Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease

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 tran..., HumanizedMotorFunctionMotor function scores of wild-type and Thy1-aSyn mice colonized with fecal microbes derived from Parkinson's disease patients or matched healthy controls.MouseTreatmentMotorFunctionMotor function scores of wild-type and Thy1-aSyn mice, under differing microbial colonization status. Conventionally colonized, germ-free, antibiotic-treated, recolonized germ-free, and short-chain fatty acid treated animals.SynucleinandInflammationExpression and production of alpha-synuclein and proinflammatory cytokines, and microglia diameter and cytokine expression in the brain of wild-type and Thy1-aSyn mice, under specific pathogen free and germ-free conditions., , , Dryad has been alerted to concerns over duplicate data between the regular and re-colonised biome conditions in the dataset, and where the dataset supports this published paper [1]. We are liaising with the corresponding authors over these concerns (they have been asked to inform their co-authors), with the intention to publish a revised dataset. Dryad is therefore posting this Expression of concern, of which the corresponding authors have been informed, and while we collaborate with both them and Cell.
[1]: Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease. Sampson, T.R., Debelius, J.W., Thron, T., et al. Cell, Volume 167, Issue 6, 1469-1480.e12. Published 1 December 2016. DOI: 10.1016/j.cell.2016.11.018