Implications of Gut Microbiome Dysbiosis in Parkinson's Disease: A Literature Review.

Objective: To review the evidence showing an association between gut microbiome (GM) dysbiosis and Parkinson’s disease (PD), with an emphasis on the mechanisms by which GM dysbiosis may be involved in PD pathophysiology. Background: The GM plays an important role in the development and homeostasis of different body systems, including the central nervous system (CNS) via the gut-brain axis. Autopsy-based studies have demonstrated that α-synucleinopathy is not limited to the CNS but also affects the enteric nervous system (ENS) of PD patients. Moreover, gastrointestinal symptoms of PD predate motor symptoms. Accordingly, studies have looked at GM changes in PD, the consequences of these changes and their possible implications in PD pathophysiology. Design/Methods: A literature review was conducted using PubMed to identify studies that evaluated the differences between GM of PD patients and of healthy individuals. Also, studies that investigated the mechanisms by which GM changes might trigger or influence PD pathogenesis were reviewed. Results: There are significant changes in GM of PD patients as compared to that of healthy individuals, which cause decreased production of neuroprotective factors such as short-chain fatty acids (SCFA) and ghrelin. Such changes also increase the release of bacterial neurotoxins including lipopolysaccharide, epoxomicin, and β-N-methylamino-L-alanine into the systemic circulation which might potentiate nigral dopaminergic degeneration given the disrupted blood-brain barrier in PD. Conclusions: GM changes might be related to the underlying pathophysiology of PD via different mechanisms. A better understanding of the consequences of GM changes, especially those taking place in the ENS and CNS, can help identify the key factors triggering α-synucleinopathy, and provide potential targets for clinical trials to test potential disease-modifying agents for PD including SCFA, probiotics, Tumor Necrosis Factor-alpha antagonists and recombinant ghrelin. Disclosure: Dr. Elfil has nothing to disclose. Dr. Kamel has nothing to disclose. Dr. Kandil has nothing to disclose. Dr. Ahmed has nothing to disclose. Dr. Schaefer has nothing to disclose. Dr. Koo has nothing to disclose.