Drug-microbiome-host interactions in Parkinson's disease

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The human intestine is inhabited by a complex community of trillions of microbes, together known as the gut microbiota, which influences both host physiology and susceptibility to disease. Accumulating evidence links gut bacteria to pathophysiology of neurodegenerative disorders such as Parkinson's disease (PD), a disease currently affecting 1% of the population over the age of 60. PD predominantly impacts dopaminergic neurons in the brain. Thus, therapies to ameliorate PD symptoms primarily consist of pharmaceutical drugs that replenish dopamine levels. As these drugs are taken orally, they interact with thousands of microbial species present in the gut. Indeed, large-scale screenings have revealed a significant proportion of human-targeted drugs, including PD drugs, reach the intestine at concentrations that can inhibit growth of several gut bacteria in vitro. Additionally, diarrhea and constipation are common side effects of PD drugs. Altogether, these findings underscore the potential of PD-targeted drugs in shaping the gut microbiome, but the direct impact of these drugs on complex microbiota communities is not known.This interdisciplinary project aims to investigate in detail i) the impact of PD drugs on composition and activity of the human gut microbiota and ii) the repercussions this may have on the host. The project will employ state-of-the-art microbial ecology techniques such as ex vivo anaerobic incubations, microbial ecophysiology methods, next-generation sequencing and bioinformatics. The role of the microbiota on the effectiveness of the drugs will be evaluated in vivo, using a transgenic mouse model of PD in combination with microbiota manipulation procedures.Results from this interdisciplinary project will advance our understanding of how PD drugs shape the microbiome and potentially identify key microbiome players that can be manipulated to augment the effectiveness of current PD therapies.The ideal candidate must be primarily interested in microbiology and be willing to do a few animal experiments.