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Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease
- Source :
- Cell, vol 167, iss 6
- Publication Year :
- 2016
- Publisher :
- Elsevier, 2016.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Aging
Parkinson's disease
microbiome
microglia
Neurodegenerative
Gut flora
Medical and Health Sciences
Oral and gastrointestinal
Hypotension, Orthostatic
Mice
chemistry.chemical_compound
0302 clinical medicine
2.1 Biological and endogenous factors
Aetiology
Parkinson's Disease
biology
gut-brain axis
Fatty Acids
Brain
Parkinson Disease
Biological Sciences
Neurological
alpha-Synuclein
Microglia
mouse model
Gut–brain axis
digestive system
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
synuclein
medicine
Animals
Humans
Microbiome
Neuroinflammation
Inflammation
Alpha-synuclein
Synucleinopathies
Prevention
Neurosciences
medicine.disease
biology.organism_classification
Gastrointestinal Microbiome
Brain Disorders
Gastrointestinal Tract
030104 developmental biology
chemistry
Immunology
Parkinson’s disease
Dysbiosis
short chain fatty acids
030217 neurology & neurosurgery
Developmental Biology
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cell, vol 167, iss 6
- Accession number :
- edsair.doi.dedup.....b0b7fe5563898f8ce8181ca26f7977c6
- Full Text :
- https://doi.org/10.1016/j.cell.2016.11.018