Project 459033

Parkinson's disease (PD) is the second most common neurodegenerative disorder in the world, causing motor dysfunction that worsens over time. Gut changes are experienced by nearly all PD patients, and can predate diagnosis by several decades. The types of bacteria present in the gut are different between PD patients and neurotypical people, meaning that bacteria may play an important role in PD development. Akkermansia muciniphila is a bacterium that is usually associated with reduced inflammation, but is enriched in the guts of PD patients and can increase gut inflammation in specific contexts. Akkermansia strongly influences the immune system, which may help to mitigate bacterial infections and in turn reduce PD risk. There are many strains (types) of Akkermansia; while most research has focused on one strain, evidence suggests that different strains have different effects on the human host. I propose to characterize the genetic and functional differences between Akkermansia strains that have been isolated from PD patients and neurotypical people, and determine whether PD-derived strains are associated with worse inflammation during intestinal infection. I will first compare the genomes of eight newly-isolated Akkermansia strains with 39 publicly-available strains in order to determine whether PD strains form a distinct group. I will then characterize their growth and their interaction with host immune system. Select strains of interest will be transferred into mice, who will then be infected with an intestinal pathogen. Infection severity will be monitored, and specific biochemical tests will be used to explore corresponding immune mechanisms. Finally, I will try to promote anti-inflammatory immune mechanisms in these mice using nutritional supplements. Understanding whether PD-derived Akkermansia differs from other strains will help determine the significance of gut bacteria in PD and contribute to the development of effective Akkermansia probiotic therapies.