Study Rationale:
Development of Parkinson’s Disease (PD) involves genetic and environmental factors. Not all people with genetic risk factors for PD develop the disease. Additional factors like gastrointestinal infections and inflammation and gut microbiome disbalance are associated with disease progression. This study aims to determine how changes in gut microbiome composition influences disease progression in people genetically predisposed to PD.
Hypothesis:
The gut microbiome plays an intermediary role between gastrointestinal inflammation, immune autoreactivity and genetic susceptibility in Parkinson’s Disease progression.
Study Design:
We will use our novel models of gastrointestinal infection-induced motor dysfunction in preclinical models lacking gene Pink1, mutations in which have been associated with early onset PD in humans. About 70% of preclinical models in this model develop PD-like symptoms after infection with gastrointestinal bacteria. Preliminary data show that the PD-like disease in preclinical is associated with certain microbiome components that remain in the gut long after infection is cleared. We will trace in depth changes in microbiome after infection and correlate it to the disease progression.
Impact on Diagnosis/Treatment of Parkinson’s disease:
Potential candidate bacteria of the microbiome will be determined during this study as well as the major mechanism of inflammation initiation. This will allow us to further validate our prospective results in human patients and potentially use microbiome tracing as a non-invasive marker for PD diagnosis. Correction of microbiome changes or inflammation initiated by certain microbes might be the next treatment for PD.
Next Steps for Development:
Results of this study will give us new directions to follow up in humans with PD and their household neighbors. If successful this study could change the paradigm of PD treatment, not only as a pure neurological disease but as a complex brain-immune-gut microbiome dysregulation requiring corrections on all levels involved for the better treatment of PD.