Recent research suggests that Parkinson’s disease, long thought to originate in the brain, may actually start in the gut, reports The Washington Post.
New findings in Parkinson’s disease Photo Shutterstock
Studies show that people with upper gastrointestinal conditions, such as ulcers or other damage to the lining of the esophagus, stomach, or small intestine, have a significantly higher risk of developing Parkinson’s later in life. Also, these gastrointestinal conditions are common among patients with neurodegenerative disorders.
In the past, the term “institutional colon” described bowel conditions commonly found in people living in mental health institutions. In Parkinson’s disease, the entire gastrointestinal tract can be affected, causing symptoms such as constipation, excessive salivation, difficulty swallowing, and delayed stomach emptying. These symptoms can appear up to two decades before motor manifestations such as stiffness or tremors.
“It has long been accepted that Parkinson’s disease starts in the brain and then spreads to the gut, causing gastrointestinal problems,” admits Subhash Kulkarni, study author and assistant professor at Beth Israel Deaconess Medical Center.
But another hypothesis suggests that, in many cases, the disease could start in the intestine and then reach the brain, the specialist also mentions.
The recent study published in JAMA Network Open involved 9,350 patients without a history of Parkinson’s disease who underwent upper endoscopy with biopsies between 2000 and 2005. Mucosal damage—including erosions, tears, or lesions in the lining of the gastrointestinal tract—was associated with a 76% greater risk of developing Parkinson’s disease over a mean follow-up period of 14.9 years.
Damage to the mucosa, often detected before the diagnosis of Parkinson’s
Most significantly, the patients had gastrointestinal problems long before they were diagnosed with Parkinson’s, with an average of 14.2 years between the first detection of mucosal damage and the final diagnosis of Parkinson’s.
Delaram Safarpour, associate professor of neurology at Oregon Health & Science University, recommends careful monitoring of patients with mucosal damage and prompt treatment of conditions that can cause such problems, such as peptic ulcers, esophagitis, and Helicobacter Pylori infection: “It is absolutely necessary to monitor these patients who have a history of mucosal damage at endoscopy. Early detection of Parkinson’s disease would allow doctors to treat these patients before motor symptoms develop, when neuroprotective treatments become available in the future.”.
The new findings support an older hypothesis
The study supports the hypothesis proposed by German anatomist Heiko Braak in 2003 that Parkinson’s disease may start in the gastrointestinal tract, not the brain. According to this hypothesis, misfolded proteins can spread to the brain via the vagus nerve (a mixed sensory-motor cranial nerve originating in the spinal cord), triggering the characteristic symptoms of Parkinson’s disease.
“When this theory was originally presented, there was much skepticism in the field. But the evidence has been accumulating, and this study is another step toward recognizing that the gastrointestinal tract is a major pathway by which Parkinson’s can start.”also mentions Ted M. Dawson, professor of neurodegenerative diseases at Johns Hopkins University School of Medicine, who was not involved in the study.
The link between the gastrointestinal tract and Parkinson’s
Proteins normally fold into an ordered three-dimensional structure, which is necessary to become biologically functional, the experts explain. Misfolded proteins fail to achieve this correct shape and can in turn cause neighboring proteins to misfold, leading to the formation of toxic aggregates that disrupt the functioning of cells, tissues and organs in the body.
For example, Alzheimer’s disease is characterized by accumulations of beta-amyloid protein in the brain, which form harmful plaques.
In Parkinson’s disease, the neuronal protein called alpha-synuclein is responsible, and the diagnosis is usually confirmed by identifying alpha-synuclein pathology in the post-mortem brain. Several studies suggest that misfolded alpha-synuclein can spread from the gastrointestinal tract to the brain via the vagus nerve, a neural “highway” that connects the two.
People who have had their vagus nerve cut have a lower risk of the disease
For example, people who have had their vagus nerve cut — a state-of-the-art treatment for peptic ulcers — have a lower risk of developing Parkinson’s disease, the researchers noted.
Autopsy studies and research in mice support this theory, showing that misfolded alpha-synuclein injected into the gut can migrate to the brain and cause Parkinson’s-like symptoms. However, sectioning the vagus nerve completely protects mice against these effects.
The alarming increase in the number of Parkinson’s cases
In conclusion, the number of cases of Parkinson’s disease has increased exponentially over the past 25 years, making it the fastest growing neurological disorder worldwide. Although many cases are considered sporadic and do not have a well-defined cause, recent studies suggest that damage to the intestinal lining may play an important role in triggering Parkinson’s disease.
Kulkarni and his team plan to continue research to further explore these changes and their impact on alpha-synuclein. Until these studies are completed, careful monitoring and prompt treatment of gastrointestinal problems remain essential to prevent or manage the risk of Parkinson’s.
