bioRxiv (Cold Spring Harbor Laboratory) · 2019 · 12 citations · 47 references
Life SciencesBiologyNeuroscienceMolecular NeuroscienceNeurobiology Of DiseaseNeurodegenerationGut MicrobiomeGut MicrobiotaMicrobiome DysbiosisMicrobiome FunctionNeurodegenerative DiseasesParkinson DiseaseDrosophila Disease ModelsDrosophila ModelsGut Microbiota EffectsGut-brain Axis SignalingMicrobial Community CompositionMicrobiome-gut-brain AxisMicrobiome-gut-brain CommunicationMicrobiota-gut-brain Axis
ABSTRACT Drosophila is poised to be a powerful model organism for studies of the gut-brain axis due to the relative simplicity of its microbiota, similarity to mammals, and efficient methods to rear germ-free flies. We examined the gut-brain axis in Drosophila models of autosomal recessive parkinsonism and discovered a relationship between the gut microbiota and parkin loss of function. The number of live bacteria was increased approximately five-fold in the gut of aged parkin null animals. Conditional RNAi showed that parkin is required in gut enterocytes and not in neurons or muscle to maintain microbial load homeostasis. To examine the significance of gut microbiota, we reared germ-free parkin flies and discovered that removal of microbes in the gut improves the animals’ resistance to paraquat. Sequencing of 16S rDNA revealed microbial species with altered relative abundance in parkin null flies compared to controls. These data reveal a role for parkin activity in maintaining microbial composition and abundance in the gut, suggesting a relationship between parkin function and the gut microbiota, and deepening our understanding of parkin and the impacts upon loss of parkin function.
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