The Gut-Brain Connection and Parkinson’s Disease Progression
Published: March 1, 2024

 By: K. Strachan – U-Turn Parkinson’s Member

 My medical past is liberally pockmarked with various gastrointestinal issues:

  • A massive Giardia – Beaver Fever – a parasite of my intestine in my early thirties (That’s what helping a grad student studying beaver populations in Northern Manitoba gets you!)
  • Hospitalized at least half a dozen times with devastatingly painful intestinal cramping, very high fevers, and other flu-like distresses. Each incident a torturous, usually extended, ordeal!
  • Emergency Surgeons at multiple hospitals across the country have at various times had me prepped for emergency appendectomies (yes more than once), a twisted bowels removal procedure, scans for cancerous growths and the like… But to date I still have my appendix and all my intestines, and I’m cancer free as well.
  • I’ve also been told I’ve had Spinal Meningitis that would kill or paralyze me, a number of terrible influenza, I.B.D., I.B.S, severe constipation and intestinal polyps among an assortment of other medical concerns.

Clearly, my past and current medical state is like an effluent engorged river particularly as it concerns bowel and intestinal problems! These ongoing issues are significant. Pankaj J. Pasricha, gastroenterologist, and his colleagues demonstrated that four gastrointestinal issues in particular — constipation, dysphagia (difficulty swallowing), gastroparesis (delayed stomach emptying) and irritable bowel syndrome without diarrhea — increase the risk of being diagnosed with Parkinson’s. I am currently impacted by 3 of the 4 issues and have been for decades.

When I was formally diagnosed with Parkinson’s disease 4 years ago on November 25, 2020, my movement specialist thoroughly explored my medical history spanning decades. His thoughts based on his assessment was that I not only had Parkinson’s disease, but that I’ve likely had it since my early thirties. My gut health was a massive red flag.

As I explored the particulars of my newly diagnosed condition, I discovered that there was a tremendous body of research and increased interest in exploring the gut-brain connection in Parkinson’s disease: an attempt at uncovering a link between gut health and disease progression! The gut-brain connection in Parkinson’s disease (PD) is an intriguing and rapidly evolving area of research that delves into the complex interactions between the
gastrointestinal system and the central nervous system.

Here are some of the key take-aways that have emerged:

1. Alpha-Synuclein Pathology: Alpha-synuclein is a protein commonly connected with PD. Large collections of this protein are a hallmark of PD and are found in the brain. Intriguingly, these collections of proteins are also observed in the enteric nervous system (ENS) of the gut. Research suggests that alpha-synuclein pathology might originate in the gut and travel to the brain via the vagus nerve, a direct neural link between the gut and the brain.

The ‘Gut-First’ Hypothesis

What is known as the “gut-first” — as opposed to “brain-first” — hypothesis states that Parkinson’s begins as abnormal proteins in the nerves of the gastrointestinal tract. While normal proteins fold into a specific three-dimensional shape, misfolded proteins fail to achieve this form. Misfolded proteins, found excessively in the post-mortem brains of patients with Parkinson’s accumulate into large, toxic clumps that disrupt nerve cell function.

“According to the hypothesis, the inciting agent — this misfolded protein — starts in the nerves of the gut wall and ascends to the brain, causing those pathological changes that lead to Parkinson’s,” said Pankaj J. Pasricha, gastroenterologist and chair of internal medicine at the Mayo Clinic. “If we can prove that the disease is progressing from the gut to the brain, then we can start thinking about early prevention.”

2. Gut Microbiota: The gut microbiome, the trillions of microbes residing in our intestines, appears to play a significant role in PD. Studies have shown differences in the composition of the gut microbiota between individuals with PD and healthy controls. It has been consistently demonstrated that patients with PD show decreased Lachnospiraceae and Prevotellaceae abundances and increased Verrucomicrobiaceae and Lactobacillaceae abundances. These changes in gut bacteria can influence immune responses, produce neurotoxic metabolites, or generate short-chain fatty acids that affect brain function.

3. Gastrointestinal Symptoms: Patients with PD often experience gastrointestinal symptoms long before the onset of motor symptoms. In fact, Gastrointestinal dysfunction is the main early non-motor symptom of PD. Up to 80% of patients with PD may experience gastrointestinal problems. These include constipation, which is particularly common in PD and occurs years or even decades before the motor symptoms of PD appear, gastric emptying delays, and changes in gut permeability. These symptoms provide early clues about the involvement of the gut in PD and may be crucial for early diagnosis and intervention.

4. Inflammation and Immune Response: Chronic inflammation in the gut can lead to an immune response that may contribute to neurodegeneration in PD. Pro-inflammatory cytokines produced in the gut can travel through the bloodstream to the brain, potentially triggering neuroinflammatory processes.

5. Environmental Factors and Toxins: Exposure to environmental toxins, such as pesticides, might initiate PD pathology in the gut. The gut epithelium, which can be compromised due to various factors, might allow these toxins to enter the body more easily, thereby contributing to the onset and progression of PD.

6. Therapeutic Implications: Understanding the gut-brain axis in PD can open up new avenues for treatment and management. This includes the use of probiotics, prebiotics, dietary modifications, and gut-targeted therapies to modify the course of the disease.

In summary, the gut-brain connection in Parkinson’s Disease represents a shift in understanding this complex neurodegenerative disorder. As research progresses, it is likely that this connection will become increasingly important in developing preventative and therapeutic strategies for Parkinson’s Disease.

Written by K.Strachan.




4. Study uncovers a strong link between gut bacteria and development of Parkinson’s