The gut-brain axis: is intestinal inflammation a silent driver of Parkinson's disease pathogenesis?

• Type of Material: Article
• Authors: Madelyn C. Houser, Emory University; Malu Tansey, Emory University
• Language: English
• Date: 2017
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2017
• Final Published Version (URL): http://dx.doi.org/10.1038/s41531-016-0002-0
• Title of Journal or Parent Work: npj Parkinson's Disease
• ISSN: 2373-8057
• Volume: 3
• Start Page: 3
• End Page: 3
• Grant/Funding Information: This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-1444932 (MCH), the Parkinson’s Disease Foundation, the Michael J. Fox Foundation for Parkinson’s Research, and the NIH-NINDS under Grant No. 5R01NS092122 (MGT).
• Research Categories: Biology, Neuroscience; Health Sciences, Medicine and Surgery

Abstract

The state of the intestinal environment can have profound effects on the activity of the central nervous system through the physiological contributions of the microbiota, regulation of intestinal barrier function, and altered activity of peripheral neurons. The common language employed for much of the gut-brain communication is the modulation of immune activity. Chronic proinflammatory immune activity is increasingly being recognized as a fundamental element of neurodegenerative disorders, and in Parkinson's disease, inflammation in the intestine appears particularly relevant in pathogenesis. We review the evidence that intestinal dysfunction is present in Parkinson's disease and that it may reflect the earliest manifestations of Parkinson's disease pathology, and we link these findings to dysregulated immune activity. Based on this, we present a model for Parkinson's disease pathogenesis in which the disorder originates in the intestine and progresses with inflammation as its underlying mechanism. More in-depth investigations into the physiological mechanisms underlying peripheral pre-motor symptoms in Parkinson's disease are expected to lead to the development of novel diagnostic and therapeutic measures that can slow or limit progression of the disease to more advanced stages involving debilitating motor and cognitive symptoms.