Title:Finding Catalysts of Gut Reactions: The Gut Microbiota i n Disease Onset and Treatment

Accumulation of α-synuclein protein aggregates in brain neurons is thought to result in Parkinson’s

disease. Despite the clear impact that this disease has on the brain, it seems that the disease as well as α-

synuclein aggregates may originate somewhere else— in the gut. Each person’s gut houses trillions of

bacteria. Our data show that these gut bacteria start a domino-effect that can cause aggregation of α-

synuclein in intestinal cells that natively express this protein. Emerging from our discovery of molecularlevel

mechanisms detailing how gut bacteria cause α- synuclein aggregation, we identified diet-derived small

molecules that inhibit formation of α-synuclein aggregates in intestinal cells. Our discoveries suggest

that microbiome-targeted treatments may be developed to slow progression of Parkinson’s disease

or even stop the disease in the gut before it impacts the brain.