Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 7, 2015; 21(37): 10609-10620
Published online Oct 7, 2015. doi: 10.3748/wjg.v21.i37.10609
Brain-gut-microbiota axis in Parkinson's disease
Agata Mulak, Bruno Bonaz
Agata Mulak, Department of Gastroenterology and Hepatology, Wroclaw Medical University, 50-556 Wroclaw, Poland
Bruno Bonaz, Grenoble Institut des Neurosciences (GIN), INSERM U836, 38043 Grenoble, France
Bruno Bonaz, Clinique Universitaire d’Hépato-Gastroentérologie, CHU de Grenoble, 38043 Grenoble, France
Author contributions: Mulak A designed and wrote the paper; Bonaz B designed, wrote and reviewed the paper.
Conflict-of-interest statement: There is no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Agata Mulak, MD, PhD, Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland.
Telephone: +48-71-7332120 Fax: +48-71-7332129
Received: March 2, 2015
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.

Keywords: Brain-gut-microbiota axis, Enteric nervous system, Gastrointestinal dysfunction, Gut microbiota, Parkinson’s disease

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.