Altered Gut Microbiome in Parkinson's Disease and the Influence of Lipopolysaccharide in a Human α-Synuclein Over-Expressing Mouse Model

Study information

Reviewed Marked as Reviewed by Claregrieve1 on 2022/07/5

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

31440136

DOI Digital object identifier for electronic documents.

10.3389/fnins.2019.00839

URI

Authors

Gorecki AM, Preskey L, Bakeberg MC, Kenna JE, Gildenhuys C, MacDougall G, Dunlop SA, Mastaglia FL, Akkari PA, Koengten F, Anderton RS

Journal

Frontiers in neuroscience

Year

2019

Keywords:

Gammaproteobacteria, Parkinson’s disease, Thy1-αSyn, gastrointestinal, lipopolysaccharide, microbiome

The interaction between the gut microbiota and alpha-synuclein (αSyn) aggregation in Parkinson's disease (PD) is receiving increasing attention. The objective of this study was to investigate gut microbiota, and effects of an inflammatory lipopolysaccharide (LPS) trigger in a human αSyn over-expressing mouse model of PD (Thy1-αSyn). Stool samples from patients with confirmed PD and Thy1-αSyn mice were analyzed using 16S ribosomal RNA sequencing. Compared to healthy controls, the relative abundance of mucin-degrading Verrucomicrobiae and LPS-producing Gammaproteobacteria were greater in PD patients. In mice, the abundance of Gammaproteobacteria was negligible in both Thy1-αSyn and wild-type (WT) animals, while Verrucomicrobiae were reduced in Thy1-αSyn mice. The effect of LPS on intestinal barrier function was investigated in vitro using intestinal epithelial (IEC-6) cells, and in vivo via administration of LPS in drinking water to Thy1-αSyn mice. Acute exposure to LPS in vitro resulted in a reduction and altered distribution of the tight junction markers ZO-1 and e-Cadherin around the cell membrane in IEC-6 cells, as shown by immunohistochemistry. LPS administration in Thy1-αSyn mice resulted in the emergence of early motor manifestations at 10 weeks, compared to untreated mice who were still asymptomatic at this age. This study reaffirms that an altered microbiome exists in patients with PD, and supports the notion of a proinflammatory gut microbiome environment as a trigger for PD pathogenesis.

Experiment 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/07/5

Curated date: 2022/01/22

Curator: Fcuevas3

Revision editor(s): WikiWorks, Claregrieve1, Fcuevas3, Peace Sandy

Subjects

Location of subjects: Australia

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: Participants with idiopathic Parkinson's Disease and mild symptoms.

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: All patients were confirmed to have idiopathic Parkinson’s disease by a movement disorders neurologist, in accordance with the United Kingdom Brain Bank criteria and mild symptoms.

Group 0 sample size Number of subjects in the control (unexposed) group: 7

Group 1 sample size Number of subjects in the case (exposed) group: 7

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): No history of antibiotic or non-steroidal anti-inflammatory drug use in the previous 3 months.

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

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: Mann-Whitney (Wilcoxon)

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

Signature 1

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Source: Figure 1.

Description: Mean class abundance in people with Parkinson’s disease and healthy controls, specifically control vs. mild PD.

Abundance in Group 1: increased abundance in Participants with idiopathic Parkinson's Disease and mild symptoms.

NCBI	Quality Control	Links
Gammaproteobacteria

Revision editor(s): Fcuevas3

Experiment 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/07/5

Curated date: 2022/01/22

Curator: Fcuevas3

Revision editor(s): Fcuevas3, WikiWorks, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Participants with mild PD

Group 1 name Corresponds to the case (exposed) group for case-control studies: Participants with severe PD

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: All patients were confirmed to have idiopathic Parkinson’s disease by a movement disorders neurologist, in accordance with the United Kingdom Brain Bank criteria and severe symptoms.