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Cell. 2016 Dec 1;167(6):1469-1480.e12. doi: 10.1016/j.cell.2016.11.018.

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

Author information

1
Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: trsamps@caltech.edu.
2
Department of Pediatrics, University of California, San Diego, San Diego, CA 92110, USA.
3
Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
4
Swette Center for Environmental Biotechnology, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
5
Biology and Biological Engineering Department, Chalmers University of Technology, Gothenburg 41296, Sweden.
6
Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
7
Department of Internal Medicine, Division of Gastroenterology, Rush University Medical Center, Chicago, IL 60612, USA.
8
Department of Neurological Sciences, Section of Movement Disorders, Rush University Medical Center, Chicago, IL 60612, USA.
9
Department of Pediatrics, University of California, San Diego, San Diego, CA 92110, USA; Department of Computer Science and Engineering, University of California, San Diego, San Diego, CA 92093, USA.
10
Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: sarkis@caltech.edu.

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.

KEYWORDS:

Parkinson’s disease; gut-brain axis; microbiome; microglia; mouse model; short chain fatty acids; synuclein

PMID:
27912057
PMCID:
PMC5718049
DOI:
10.1016/j.cell.2016.11.018
[Indexed for MEDLINE]
Free PMC Article

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