The Gut-Brain Connection in Parkinson’s Disease

04/16/2025

Research links upper GI inflammation to Parkinson’s disease. Individuals at risk should consult neurologists and gastroenterologists for early detection and care.

By Paul Wright, MD, Senior Vice President and System Chair of the Neuroscience Institute and Steven Gorelick, MD, Senior Vice President and System Chair of the Digestive Health Institute, Nuvance Health

It might sound surprising, but recent research suggests your gut could play a bigger role in brain health than we once thought — especially when it comes to Parkinson’s disease. Understanding the link between these two systems is more important than ever; gastrointestinal (GI) issues like acid reflux and peptic ulcers are common, and Parkinson’s disease affects about 1 million people in the U.S. — a number expected to rise.

The gut-first hypothesis and Parkinson’s disease

The gut-brain connection in Parkinson’s disease (PD) is no longer just a theoretical framework. Recent research published in JAMA Network Open, a peer-reviewed medical journal, highlighted how mucosal damage of the lining of the GI tract can be a risk factor for the later development of PD. The study’s long follow-up period of nearly 15 years adds further weight to the hypothesis that digestive tract health plays a role in Parkinson’s disease progression.

The study observed that individuals with the below types of upper GI mucosal damage were 76% more likely to develop PD than those without damage. These findings emphasize a potential gut-first pathway for PD, where changes in the gut precede the neurodegenerative changes typically associated with Parkinson’s.

Mucosal damage of the gastrointestinal tract can happen for various reasons, including:

Esophagitis is inflammation of the esophagus (the tube that connects the mouth and stomach), often caused by chronic acid reflux, called gastroesophageal reflux disease (GERD).

Erosive gastritis occurs when the stomach lining is damaged. Helicobacter pylori (H. pylori) — a bacterial infection — or chronic use of certain medications, like NSAIDs (nonsteroidal anti-inflammatory drugs) can damage the stomach lining and cause peptic ulcers (sores).

These conditions are common among Americans. An ultra-processed diet, stress, smoking and excessive alcohol consumption are risk factors for these conditions.

How would you know if you have these digestive health conditions? If you have persistent symptoms that are not improving with lifestyle changes, like diet, or medications, your doctor may recommend you have an esophagogastroduodenoscopy or an upper endoscopy. During an upper endoscopy, a gastroenterologist inserts an endoscope, a narrow, flexible tube with a camera and light at the end of it, into your mouth and down to see inside your esophagus, stomach and top part of the small intestine.

What is Parkinson’s disease?

Parkinson’s disease is a movement disorder affecting the brain and nervous system. It causes involuntary muscle contractions throughout the body. As a neurodegenerative disease, symptoms worsen over time and there is no cure. However, early diagnosis and intervention may help slow progression of the symptoms.

Historically, Parkinson’s disease has been viewed as a disorder originating solely in the brain, with hallmark motor symptoms such as tremors and muscle rigidity. However, non-motor symptoms, such as constipation, often manifest years before motor symptoms, suggesting the disease may begin in the gut for a subset of people.

Learn more about Parkinson’s Disease and Movement Disorders at the Nuvance Health Neuroscience Institute.

The gut-brain connection in Parkinson’s disease and the role of upper gastrointestinal health

From a gastroenterological standpoint, this research is a call for increased vigilance in individuals with conditions that damage the upper GI tract, involving the esophagus, stomach and first part of the small intestine, called the duodenum.

The study specifically looked at GERD, H. pylori infections and peptic ulcer disease, which we know cause mucosal damage to the digestive tract. The research found GERD and H. pylori infections were associated with a marked increase in the risk of developing Parkinson’s disease among those with mucosal damage.

The potential implication for digestive health is profound. Regular screening and proactive management of GI conditions could provide an early warning system for people at risk of neurodegenerative diseases like PD.

What are risk factors for Parkinson’s disease?

So, who may be at risk of developing Parkinson’s disease? We believe your genes play a role. Meaning, if a first degree relative (parent, sibling) has Parkinson’s disease, you may have elevated risk of developing it.

Age is a risk factor for PD, with most people developing the movement disorder after age 60. Gender may also play a role, with men more likely to develop PD than women.

The role of the gut microbiome in Parkinson’s disease

Beyond mucosal damage, the gut microbiome — the trillions of microorganisms that live in our digestive tract — is emerging as a key player in the gut-brain connection. The gut microbiome is known to influence various aspects of health, including immune function, metabolism, mood and cognition. In the context of Parkinson’s disease, alterations in the gut microbiome may contribute to the onset and progression of neurodegenerative changes.

Recent studies have shown that people with Parkinson’s disease often have distinct changes in their gut microbiome composition compared to those who don’t have the movement disorder. These alterations may lead to increased intestinal permeability (“leaky gut”) and systemic inflammation, potentially triggering or exacerbating neuroinflammatory processes in the brain. Moreover, certain gut bacteria can produce metabolites (molecules involved in metabolism) that affect the nervous system, such as short-chain fatty acids, which have been shown to influence brain health.

The gut microbiome may also play a role in the misfolding of alpha-synuclein, the protein that aggregates in the brains of Parkinson’s patients. Some researchers hypothesize that abnormal gut microbiota may promote the formation of misfolded alpha-synuclein in the gut, which then travels to the brain via the vagus nerve, contributing to PD.

These findings highlight the need for a broader focus on gut health, not only in the context of mucosal damage but also in maintaining a balanced and diverse microbiome. The future of Parkinson’s disease research and treatment may well involve strategies aimed at restoring gut microbial balance — whether through diet, probiotics or even microbiome transplantation.

A holistic approach to digestive and neurological health

As we advance our understanding of PD, it becomes clear a holistic approach to identifying those at increased risk is needed.

If you have a family history of Parkinson’s disease or a history of GERD, stomach ulcers or other upper digestive tract conditions, please work with your gastroenterologist to manage these conditions. If you also have a family history of Parkinson’s disease, tell your doctor.

GI health is a critical piece of the broader puzzle of Parkinson’s disease. Gastroenterologists and neurologists can open new avenues for early detection and treatment of neurodegenerative conditions. By collaborating, we can ensure people with significant mucosal damage are monitored more closely for signs of PD, facilitating earlier interventions to potentially mitigate the disease’s progression.

But more evidence-based research is necessary to better establish the connection and pathways for treatment and evolve the standard of care, if necessary. It’s currently not standard of care to perform upper endoscopy for screenings for gastrointestinal inflammation.

At the Neuroscience Institute, we are committed to pushing the boundaries of interdisciplinary collaboration between neurology and gastroenterology. The Digestive Health Institute shares this commitment, working to help people stay well through healthy lifestyle education and expert management of chronic digestive conditions like GERD.

The bottom line: A new study showed a 76% increased risk of Parkinson’s disease in people with significant upper GI mucosal damage in the digestive tract. The gut-first hypothesis suggests that Parkinson’s may begin in the gut before affecting the brain. Common GI conditions like GERD and H. pylori infections may signal elevated Parkinson’s risk, and the gut microbiome could influence the development and progression of PD.

If you have upper GI conditions, please work with you gastroenterologist to manage symptoms and follow a healthy diet and exercise — especially if you have a family history of Parkinson’s disease.

Gastroenterologists and neurologists should work together to better understand and manage PD. While promising, this research is just the beginning — more studies are needed to guide future care.

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