Expert Briefing: The Gut–Brain Connection: How Digestive Health Affects Parkinson’s

Scientists often refer to the gut as the second brain. It controls our immune, metabolic and nervous systems and has the power to shape our behavior and health. Researchers are learning that what happens in the gastrointestinal (GI) tract may have an impact on the brain, including in Parkinson’s disease (PD). Learn about the latest research on the gut–brain connection, what it could mean for understanding Parkinson’s and how caring for your gut may help manage symptoms.

This article is based on an Expert Briefing hosted by Bianca R. Palushaj, MD, Clinical Assistant Professor in the Department of Neurology and Neurological Sciences Division of Movement Disorders at Stanford Medicine, a Parkinson's Foundation Center of Excellence.

Clues that Parkinson’s May Start in the Gut

Gut issues are common in Parkinson’s. Researchers estimate anywhere from 60 to 90% of people with PD experience constipation. Along with constipation, heartburn, trouble swallowing and other GI symptoms can start years, or even decades, before movement symptoms.

Gut trouble often occurs throughout the GI tract. Types of GI dysfunction in PD can include:

• Swallowing issues 
• Dry mouth
• Drooling
• Gum and bone infection in the mouth
• Increased tooth decay and cavities
• Slowing of the digestion system
• Irritation and breakdown of the gut’s protective lining
• Bacterial overgrowth
• Difficulty emptying the bowels
• Trouble coordinating bladder and bowel muscles (this can lead to frequent bathroom trips or pain, pressure and straining if the pelvic floor fails to let stool exit)

Gut changes in Parkinson’s can also impact levodopa absorption, meaning medication may wear off faster or never seem to take effect at all.

Exploring the Gut-Brain Connection 

Researchers are looking more closely at how the gut and brain interact, particularly at the enteric nervous system — a network rich with nerve cells in the walls of the GI tract that allow the gut to run largely on its own, independent of the brain. 

Alpha-synuclein is a protein that helps cells communicate. In Parkinson’s, the protein misfolds and forms into Lewy body clumps, which are commonly found in the nerve cells of the GI tract of people with Parkinson’s. Widespread distribution of these clumps throughout the intestines is linked to worse symptoms. These abnormal proteins can also be found in a person’s digestive tract years before they develop Parkinson’s movement symptoms.

What triggers alpha-synuclein to misfold in the gut?

Throughout life, diet, pollutants, infections, stress and other factors affect everyone differently. One hypothesis suggests that in some people, Parkinson’s may begin with inflammation in the gut. Bacteria, environmental toxins or other triggers could set off gut inflammation, potentially pushing Parkinson's along two main routes: 

1. The protein route: Inflammation causes gut nerve cells to make more alpha-synuclein and encourages it to misfold and clump. Those clumps can travel up the vagus nerve — the gut-brain highway — where they can enter the brain.
2. The inflammation route: Gut inflammation can make the gut lining leaky, allowing oxygen in and bacterial byproducts out. This can let oxygen into the gut, promoting harmful bacteria and allowing bacterial byproducts and other inflammatory molecules out and into the bloodstream. This can lead to inflammation that can disrupt the blood–brain barrier. Brain inflammation may contribute to nerve-cell loss. The process can become a vicious cycle, damaging healthy gut microbes and making the gut more vulnerable to future triggers.

More on the Possible PD-Gut Inflammation Link

The gut microbiome is a community of trillions of microorganisms that live along the GI tract. It is powerful — 70% of our immune system resides there. Changes in the gut can influence inflammation, medication processing and more. The gut microbiome performs many functions critical to overall health, including:

• Breaking down and harvesting energy from food.
• Introducing vitamins the body can't make, such as B and K. 
• Transforming food into compounds such as short-chain fatty acids that are critical to good health.
• Producing neurotransmitters: some gut bacteria can synthesize dopamine or its precursor, while others can metabolize levodopa, impacting its absorption and effectiveness in some people.

Immune and nerve cells in the gut wall are constantly monitoring and responding to what's happening inside the gut. These cells are exposed to bacterial byproducts in things we eat and inflammatory signals. 

A thick mucus layer protects the gut’s nervous and immune systems. When we don’t get enough fiber, microbes can eat the protective mucus layer instead, which thins the protective barrier, allowing bacteria in, triggering inflammation.

Studies in animal models suggest that something about the gut microbiome may cause alpha-synuclein to clump. Genetically engineered mice without one develop fewer alpha-synuclein clumps in the brain. than mice with normal gut bacteria. 

Taking A Closer Look at Natural Amyloid Proteins

Alpha-synuclein is an amyloid protein, which means it can misfold. Thousands of other gut bacteria, such as E. coli, produce amyloid proteins. One example, called curli, looks like the amyloid proteins in Parkinson’s (alpha-synuclein) and Alzheimer's disease (amyloid beta). 

The resemblance is close enough where the immune system may not be able to tell the difference between them. There's preclinical (not yet tested in humans) evidence that curli can act as a seed: when it contacts normal human alpha-synuclein, it may promote misfolding and clumping. In mouse models, exposure to curli-producing E. coli worsened alpha-synuclein pathology and movement problems.

What do we know about the gut microbiome and Parkinson's disease?

Many bacterial species can perform similar functions in the gut. Scientists are working to understand what different bacteria do, which metabolites they produce and what a healthy gut microbiome looks like.

Studies have found differences in the gut microbiome in people with Parkinson’s compared to people without the disease. People with Parkinson's often have fewer short-chain fatty acids. This decrease can drive an inflammatory response that increases oxygen inside the gut and drives the growth of harmful bacteria.

Throughout our lives, diet, environmental exposures, stress and infections can increase inflammation and the risk of chronic disease. Dietary fiber feeds gut bacteria that produce short-chain fatty acids, which may help reduce inflammation, thus protecting the body.

The gut environment in Parkinson’s may become less supportive of beneficial bacteria because of inflammation, damage to the gut barrier and dietary changes. 

Swallowing problems, constipation, and other digestive PD symptoms can affect nutrition and quality of life. Bring these challenges up to your healthcare team to explore ways to support gut health and ease symptoms.

Steps Toward a Healthy Gut

Scientists are exploring sampling capsules (a device that can be swallowed to collect samples of gut bacteria) as a new research tool. New potential future therapies also include:

• Fecal microbiota transplantation 
• Microbiome-targeted drugs to modify gut bacteria
• Vagus-nerve stimulation for its potential to reduce inflammation in PD)

While research on the safety and effectiveness of these potential treatments is still developing, there are already proven ways to boost gut health. 

A fiber-rich diet can be broken down by multiple types of gut bacteria, encouraging new, healthy bacteria to grow in the gut. Here’s how to start:

• Aim for a varied diet that includes fiber-rich and fermented foods and stay well hydrated. Ask your doctor what daily fiber target is appropriate for you. Increase fiber slowly, especially if you experience delayed stomach emptying (gastroparesis), small intestinal bacterial overgrowth (SIBO) or other gut issues.
• Fermented foods that contain live bacteria may help support gut health and reduce inflammation. Examples include yogurt, kefir, fermented cottage cheese, kimchi and other fermented vegetables, vegetable brine drinks and kombucha tea.
• Get moving. Exercise increases good-for-you, short-chain fatty acids.
• Minimize ultra-processed foods, food additives and pesticides, when possible. Wash all produce.
• If you are considering dietary supplements, try whole foods instead if possible. While psyllium can help increase dietary fiber, there is limited evidence of benefits for probiotic supplements. 

Tackling Constipation

Constipation has different causes and different treatments:

• Slow-transit constipation may respond to hydration, fiber, laxatives and other medications.
• Dyssynergic defecation is a pelvic-floor coordination problem. It is treated with pelvic-floor therapy and biofeedback, rather than relying on laxatives alone.

Foods and supplements may help, including:

• Prunes, pears, apples, kiwi and other fruits.
• Polyethylene glycol 3350 (brand name MiraLAX) or magnesium oxide. Check with your doctor before using magnesium, especially if you have kidney disease.
• Senna and bisacodyl (Dulcolax) stimulate the bowel and may be useful when needed.
• Aloe vera is considered a rescue or short-term only supplement.

Other constipation strategies include staying active, scheduling regular toilet times, sitting with your knees above your hips and using the restroom during a reliable medication “on” period. Talk with your doctor about which strategies are appropriate for you.

Things to Keep in Mind

Protein and large meals can delay or reduce levodopa absorption in some people. Talk to your doctor about possibly taking levodopa 30 minutes before or one hour after meals. 

A registered dietitian can help you plan menus that account for your needs and medication timing.

Learn More

Explore our resources about the gut-brain connection in Parkinson’s:

• Read The Gut-Brain Connection: Why Diet Can Help Parkinson’s Symptoms & Brain Health.
• Listen to our podcast to explore Nutrition Tips or Eating Well with Parkinson’s.
• Learn more about what research has uncovered: Study Finds Potential Link Between Parkinson's and Gut Health.
• Read our Constipation Fact Sheet. 
• Discover why prioritizing healthy eating matters with the Parkinson’s Foundation’s Learning Lab Course: Nutrition: Yours and Theirs.