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, often resulting in motor dysfunction as exemplified by Parkinson’s disease. Using mice overexpressing α-synuclein, Sampson and colleagues report that gut microbiota are required for motor deficits, activation of microglia, and α-synuclein pathology. Antibiotic treatment ameliorates, while microbial re-colonization promotes, pathophysiology in adult animals. Oral administration of specific microbial metabolites to germ-free mice was observed to promote neuroinflammation and motor symptoms. Colonization of α-synuclein-overexpressing mice with microbiota from Parkinson’s disease-affected patients enhanced physical impairments compared to microbiota transplants from healthy human donors. These findings show that gut bacteria can regulate movement disorders in mice and suggest that alterations in the human microbiome represent a risk factor for Parkinson’s disease.
Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, Challis C, Schretter CE, Rocha S, Gradinaru V, Chesselet MF, Keshavarzian A, Shannon KM, Krajmalnik-Brown R, Wittung-Stafshede P, Knight R, Mazmanian SK: Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease. Cell 167(6):1469-1480 (2016).