Gut–Brain Axis: Potential Factors Involved in the Pathogenesis of Parkinson's Disease

With the chances of getting Parkinsons post stroke you just might want your doctor to have a protocol to test your gut microbiota. And then have a protocol to correct any problems.

Parkinson’s Disease May Have Link to Stroke March 2017

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Gut–Brain Axis: Potential Factors Involved in the Pathogenesis of Parkinson's Disease

• ¹Department of Neurology, National Neuroscience Institute, Singapore, Singapore
• ²Department of Neurology, Singapore General Hospital, Singapore, Singapore
• ³Duke NUS Medical School, Singapore, Singapore
• ⁴Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
• ⁵Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore

Increasing evidence suggests an association between gastrointestinal (GI) disorders and susceptibility and progress of Parkinson's disease (PD). Gut–brain axis has been proposed to play important roles in the pathogenesis of PD, though the exact pathophysiologic mechanism has yet to be elucidated. Here, we discuss the common factors involved in both PD and GI disorders, including genes, altered gut microbiota, diet, environmental toxins, and altered mucosal immunity. Large-scale prospective clinical studies are needed to define the exact relationship between dietary factors, microbiome, and genetic factors in PD. Identification of early diagnostic markers and demonstration of the efficacy of diet modulation and regulation of gut microbiome through specific therapeutics can potentially change the treatment paradigm for PD.

Introduction

Parkinson's disease (PD) is a common neurodegenerative disorder affecting 1–2 per 1,000 of the population (1). The incidence rate is generally lower for individuals before the age of 50 years, and it increases steadily with advanced age, peaking at 80 years old (2). The pathological hallmark in PD is the presence of intraneuronal aggregated alpha-synuclein (α-syn), Lewy body formation, and progressive loss of dopaminergic neurons in the substantia nigra compacta (SNc) which leads to the typical clinical symptoms including tremor, rigidity, bradykinesia, and posture instability (1). Current treatment for PD is largely symptomatic.

Although motor symptoms are characteristic in PD, non-motor abnormalities in pre-PD phase are increasingly recognized. Among those, constipation is a prodromal marker in research diagnostic criteria for PD and may be an early manifestation of PD pathophysiology (3–5). The extent of the observed severity of the manifestation, especially the duration preceding PD, is unclear (3). However, several studies associate gastrointestinal (GI) dysfunction as a risk factor for PD development, with an early prevalence of 20% pre-PD diagnosis and 50% of the PD cases post-diagnosis (6, 7). Moreover, the association with GI dysfunction corroborates the well-established Braak's theory that PD initiation might begin in the GI tract, supported by the presence of Lewy body burden in the enteric nervous system (ENS) compared with other body regions and in the central nervous system (CNS) (8, 9). This has led to considerable interests to understand the etiology and presentation of pre-motor symptoms in PD patients. This review highlights the current findings linking pathophysiologic mechanisms between CNS and ENS in PD (Figure 1).

FIGURE 1

Figure 1. Bi-directional interaction between gastrointestinal (GI) tract and central nervous system (CNS). Schematic representation summarizes Braak's model of Parkinson's disease (PD) progression initiated from the GI tract. Changes in GI mucosal immunity, environmental toxins, infection, sleep quality, diet, and genetics modify the gut microflora and induce inflammation, mitochondrial dysfunction, and abnormal protein accumulation. Accumulation of α-syn in the GI tract spread via the vagus nerve to the CNS and leads to dopaminergic neuron degeneration.