Cell
Volume 167, Issue 6, 1 December 2016, Pages 1469-1480.e12
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Article
Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease

https://doi.org/10.1016/j.cell.2016.11.018Get rights and content
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Highlights

  • Gut microbes promote α-synuclein-mediated motor deficits and brain pathology

  • Depletion of gut bacteria reduces microglia activation

  • SCFAs modulate microglia and enhance PD pathophysiology

  • Human gut microbiota from PD patients induce enhanced motor dysfunction in mice

Summary

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

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

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Present address: Department of Neurology, University of Wisconsin-Madison, Madison, WI 53705, USA

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