Published online Oct 7, 2015. doi: 10.3748/wjg.v21.i37.10609
Peer-review started: March 3, 2015
First decision: May 18, 2015
Revised: May 28, 2015
Accepted: August 31, 2015
Article in press: August 31, 2015
Published online: October 7, 2015
Parkinson’s disease (PD) is characterized by alpha-synucleinopathy that affects all levels of the brain-gut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that the brain-gut axis interactions are significantly modulated by the gut microbiota via immunological, neuroendocrine, and direct neural mechanisms. Dysregulation of the brain-gut-microbiota axis in PD may be associated with gastrointestinal manifestations frequently preceding motor symptoms, as well as with the pathogenesis of PD itself, supporting the hypothesis that the pathological process is spread from the gut to the brain. Excessive stimulation of the innate immune system resulting from gut dysbiosis and/or small intestinal bacterial overgrowth and increased intestinal permeability may induce systemic inflammation, while activation of enteric neurons and enteric glial cells may contribute to the initiation of alpha-synuclein misfolding. Additionally, the adaptive immune system may be disturbed by bacterial proteins cross-reacting with human antigens. A better understanding of the brain-gut-microbiota axis interactions should bring a new insight in the pathophysiology of PD and permit an earlier diagnosis with a focus on peripheral biomarkers within the enteric nervous system. Novel therapeutic options aimed at modifying the gut microbiota composition and enhancing the intestinal epithelial barrier integrity in PD patients could influence the initial step of the following cascade of neurodegeneration in PD.
Core tip: Parkinson’s disease (PD) is characterized by alpha-synucleinopathy affecting all levels of the brain-gut axis. Both clinical and neuropathological evidences indicate that neurodegenerative changes in PD are accompanied by gastrointestinal symptoms that may precede or follow the central nervous system impairment. Dysregulation of the brain-gut-microbiota axis may significantly contribute to the pathogenesis of PD. The gut seems to play a critical role in the pathophysiology of PD representing a rout of entry for a putative environmental factor to initiate the pathological process. The close relationship between gut dysbiosis, intestinal permeability and neurological dysfunction suggests that the gut microbiota modification may provide a promising therapeutic option in PD.