ABSTRACT
The cause of Parkinson's disease (PD) is unknown, but environmental factors are purported to influence risk. Interest in PD as a sequel of infection dates back to reports of parkinsonism arising from encephalitis lethargica. The objective of this paper is to review the literature as it relates to infections and changes in microbiome and the genesis of PD. There is evidence to support prior infection with Helicobacter pylori, hepatitis C virus, Malassezia, and Strep pneumonia in association with PD. A large number of studies support an association between changes in commensal bacteria, especially gut bacteria, and PD. Extant literature supports a role for some infections and changes in commensal bacteria in the genesis of PD. Studies support an inflammatory mechanism for this association, but additional research is required for translation of these findings to therapeutic options.
Subject(s)
Gastrointestinal Microbiome , Helicobacter pylori , Microbiota , Parkinson Disease , Humans , Parkinson Disease/microbiologyABSTRACT
Parkinson's disease (PD) is the second most common neurodegenerative disease amongst the middleaged and elderly populations. Several studies have confirmed that the microbiotagutbrain axis (MGBA) serves a key role in the pathogenesis of PD. Changes to the gastrointestinal microbiome (GM) cause misfolding and abnormal aggregation of αsynuclein (αsyn) in the intestine. Abnormal αsyn is not eliminated via physiological mechanisms and is transported into the central nervous system (CNS) via the vagus nerve. The abnormal levels of αsyn aggregate in the substantia nigra pars compacta, not only leading to the formation of eosinophilic Lewis Bodies in the cytoplasm and mitochondrial dysfunction in dopaminergic (DA) neurons, but also leading to the stimulation of an inflammatory response in the microglia. These pathological changes result in an increase in oxidative stress (OS), which triggers nerve cell apoptosis, a characteristic of PD. This increase in OS further oxidizes and intensifies abnormal aggregation of αsyn, eventually forming a positive feedback loop. The present review discusses the abnormal accumulation of αsyn in the intestine caused by the GM changes and the increased levels of αsyn transport to the CNS via the MGBA, resulting in the loss of DA neurons and an increase in the inflammatory response of microglial cells in the brain of patients with PD. In addition, relevant clinical therapeutic strategies for improving the GM and reducing αsyn accumulation to relieve the symptoms and progression of PD are described.