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“A growing area of interest is in determining whether any symptoms may precede the onset of Parkinson’s Disease…”

Parkinson’s disease (PD) is a progressive neurodegenerative disorder most often presenting with a constellation of symptoms including slowed movements (‘bradykinesia’), resting tremor, rigidity, and difficulty maintaining balance (‘postural instability’). There are many additional symptoms patients may experience including speech changes, cognitive problems, sleep disturbances, depression, swallowing or chewing difficulties, and constipation. A growing area of interest is in determining whether any symptoms may precede the onset of PD, and so far, evidence seems to suggest that gut changes may indeed occur.

“Research suggests a driving factor in the disease is loss of dopamine producing neurons in the brain…”

The underlying pathophysiology of PD is complex, with both genetic and environmental factors likely playing a role. Research suggests a driving factor in the disease is loss of dopamine producing neurons in the brain and the deposition of Lewy bodies (LB) consisting of misfolded proteins called alpha (α) synuclein throughout the central nervous system (CNS) which includes brain and spinal cord. The discovery of α-synuclein depositions also in the enteric nervous system (ENS) of the gut led researcher Braak and his team in 2003 to propose a gut-first theory of PD: the pathology of α-synuclein may begin in the GI tract, which provides an entryway for pathogens and negative environmental factors such as environmental toxins to induce α-synuclein misfolding inside the gut. These misfolded proteins might then access the brain by traveling up the vagus nerve from the ENS. Notably, the vagus nerve carries signals between the brain, heart, and digestive system. A parallel pathway has been postulated starting in the nose and traveling via the olfactory nerve to the brain. Braak’s hypothesis has been debated over the years, but a new study published earlier this year, in August 2023, is the first to systematically investigate the association of gastrointestinal symptoms and diagnoses with development of PD.

“…this is the first study to provide observational evidence that gastroparesis and dysphagia may also precede PD…”

An international team of researchers analyzed electronic health records across 57 US medical centers ultimately including 24,624 PD patients. They retrospectively evaluated the occurrence of 18 common conditions of the GI tract and two interventions (appendectomy and vagus nerve cutting) prior to the development of PD. Unlike earlier studies, researchers not only compared GI involvement in PD to healthy controls, but also to other neurologic conditions including Alzheimer’s disease (AD) and Cerebrovascular diseases (CVD). Four GI conditions: constipation, difficulty swallowing (‘dysphagia’), delayed gastric emptying (‘gastroparesis’), and Irritable bowel syndrome without diarrhea were found to increase the risk of PD development compared to AD, CVD, and healthy controls. The finding of constipation preceding PD has been extensively reported previously, but this is the first study to provide observational evidence that gastroparesis and dysphagia may also precede PD. The observation that IBS symptoms may precede PD is questionable and may be related to an overlap of diagnoses for chronic constipation and constipation-predominant IBS.

Since there is currently no cure for Parkinson’s, identifying precursors to the disease may offer opportunities for earlier diagnosis and potential development of targets to slow or prevent progression. Changes in gut health seem to occur prior to the development of PD and more studies investigating various components of this association are currently underway.