Review: The Role of Intestinal Dysbiosis in Parkinson's Disease

Abstract

Several studies have highlighted the roles played by the gut microbiome in central nervous system diseases. Clinical symptoms and neuropathology have suggested that Parkinson's disease may originate in the gut, which is home to approximately 100 trillion microbes. Alterations in the gastrointestinal microbiota populations may promote the development and progression of Parkinson's disease. Here, we reviewed existing studies that have explored the role of intestinal dysbiosis in Parkinson's disease, focusing on the roles of microbiota, their metabolites, and components in inflammation, barrier failure, microglial activation, and α-synuclein pathology. We conclude that there are intestinal dysbiosis in Parkinson's disease. Intestinal dysbiosis is likely involved in the pathogenesis of Parkinson's disease through mechanisms that include barrier destruction, inflammation and oxidative stress, decreased dopamine production, and molecular mimicry. Additional studies remain necessary to explore and verify the mechanisms through which dysbiosis may cause or promote Parkinson's disease. Preclinical studies have shown that gastrointestinal microbial therapy may represent an effective and novel treatment for Parkinson's disease; however, more studies, especially clinical studies, are necessary to explore the curative effects of microbial therapy in Parkinson's disease.

Keywords: Parkinson’s disease; inflammation; intestinal dysbiosis; molecular mimicry; α-synuclein.

Figure 1

The possible mechanisms of Parkinson’s disease caused by intestinal dysbiosis. The increased intestinal permeability: The decrease of SCFAs concentration in intestinal cavity leads to local inflammation, and also affects the expression of tight junction proteins, including claudin 1 and claudin 2. The increased BBB permeability: Intestinal dysbiosis leads to decreased claudin expression. Inflammation and oxidative stress: The decrease of SCFAs concentration leads to the dysfunction of microglia; the increase of LPS concentration activates microglia, NLRP3 inflammasome and promotes the expression of iNOS. Changes of the production of dopamine: Dysbiosis changes the level of dopamine produced in the gut; the concentration of SCFAs affects the secretion of ghrelin, thus affecting the secretion of dopamine in substantia nigra. Molecular mimicry: Bacterial amyloids may induce immune response to αSyn in human body. SCFAs, short-chain fatty acids; BBB, blood–brain–barrier; LPS, lipopolysaccharide; iNOS, inducible NO synthase.