How Might GI Mucosal Damage Increase Parkinson’s Risk by 76% Per Recent Study?

Does New Research Show Parkinson’s Disease Actually Starts in the Gut Not Brain?

New JAMA Network Open research by Subhash Kulkarni reveals gut mucosal damage from ulcers raises Parkinson’s risk 76% over 15 years, supporting Heiko Braak’s gut-first hypothesis where misfolded alpha-synuclein travels via vagus nerve from GI tract to brain.

Learn how doctors should monitor GI patients for early Parkinson’s detection and explore alpha-synuclein prevention strategies detailed in the study’s full implications ahead.

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New medical research suggests that Parkinson’s disease may originate in the gut — and not in the brain as many researchers believe. According to a new study, damage to the mucous lining of the gastrointestinal tract is associated with a much higher risk of developing Parkinson’s. Science journalist Meeri Kim interviewed study author Subhash Kulkarni in the Washington Post about the main findings and steps health care providers could potentially take to better treat patients suffering from this neurodegenerative disease through early detection.

Take-Aways

• New research suggests that mucosal damage to the gastrointestinal lining may significantly increase your likelihood of developing Parkinson’s.
• When proteins in your GI tract “misfold,” they can become toxic, disrupting bodily cell functions.
• Understanding risk factors could help health care practitioners detect Parkinson’s and mitigate its symptoms early on.

Summary

New research suggests that mucosal damage to the gastrointestinal lining may significantly increase your likelihood of developing Parkinson’s.

Scientists have long believed that Parkinson’s disease starts in the brain and then spreads throughout the body. New research, however, suggests it may actually originate in the gut. The first person to propose this “gut-first” hypothesis in 2003 was German anatomist Heiko Braak. A new study helps quell existing skepticism among proponents of the more widely accepted “brain-first” hypothesis. Subhash Kulkarni — an assistant professor at Beth Israel Deaconess Medical Center and an author of the study, published in JAMA Network Open — explains that rather than being a “top-down” disease originating in the brain, Parkinson’s may actually be a “bottom-up” disease, as many patients he and his colleagues observed displayed gastrointestinal (GI) conditions.

“Kulkarni and his colleagues found that people with upper gastrointestinal conditions — in particular, ulcers or other types of damage to the lining of the esophagus, stomach, or upper part of the small intestine — were far more likely to develop Parkinson’s disease later in life.”

Trisha Pasricha, the senior study lead, and her colleagues conducted an analysis of 9,350 people with no Parkinson’s history. Between 2000 and 2005, these 50- to 64-year-old patients had all undergone an upper endoscopy with biopsy — a procedure in which tissue samples are taken from the upper part of the digestive system. Those whose samples revealed damage to the mucous lining of their GI tract were 76% more likely to develop Parkinson’s disease during an average follow-up period of 15 years. In fact, many of the patients who developed Parkinson’s didn’t receive a diagnosis until 14.2 years after their earlier upper endoscopies. The correlation between gut damage and Parkinson’s is significant because future patients with gastrointestinal issues, such as ulcers, could potentially take steps to lessen the symptoms of the neurodegenerative disease, such as the decline of motor function.

When proteins in your GI tract “misfold,” they can become toxic, disrupting bodily cell functions.

According to the emerging gut-first hypothesis, Parkinson’s begins with “misfolded” proteins in the GI tract’s nerves. In order for proteins to assist in performing bodily functions, they form three-dimensional folded structures. However, when proteins misfold, they can trigger a chain reaction in which neighboring proteins also fail to fold properly, causing a build-up of toxic proteins that prevent your organs and tissues from functioning properly. People who suffer from Parkinson’s appear to have a misfolded protein called alpha-synuclein. This protein travels through the body via the vagus nerve, which acts as a “superhighway” connecting the brain and the gut.

“A neuronal protein called alpha-synuclein is the culprit in Parkinson’s disease, and a diagnosis is typically confirmed by the discovery of alpha-synuclein pathology in the post-mortem brain.”

The study’s findings suggest that a damaged gut lining might cause the initial misfolding, leading to an “aberrant deposition of alpha-synuclein in the mucosal tissue.” Research conducted via autopsies reveals that misfolded alpha-synuclein is more present in the GI tract of people suffering from Parkinson’s than in control patients, strengthening the correlation between GI damage and Parkinson’s. In fact, in mice, researchers found that severing the vagus nerve prevents the mice from developing symptoms, such as cognitive decline, associated with Parkinson’s.

Understanding risk factors could help health care practitioners detect Parkinson’s and mitigate its symptoms early on.

If you have mucosal damage in your GI tract, Kulkarni urges you to remain calm, as an increased risk or association doesn’t automatically equate with developing the disease: “There is reason for caution, but there is no reason for panic. We are not saying that every person who has mucosal damage is going to develop Parkinson’s.” Researchers are, however, recommending that doctors monitor patients more closely who display mucosal damage, and give patients suffering from conditions that could cause this damage, such as peptic ulcer disease, timely care to prevent unnecessary damage.

“Solving the mystery of why some people develop Parkinson’s and others don’t could lead to options for early detection, treatment and hopefully, one day, prevention.”

Currently, estimates show that only 10% of Parkinson’s cases are attributed to a genetic predisposition to developing the disease. The majority of Parkinson’s cases, which have doubled over the past two and a half decades, are labeled ‘sporadic,’ which means the cause remains unknown. More research is needed to better understand the reasons why patients develop Parkinson’s — as the disease is growing faster than any other neurological disorder, including Alzheimer’s.

About the Author

Meeri Kim is a science writer and Washington Post contributor with a PhD in physics from the University of Pennsylvania.