Damage to upper GI tract lining tied to 76% higher Parkinson’s risk
Gut symptoms like constipation, nausea can precede motor symptoms by years
People with a history of damage to the lining of the upper gastrointestinal (GI) tract, called the gastrointestinal mucosa, had an elevated risk of developing Parkinson’s disease in a recent U.S. study.
“We found that a history of upper GI mucosal damage was associated with a 76% greater risk of subsequently developing Parkinson’s disease, highlighting the necessity for heightened monitoring of these patients,” Trisha S. Pasricha, MD, a physician and researcher at Beth Israel Deaconess Medical Center, instructor at Harvard Medical School, and the study’s senior author, said in a press release. “Understanding the path from mucosal damage to Parkinson’s disease pathology may prove crucial to early recognition of risk as well as potential intervention.”
The study, “Upper Gastrointestinal Mucosal Damage and Subsequent Risk of Parkinson Disease,” was published in JAMA Network Open.
The hallmark of Parkinson’s disease is a toxic, misfolded version of the alpha-synuclein protein accumulating in the brain. Recent evidence suggests a so-called “gut-first” hypothesis, which indicates these Parkinson’s disease processes actually start in the gut before making their way to the brain.
“People often think about the ways the brain influences the gut, but the gut can exert enormous influence on the brain in ways we are still only beginning to understand,” Pasricha said.
Lending support to the gut-first theory is that many Parkinson’s patients have GI symptoms such as constipation and nausea for years, sometimes decades, before the first motor symptoms of the neurodegenerative condition arise. The factors that may trigger disease processes in the gut and their eventual spread to the brain, aren’t fully understood, however.
“Our lab has been trying to better illuminate this ‘gut-first’ pathway of Parkinson’s disease because it can open new avenues for early intervention and treatment strategies,” Pasricha said.
One possibility is that mucosal damage in the upper GI tract — the esophagus, stomach, and first part of the small intestine — could trigger inflammation in the gut that spurs the disease. This type of damage, which includes stomach ulcers, commonly arises from nonsteroidal anti-inflammatory medications (NSAIDS) like ibuprofen, from infection with the Helicobacter pylori bacterium, or gastroesophageal reflux disease (GERD), known as acid reflux.
Mucosal damage and link to Parkinson’s
The researchers reviewed information from a large electronic database containing health information from urban academic centers, outpatient clinics, and community hospitals in the Boston area to establish a link between upper GI tract damage and later developing Parkinson’s.
They selected 11,293 people who underwent an upper endoscopy, a type of imaging procedure to find problems in the upper GI tract, between 2000 and 2005. Of them, 2,338 people were found to have mucosal damage and 8,955 were not. Those with mucosal damage had higher rates of constipation, swallowing dysfunction, called dysphagia, H. pylori infections, and an overall higher burden of coexisting conditions than those without it.
Participants were followed through July 2023 to monitor for Parkinson’s disease. Among those with mucosal damage, 2.2% were diagnosed with Parkinson’s, whereas 0.5% of those without mucosal damage developed the condition.
When people with mucosal damage were matched in a 1:3 ratio to people without mucosal damage based on influencing factors such as age at the time of the endoscopy, sex, race, co-occurring diseases, and other GI symptoms, researchers found that the risk of developing Parkinson’s was 76% higher among those with mucosal damage. Parkinson’s was diagnosed at a mean age of 72.7 and a mean of 14.2 years after mucosal damage was detected.
Other factors associated with an increased risk of developing Parkinson’s included older age, a history of constipation, and dysphagia. Asian, Black, and other race groups were at a lower risk of Parkinson’s relative to white populations.
Among those with upper GI mucosal damage, having GERD or being positive for H. pylori infection were associated with significantly higher odds of developing Parkinson’s. These links weren’t seen in the patients without mucosal damage.
Given this difference, it’s possible the link between mucosal damage and Parkinson’s, “may not be contingent on one isolated abnormality, but rather a cumulative effect of multiple GI inflammatory insults,” wrote the researchers, who said the findings underscore the importance of monitoring patients with upper GI mucosal damage for signs of Parkinson’s and show better gut biomarkers of Parkinson’s disease are needed.
“Timely detection and treatment of H. pylori infection, along with [mucosal damage] management, may prove crucial to early recognition of risk of and potentially intervention against [Parkinson’s disease],” they wrote.
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