Damage to gut lining from ulcers, ibuprofen may increase Parkinson's risk

• The exact cause of Parkinson’s is unclear, but experts believe that genetic changes and environmental factors, such as toxins, play a role in increasing a person’s risk of developing the condition.
• More recently, studies have shown that the gut could play a major role in the development of Parkinson’s.
• A new study has suggested that damage to the upper gastrointestinal tract may increase Parkinson’s risk by 76%.

According to the Parkinson’s Foundation , a million people in the U.S. are living with Parkinson’s disease, a number that is expected to rise to 1.2 million by 2030. While age is the most significant risk factor for Parkinson’s disease, around 4% of cases are diagnosed in people under the age of 50.

Experts do not know the exact cause of the condition, but some cases are thought to be hereditary, with specific gene variants leading to Parkinson’s disease. However, most cases appear to result from a combination of genetic and environmental factors.

Increasing evidence is pointing to the role of the gut and the gut microbiome in the development of Parkinson’s disease.

Now, a study has found that people with a history of damage to the upper gastrointestinal (GI) tract from conditions such as gastroesophageal reflux disease (GERD), peptic ulcers , and prolonged use of non-steroidal anti-inflammatory drugs (such as ibuprofen), may have a 76% higher risk of Parkinson’s disease than those without.

The study, led by researchers at Beth Israel Deaconess Medical Center (BIDMC), was published in JAMA Network Open .

Upper GI damage diagnosed by biopsy

The researchers identified 18,305 people who had undergone endoscopy and biopsy investigations between 2000 and 2005. All had no history of Parkinson’s disease.

9,350 participants from the cohort took part in the study. Their mean age at endoscopy was 52.3 years; 55.4% were men, and 73.7% were white, with the remainder Black, Asian, and others.

Of the participants, 2,337 had evidence of mucosal disease (MD) on endoscopy while 7013 did not. The researchers matched people with MD of the upper GI tract by sex, age, and date of endoscopy in a 1:3 ratio with people without this diagnosis.

They followed up with all participants until one of the following endpoints:

• Diagnosis of Parkinson’s disease
• Death
• Loss to follow up, or the final date of follow-up assessments on July 31, 2023.

Parkinson’s more common in people with GI damage

In total, 100 people were diagnosed with Parkinson’s disease during follow-up .

In their nested case-control study, the researchers recorded a Parkinson’s diagnosis in 52 of the 2338 participants with MD (2.2%) and 48 of the 8955 people without MD (0.5%).

Corresponding author, Trisha S. Pasricha, MD, MPH , a neurogastroenterologist and director of Clinical Research at the Institute for Gut-Brain Research at BIDMC explained to Medical News Today :

“In our nested case-control studies, we did look at differences between those who did and did not develop [Parkinson’s] […]— and the main differences were that those with [Parkinson’s] were more likely to have experienced constipation, acid reflux, and dysphagia, which is not surprising, as these have been shown to be associated with Parkinson’s disease in the past.”

Why might there be a gut-brain link?

Studies have suggested that aggregations of a protein — alpha synuclein — in the brain form Lewy bodies, and lead to the loss of dopaminergic neurons, a key feature of Parkinson’s disease. These alpha-synuclein aggregations have also been detected in the gut.

Daniel Truong, MD , neurologist and medical director of the Truong Neuroscience Institute at MemorialCare Orange Coast Medical Center in Fountain Valley, CA and editor-in-chief of the Journal of Clinical Parkinsonism and Related Disorders, who was not involved in the study, explained to Medical News Today how this study adds further evidence for a link:

“The GI tract is known to produce alpha-synuclein, a protein that plays a key role in Parkinson’s. When the gut lining is damaged, it may lead to chronic inflammation or an impaired ability to clear harmful proteins, which could trigger the misfolding of alpha-synuclein.”

“This study provides additional evidence to support the gut-first hypothesis of Parkinson’s disease. By showing a 76% higher risk of developing [Parkinson’s] in individuals with upper GI mucosal damage, it highlights the potential role of gastrointestinal dysfunction in triggering [Parkinson’s]. The findings align with prior research suggesting that misfolded alpha-synuclein proteins may spread from the gut to the brain via the vagus nerve, offering further support for the hypothesis that [Parkinson’s] may originate in the gut.”
— Daniel Truong, MD

Can you reduce your Parkinson’s risk?

Pasricha emphasized that while their study only included people who had sought investigations for gastrointestinal symptoms, we all experience small amounts of damage to the gut lining throughout our lives, and that we don’t yet know how these small amounts of damage might impact Parkinson’s risk.

“I advise my patients, regardless of their risk of any neurological disease, that minimizing NSAIDs, reducing stress, and cutting down alcohol will only help their gut health,” Pasricha told MNT .

“I think this study will help physicians pay closer attention to people who have a history of gastrointestinal issues and keep Parkinson’s on the radar for future, especially if they start to develop other prodromal signs of the disease like trouble sleeping, difficulty swallowing, or changes in sense of smell,” she added.

“Our study found that a specific kind of gut pathology, damage to the lining of the upper gastrointestinal tract, is linked to developing Parkinson’s disease, elevating the risk by 76%. We live in an environment where lots of factors can damage the lining of our guts: taking NSAIDs like ibuprofen, drinking alcohol, stress, or bacteria like H. pylori , for example. These all play an injurious role.”
— Trisha S. Pasricha

Truong echoed her advice:

“There are several lifestyle measures that may help reduce the risk of developing Parkinson’s disease such as exercise, healthy diet, avoid toxin (pesticide, heavy metals) […] studies suggest moderate coffee or tea consumption may lower risk.”

More questions to investigate

Pasricha told MNT that while their study added evidence for a gut-brain connection in Parkinson’s, it also raised further questions:

“Could it be that an injury to the gut lining, as we found in our study, is what triggers that protein to misfold? Or could it be that dopamine is reduced in the guts of people destined to develop Parkinson’s anyway, and this puts them at higher risk of damage to the gut’s lining in the first place?”

“We’re really excited to be investigating those next questions now in my laboratory,” she said .