Figure 1.

Enteric glia, gut dysfunction and neuroimmune mechanisms to gut-brain axis sensitization. On the left, are the classic pre-motor and non-motor symptoms of the prodromal phase of PD. Both glial reactivity and inflammation are strongly implicated in the neurodegenerative process and contribute to pathology progression. Dysbiosis adds to this scenario as another pro-inflammatory element. (A) Enteric glia phenotype and inflammatory signature verified in biopsy samples from PD patients and PD animal models. (B) The condition of leaky gut is evidenced by the disruption of the IEB, given the alteration of the tight junction, thus promoting an increase in intestinal permeability—which should reinforce, reciprocally, the intestinal dysbiosis observed during PD. Subsequent immune activation is one of the gut-brain axis signaling pathways. (C) Exposure to bacterial bioproducts as well as the reduction of microbe-derived beneficial factors (such as SCFA) to the nervous system, reinforce the pro-inflammatory condition and modify the axis based on signaling by biofilm and its derivatives. (D) Enteric glial mechanisms are recognized in PD and/or IBD associated with pro-inflammatory action, dysmotility, and visceral pain.