Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease

Study information

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Reviewed Marked as Reviewed by Svetlana up on 2024-4-5

study design

laboratory experiment

Citation

PMID PubMed identifier for scientific articles.

27912057

DOI Digital object identifier for electronic documents.

https://doi.org/10.1016%2Fj.cell.2016.11.018

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

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Curated date: 2024/03/08

Curator: Toyosiolann

Revision editor(s): Toyosiolann, Svetlana up, WikiWorks

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

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

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Curated date: 2024/03/20

Curator: Toyosiolann

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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, WikiWorks

Signature 2

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Curated date: 2024/03/20

Curator: Toyosiolann

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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, WikiWorks

Experiment 2

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Curated date: 2024/04/02

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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

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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, WikiWorks

Signature 2

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Reviewed Marked as Reviewed by Svetlana up on 2024-4-5

Curated date: 2024/04/02

Curator: Svetlana up

Revision editor(s): Svetlana up, WikiWorks

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)

NCBI	Quality Control	Links
Butyricicoccus
Clostridium
Roseburia
unsp. Lachnospiraceaeunsp. Lachnospiraceae
unsp. Rikenellaceaeunsp. Rikenellaceae
unsp. Peptostreptococcaceaeunsp. Peptostreptococcaceae
unsp. Clostridiaceaeunsp. Clostridiaceae

Revision editor(s): Svetlana up, WikiWorks