The Role of the Gut in Parkinsons Disease

Abstract

Parkinsons disease (PD) is the second most common neurodegenerative condition worldwide and is characterized by dopamine deficiency and Lewy body deposition composed of abnormal alpha-synuclein in the surviving neurons of the substantia nigra [1,2]. While the motor features of PD are well documented its pre-motor features are increasingly becoming recognized with constipation the most frequently reported. This is often associated with small gut intestinal bacterial overgrowth and Helicobacter pylori which are known to worsen motor symptoms [3]. It is because of this the possible role of the gut in PD pathogenesis is being investigated as described by Braaks Hypothesis [4]. Within the gut lies the microbiome, home to an estimated 100-trillion bacteria, two-thirds of which are unique to each individual and are inherited maternally at birth [2,3]. While 50% to 60% of these bacterial species are yet to be cultured it was thought that their function was to aid digestion and vitamin synthesis however in recent years the existence of a bidirectional gut-brain axis mediated by the vagus nerve which incorporates autonomic/enteric nervous systems and overlapping endocrine/immune systems has been recognized [2,3]. This relationship is evident by the identification of cholinergic anti-inflammatory pathways in the CNS to the gut and the role of gut bacteria in microglia maturation [5,6]. The enteric nervous system consists contains a significant proportion of dopaminergic neurons [6]. In addition, half of the body’s dopamine production is made by gut bacteria with gut Lewybody burden correlating with vagal nerve distribution [3,7].