlana up on 2024-7-3

Curated date: 2024/03/12

Curator: Scholastica

Revision editor(s): Scholastica

Source: Figure 5d

Description: Taxa significantly abundant in the sigmoid mucosal microbiota composition in control versus Parkinson's disease (PD) patients

Abundance in Group 1: increased abundance in Parkinson's Disease Patients

NCBI Quality ControlLinks
Bifidobacterium longum
Prevotellaceae

Revision editor(s): Scholastica

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-7-3

Curated date: 2024/03/12

Curator: Scholastica

Revision editor(s): Scholastica

Source: Figure 5d

Description: Taxa significantly abundant in the sigmoid mucosal microbiota composition in control versus Parkinson's disease (PD) patients

Abundance in Group 1: decreased abundance in Parkinson's Disease Patients

NCBI Quality ControlLinks
Thermoactinomycetaceae
ThermoactinomycetalesThermoactinomycetales

Revision editor(s): Scholastica

Experiment 3


Reviewed Marked as Reviewed by Svetlana up on 2024-7-3

Curated date: 2024/03/13

Curator: Scholastica

Revision editor(s): Scholastica

Differences from previous experiment shown

Subjects

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
Samples from the sigmoid mucosa of Parkinson's disease (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