Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease.
Artikel i vetenskaplig tidskrift, 2016

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.

Författare

Timothy R Sampson

CalTech

Justine W Debelius

University of California

Taren Thron

CalTech

Stefan Janssen

University of California

Gauri G Shastri

CalTech

Zehra Esra Ilhan

Arizona State University

Collin Challis

CalTech

Catherine E Schretter

CalTech

Sandra Rocha

Chalmers, Biologi och bioteknik, Kemisk biologi

Viviana Gradinaru

CalTech

Marie-Francoise Chesselet

David Geffen School of Medicine at UCLA

Ali Keshavarzian

Rush University Medical Center

Kathleen M Shannon

Rush University Medical Center

Rosa Krajmalnik-Brown

Arizona State University

Pernilla Wittung Stafshede

Chalmers, Biologi och bioteknik, Kemisk biologi

Rob Knight

University of California

Sarkis K Mazmanian

CalTech

Cell

0092-8674 (ISSN) 1097-4172 (eISSN)

Vol. 167 6 1469-1480.e12

Ämneskategorier

Neurovetenskaper

Cell- och molekylärbiologi

Biofysik

DOI

10.1016/j.cell.2016.11.018

PubMed

27912057