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

Timothy R Sampson ; Justine W Debelius ; Taren Thron ; Stefan Janssen ; Gauri G Shastri ; Zehra Esra Ilhan ; Collin Challis ; Catherine E Schretter ; Sandra Rocha (Institutionen för biologi och bioteknik, Kemisk biologi) ; Viviana Gradinaru ; Marie-Francoise Chesselet ; Ali Keshavarzian ; Kathleen M Shannon ; Rosa Krajmalnik-Brown ; Pernilla Wittung-Stafshede (Institutionen för biologi och bioteknik, Kemisk biologi) ; Rob Knight ; Sarkis K Mazmanian
Cell (1097-4172). Vol. 167 (2016), 6, p. 1469-1480.e12.
[Artikel, refereegranskad vetenskaplig]

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.



Denna post skapades 2016-12-22. Senast ändrad 2017-10-03.
CPL Pubid: 246457

 

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Institutioner (Chalmers)

Institutionen för biologi och bioteknik, Kemisk biologi

Ämnesområden

Biofysik
Neurobiologi
Cellbiologi

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