Abstract
Microbiota have increasingly become implicated in predisposition to human diseases, including neurodegenerative disorders such as Parkinson’s disease (PD). Traditionally, a central nervous system (CNS)-centric approach to understanding PD has predominated; however, an association of the gut with PD has existed since Parkinson himself reported the disease. The gut–brain axis refers to the bidirectional communication between the gastrointestinal tract (GIT) and the brain. Gut microbiota dysbiosis, reported in PD patients, may extend this to a microbiota–gut–brain axis. To date, mainly the bacteriome has been investigated. The change in abundance of bacterial products which accompanies dysbiosis is hypothesised to influence PD pathophysiology via multiple mechanisms which broadly centre on inflammation, a cause of alpha-synuclein (a-syn) misfolding. Two main routes are hypothesised by which gut microbiota can influence PD pathophysiology, the neural and humoral routes. The neural route involves a-syn misfolding peripherally in the enteric nerves which can then be transported to the brain via the vagus nerve. The humoral route involves transportation of bacterial products and proinflammatory cytokines from the gut via the circulation which can cause central a-syn misfolding by inducing neuroinflammation. This article will assess whether the current literature supports gut bacteria influencing PD pathophysiology via both routes.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide
Microbiota undoubtedly play a role in PD pathophysiology
PD is primarily considered a disease of old age, despite pathogenesis preceding motor symptoms by years, with dysbiosis conceivably acting to exacerbate inflammation
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide. Primarily consisting of misfolded fibrillar alphasynuclein (a-syn), are PD neuropathological hallmarks. These aggregates [Lewy bodies (LBs) and Lewy neurites (LNs)], are believed to cause the catecholaminergic (CA) and dopaminergic (DA) neuronal loss which manifests as motor dysfunction (parkinsonism). The microorganisms in the gut are involved in gastrointestinal (GI) homoeostasis, such as maintaining the integrity of the gut epithelial barrier (Miraglia and Colla, 2019), and their abnormal colonisation and function (dysbiosis) can lead to peripheral and/or systemic inflammation (Chen et al, 2019) which may facilitate PD pathophysiology by neural and humoral routes. Gastrointestinal symptoms have been shown to precede motor symptoms by Parkinson himself (Parkinson, 2002). Gut microbiota have been implicated since they can aid in host nutrient metabolism and modulate gastrointestinal motility (Miraglia and Colla, 2019)
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call