Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of 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
Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, Challis C, Schretter CE, Rocha S, Gradinaru V, Chesselet MF, Keshavarzian A, Shannon KM, Krajmalnik-Brown R, Wittung-Stafshede P, Knight R, Mazmanian SK
Journal
Cell
Year
2016
Keywords:
Parkinson’s disease, gut-brain axis, microbiome, microglia, mouse model, short chain fatty acids, synuclein
The intestinal microbiota influence neurodevelopment, modulate behavior, and contribute to neurological disorders. However, a functional link between gut bacteria and neurodegenerative diseases remains unexplored. Synucleinopathies are characterized by aggregation of the protein α-synuclein (αSyn), often resulting in motor dysfunction as exemplified by Parkinson's disease (PD). Using mice that overexpress αSyn, we report herein that gut microbiota are required for motor deficits, microglia activation, and αSyn pathology. Antibiotic treatment ameliorates, while microbial re-colonization promotes, pathophysiology in adult animals, suggesting that postnatal signaling between the gut and the brain modulates disease. Indeed, oral administration of specific microbial metabolites to germ-free mice promotes neuroinflammation and motor symptoms. Remarkably, colonization of αSyn-overexpressing mice with microbiota from PD-affected patients enhances physical impairments compared to microbiota transplants from healthy human donors. These findings reveal that gut bacteria regulate movement disorders in mice and suggest that alterations in the human microbiome represent a risk factor for PD.
Experiment 1
Reviewed Marked as Reviewed by Svetlana up on 2024-4-5
Subjects
- Location of subjects
- United States of America
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Mus musculus
- 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
- Wild-type (WT) mice with fecal microbes from healthy controls (HC)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Wild-type (WT) mice with fecal microbes from Parkinson’s disease patients (PD)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Germ-free wild-type (WT) mice colonized with fecal microbes from Parkinson’s disease patients (PD)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 6
- Group 1 sample size Number of subjects in the case (exposed) group
- 6
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).
- centered log-ratio
- Statistical test
- ANCOM
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-4-5
Source: Figure 6E
Description: Differentially abundant taxon in the WT mice with HC fecal transfer and the WT mice with PD fecal transfer.
Abundance in Group 1: increased abundance in Wild-type (WT) mice with fecal microbes from Parkinson’s disease patients (PD)
| NCBI | Quality Control | Links |
|---|---|---|
| Enterococcus | ||
| Peptococcaceae rc4-4 sp.Peptococcaceae rc4-4 sp. | ||
| Pseudoramibacter |
Revision editor(s): Toyosiolann, Svetlana up
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2024-4-5
Source: Figure 6E
Description: Differentially abundant taxon in the WT mice with HC fecal transfer and the WT mice with PD fecal transfer.
Abundance in Group 1: decreased abundance in Wild-type (WT) mice with fecal microbes from Parkinson’s disease patients (PD)
| NCBI | Quality Control | Links |
|---|---|---|
| Butyricimonas | ||
| Roseburia | ||
| unsp. Rikenellaceaeunsp. Rikenellaceae |
Revision editor(s): Toyosiolann, Svetlana up
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2024-4-5
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- ASO mice with fecal microbes from healthy controls (HC)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- ASO mice with fecal microbes from Parkinson’s disease patients (PD)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Germ-free mice, Thy1-α-synuclein genotype (ASO) colonized with fecal microbes from Parkinson’s disease patients (PD)
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-4-5
Source: Figure 6E
Description: Differentially abundant taxon in the ASO mice with HC fecal transfer and the ASO mice with PD fecal transfer.
Abundance in Group 1: increased abundance in ASO mice with fecal microbes from Parkinson’s disease patients (PD)
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroides | ||
| Bilophila | ||
| Enterococcus | ||
| Proteus | ||
| unsp.Veillonellaceaeunsp.Veillonellaceae | ||
| Peptococcaceae rc4-4 sp.Peptococcaceae rc4-4 sp. | ||
| Pseudoramibacter |
Revision editor(s): Svetlana up
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2024-4-5
Source: Figure 6E
Description: Differentially abundant taxon in the ASO mice with HC fecal transfer and the ASO mice with PD fecal transfer.
Abundance in Group 1: decreased abundance in ASO mice with fecal microbes from Parkinson’s disease patients (PD)
Revision editor(s): Svetlana up
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