The Gut-Brain Axis and Its Relation to Parkinson's Disease: A Review

Abstract

Parkinson's disease is a chronic neurodegenerative disease characterized by the accumulation of misfolded alpha-synuclein protein (Lewy bodies) in dopaminergic neurons of the substantia nigra and other related circuitry, which contribute to the development of both motor (bradykinesia, tremors, stiffness, abnormal gait) and non-motor symptoms (gastrointestinal issues, urinogenital complications, olfaction dysfunction, cognitive impairment). Despite tremendous progress in the field, the exact pathways and mechanisms responsible for the initiation and progression of this disease remain unclear. However, recent research suggests a potential relationship between the commensal gut bacteria and the brain capable of influencing neurodevelopment, brain function and health. This bidirectional communication is often referred to as the microbiome-gut-brain axis. Accumulating evidence suggests that the onset of non-motor symptoms, such as gastrointestinal manifestations, often precede the onset of motor symptoms and disease diagnosis, lending support to the potential role that the microbiome-gut-brain axis might play in the underlying pathological mechanisms of Parkinson's disease. This review will provide an overview of and critically discuss the current knowledge of the relationship between the gut microbiota and Parkinson's disease. We will discuss the role of α-synuclein in non-motor disease pathology, proposed pathways constituting the connection between the gut microbiome and the brain, existing evidence related to pre- and probiotic interventions. Finally, we will highlight the potential opportunity for the development of novel preventative measures and therapeutic options that could target the microbiome-gut-brain axis in the context of Parkinson's disease.

Keywords: Parkinson’s disease; alpha-synuclein; dysbiosis; gut–brain axis; microbiome.

FIGURE 1

Overview of the gut–brain axis in Parkinson’s disease. Visual overview of the proposed microbiome–gut–brain axis in Parkinson’s disease. (A) LPS and other bacterial metabolites may be able to enter the brain across the blood–brain barrier (BBB) and may elicit release of various chemokines/cytokines that promote an inflammatory response in Parkinson’s disease. (B) Microbes in the gut lumen can promote inflammatory pathways and cause damage to enterocytes which may lead to compromised gut epithelial barrier integrity (“leaky gut”). (C) Bacterial metabolites, such as LPS, can translocate from the gut lumen to the bloodstream across the compromised gut barrier and cause possible systemic and neuroinflammation in the brain. (D) Misfolded α-synuclein may be induced by microbes at the intersection of the gut lumen and ENS and may be propagated to neurons in the brain through the vagus nerve. (E) Probiotic interventions are thought to reverse dysbiosis through altering the composition of the microbiome. This change is also purported to result in reduction of inflammation and improvement of gut epithelial barrier integrity, thereby preventing or reducing microbial translocation. This figure was created with BioRender.com.