Fig. 1.

Model of gut-originating, inflammation-driven PD pathogenesis. In a susceptible individual, inflammatory triggers (1) initiate immune responses in the gut that deleteriously impact the microbiota, increase intestinal permeability, and induce increased expression and aggregation of αSYN (2). Synucleinopathy may be transmitted from the gut to the brain via the vagus nerve (3b), and chronic intestinal inflammation and permeability promote systemic inflammation, which, among other things, can increase blood-brain barrier permeability (3a). Intestinal inflammation, systemic inflammation, and synuclein pathology in the brain all promote neuroinflammation (4) which drives the neurodegeneration that characterizes PD (5)