The brain and gastrointestinal (GI) system are connected. Resident bacteria, including that in the gut, are unique to every person and a major part of our makeup — bacteria even outnumber cells in the body. The capability of that bacteria, known as the microbiome, is enormous. New research strongly suggests a link between the gut and Parkinson’s disease (PD). Learn what science is finding and discover how you can begin improving gut health today.

This article is based on Parkinson's and the Gut-Brain Connection a Parkinson’s Foundation Expert Briefing webinar presented by Carley Rusch, PhD, RDN, LDN, Medical Science Liaison at Abbott Nutrition.

The Gut’s Microbiome

The gut microbiome spans from the mouth to the colon. It is the network of microorganisms — bacteria, viruses, fungi and more — and their collective genetic material that lives within the intestinal tract. The greatest density and diversity of these microorganisms are found within the colon.

Studies on the relationship between gut bacteria and health date back hundreds of years. Research on the benefits of bacteria in yogurt for treating diarrhea was recorded as early as the 1400s. Today, technology known as high-throughput DNA sequencing gives researchers the power to rapidly identify the thousands of bacterial DNA present in individual stool samples.

Science is uncovering the many ways the gut microbiome can influence brain health, body function and overall wellbeing. It can even impact how the body processes oral medications.

Exploring the Gut-Brain Relationship in PD

Research suggests that what happens in the gut influences the brain by way of the gut-brain axis — a biochemical communication between the gastrointestinal tract and the central nervous system.

While research on Parkinson's and the microbiome is in its infancy, scientists have found the gut bacteria in people living with PD differs from that of people without PD.

In Parkinson's, alpha-synuclein proteins misfold and form clumps in the brain. These clusters are called Lewy bodies. It has been suggested that these clumps, which are also found in other neurodegenerative diseases, may trigger the loss of dopaminergic neurons. As scientists have dug deeper into Parkinson’s progression, they have also been able to find alpha-synuclein pathology along the GI tract in people with Parkinson's.

What Science Can Tell Us

Gastrointestinal dysfunctions are some of the most common and troublesome non-movement symptoms in PD. Constipation affects up to 70% of people with Parkinson's and often begins before the onset of PD’s telltale movement symptoms and other early signs.  It's estimated that up to 75% of people with Parkinson's will also experience speech and swallowing issues. Gastroparesis, delayed emptying of the stomach, is another common PD symptom.

Knowing that alpha-synuclein pathology can also be found along the GI tract in Parkinson’s, over the years researchers have genetically sequenced the microbiome of different people with Parkinson's. They found that some beneficial bacteria, such as Prevotella, Faecalibacterium and Roseburia, are reduced in people with Parkinson's, when compared to someone without the disease. However, researchers also found a boost in other bacteria, such as Bifidobacterium and Lactobacillus, in people with PD — possibly due to constipation.

Research also shows zonulin, a protein marker of intestinal absorbency, found in inflammatory GI conditions such as celiac disease, inflammatory bowel disorders (IBD), diabetes and other autoimmune diseases, is also significantly elevated in people with Parkinson’s. This increased intestinal permeability potentially leads to what is referred to as “leaky gut” (a decrease in the intestinal barrier that can set off inflammation and disease).

Diversity Matters

A healthy microbiome is a diverse one. Research shows decreased microbial diversity in people with inflammatory bowel disorders, such as ulcerative colitis and Crohn's disease, compared to the resident gut bacteria in healthy people.

Diseases, including Parkinson's and IBD, diet and lifestyle all impact gut bacteria diversity. What we eat, how often we exercise, where we live and stage of life all play a role. Other influences include stress, antibiotic and pharmaceutical drug use and pollutants.

Researchers theorize that these factors influence the production of signaling metabolites, which determine whether the gut makes beneficial, anti-inflammatory or inflammatory molecules, such as those that impact cholesterol metabolism, cardiovascular and brain health and more. Communication among signaling metabolites can influence the GI tract, immune system, the liver, brain, lungs, skeletal muscle and other areas of the body.

While various factors can impact on gut microbiota, generally, the microbiome is very stable. Antibiotic or probiotic use often shows short-term changes in resident microbiota, but over time — as a person discontinues use of such medication or supplements and reverts into a familiar diet — the resident microbial makeup typically returns to where it was.

Taking Charge Through Diet

One of the best strategies to improve gut health is increasing fiber. While a probiotic may only introduce one bacteria strain, a fiber-fueled diet can be broken down by multiple types of gut bacteria to encourage a new microbial community to take up residence in the gut, benefitting GI and heart health, improving immune function and easing constipation.

When gut bacteria break down fiber it naturally produces health-boosting short chain fatty acids. These acids boost the gut’s mucus barrier to fight inflammation, protect brain and heart function and more.

Research shows a high-fiber, whole food, plant-fueled diet, with high consumption of fruits and vegetables (known as a Mediterranean-style diet) can increase butyrate and other beneficial bacteria. Right now, researchers are interested in butyrate, a fatty acid that is a major energy source for creating healthy new gut bacteria and can influence immune function.

Plant-Rich, Fiber-Driven Meals Matter

A Mediterranean-style diet is associated with lower risks of developing Parkinson’s, higher microbial diversity and improved heart and cognitive health. Studies also show incorporating this whole-food based diet, along with healthy fats, such as extra virgin olive, oil, nuts and seeds can ease PD symptoms.

To boost gut health experts recommend:

• Eating at least 14 grams of fiber for every 1,000 calories — about 28 grams for someone eating 2,000 calories a day. The average American only consumes half of the recommended daily fiber.
• Filling half your plate with vegetables and fruit.
• Eating prebiotic fibers such as bananas, onions, garlic, chicory root, artichokes, beans, grapes and cranberries.

For some people with Parkinson’s, taking certain PD medications with a protein-rich meal — like meat, fish, eggs, dairy products, nuts and beans — may interfere with absorption, slowing medication effectiveness. Talk to your doctor about whether a protein-redistribution diet, a popular solution for motor fluctuations, might be right for you. This means eating most of your daily protein during your last meal of the day.

On the Horizon

The research on dietary interventions to alter gut microbiota is entering a new era. Scientists are currently exploring:

• Probiotics: benefits specific to probiotic species and strain. Healthcare experts use the Clinical Guide to Probiotic Products Available in USA to inform research-based recommendations. There is no recommended consumption of probiotics in PD but bring up this topic with your doctor.
• Postbiotics: “a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host,” according to the International Scientific Association for Probiotics and Prebiotics (ISAPP). Studies show potential for using postbiotics to ease symptoms of irritable bowel syndrome, treat infections and more.
• Synbiotics: prebiotics combined with probiotics, defined by ISAPP as “a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host.” These are being investigated to potentially improve PD symptoms and more.

Researchers are also investigating how machine learning and artificial intelligence might aid in modifying gut bacteria. Entering information from an individual’s stool sample, diet, genetics and other medical data into a machine-learning model could identify precision nutrition to modify a person’s microbiome.

Learn More

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

• Podcast: The Role of the Microbiome in PD
• Blog: How an Innovative Research Center Studies the Gut–Brain Connection
• Science News: Stool Samples Could Detect Early Parkinson’s
• Library: Nutrition and PD

Researchers found changes in molecules in the brain and blood that are associated with Parkinson’s, they also found changes linked to certain symptoms

Two of the most widely recognized hallmarks of Parkinson’s disease (PD) are tremors and slowed movement. However, when these symptoms appear, it means that people with PD have already lost up to 60% of their dopamine neurons. Neurons are nerve cells in the brain that are crucial for maintaining a balanced and functioning nervous system.

Diagnosing and treating Parkinson’s early can fend off severe symptoms for years. Inversely, when a diagnosis is delayed, rapid decline can be more likely to occur. Unfortunately, there are no tools, besides assessing symptoms, to diagnose Parkinson’s or predict the course of the disease. However, a new study in Nature Communications has found evidence of molecular changes in the brain and blood of people with Parkinson’s who experience cognitive and movement complications of PD.

Finding molecular changes in the blood that mirror changes in the brain is essential for developing new minimally invasive tests that can diagnose Parkinson’s, be able to track the course of the disease, and monitor how it is responding to treatment.

Parkinson’s symptoms are primarily caused by the death of dopamine neurons in the brain. Dopamine allows us to regulate motivation, memory, cognitive functions, and motor skills. One critical region in the brain that relies on dopamine for these functions is the striatum, which has two regions that behave differently in Parkinson's:

• The caudate: When dopamine levels drop in this area, it leads to cognitive impairment.
• The putamen: When dopamine levels drop in this area, motor control is impacted.

Both regions are densely populated with the same kinds of neurons. While we know how these areas impact movement and cognition, we still do not understand the molecular mechanisms underlying these distinct responses in the human brain.

To learn more about changes in these brain regions, which are difficult to study as they are deep in the brain, researchers used brain samples from 35 people who died with Parkinson’s and 40 people who died without neurological issues. They looked for changes in RNA (a molecule essential for various biological processes) and identified thousands of RNAs that were different in those with Parkinson’s compared to those who did not have the disease.

Study Findings

1. RNA changes in the brain: Many of these RNA changes were linked to the function of the synapse, the special connection between nerve cells that allow them to communicate with each other. Researchers found decreases in RNAs involved in dopamine neuron dysfunction and death; an increase in RNAs involved in inflammation and immune hyperactivation; and an increase in RNAs involved in stress response.

2. Mirroring patterns in the blood: To compare whether the changes they observed in the brain were mirrored in blood samples, the researchers accessed samples from the Parkinson’s Progression Markers Initiative (PPMI), which has collected blood from people who do and do not have Parkinson’s. They found that the RNA levels in the brain were altered in the same direction in the blood.

3. Changes associated with cognitive impairment: The researchers found 57 RNAs in the caudate that were significantly altered in donors that had been diagnosed with Parkinson’s disease dementia. When researchers looked at the differences in RNAs in the blood of people with PD vs. healthy controls, they found a few RNAs that were altered in people with PD.
4. Changes associated with movement symptoms: The researchers found 18 RNAs in the putamen that were significantly altered in donors who experienced levodopa-induced dyskinesia. When researchers looked at differences in RNAs in the blood of people with PD vs. healthy controls, they found no significant differences.
5. Differential patterns depending on age at PD onset: The researchers also found differences between the brains of people who were diagnosed with Parkinson’s before and after the age of 55 — those who were diagnosed earlier showed fewer molecular changes than those who were diagnosed later. Similar results were found in blood.

Study Highlights

• People with Parkinson’s have unique changes in RNA molecules in brain regions that rely on dopamine for regulating motivation, memory, cognitive functions, and motor skills.
• Similar RNA changes were also observed in blood samples of people living with Parkinson’s.
• Patterns of RNA changes were associated with certain symptoms (e.g., cognitive decline, motor complications) or disease features (e.g., early vs. late onset).

What does this mean?

Today, only invasive tests can track molecular changes in the brains of people with Parkinson’s. This study has found that molecular changes that happen in the brain can also be found in the blood. In the near future, this information can be leveraged to develop minimally invasive blood tests that could be used to help confirm a Parkinson’s diagnosis, track disease progression, and evaluate how the disease is responding to treatment. However, more studies are needed before these findings can be used as a clinical tool.

What do these findings mean to the people with PD right now?

People with Parkinson’s symptoms should talk to their doctor about screening.

Learn More

The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about PD and the topics in this article through our below resources, or by calling our free Helpline at 1-800-4PD-INFO (1-800-473-4636) for answers to your Parkinson’s questions.

• Getting Diagnosed
• Can We Put the Brakes on Parkinson’s Progression?
• A New Test Could Detect Parkinson’s Before Symptoms Appear
• Join A Study

Launching a new Parkinson’s disease (PD) drug can take years and cost upwards of one billion dollars. In our latest Neuro Talk, John L. Lehr, president and CEO of the Parkinson's Foundation, and Arthur Roach, director of the Parkinson’s Virtual Biotech at Parkinson’s UK, discuss how the Parkinson’s Virtual Biotech is accelerating PD drug discovery and development. John and Arthur share how this international collaboration will help find the next life-saving Parkinson’s drug in years, not decades.

Learn more about the Parkinson’s Virtual Biotech.

The blood-brain barrier, a network of blood vessels that act as a security system to protect cells in the brain, is an understudied but vital area in Parkinson’s disease (PD) research. This barrier allows essential nutrients to enter the brain and keeps unwanted substances out, but the barrier deteriorates in people with PD. Aurélie de Rus Jacquet, PhD, is working to understand how inflammation can affect the permeability of the blood-brain barrier and identify potential therapies to address the problem.

“The blood-brain barrier is sort of the filter that allows good molecules to enter the brain, but prevents others from entering, therefore keeping them in the blood,” said Dr. de Rus Jacquet. “If that barrier stops working properly, a number of molecules that should stay in the blood may actually enter the brain and could end up triggering inflammation, neurodegeneration and all kinds of features that are really detrimental to the brain and are features of Parkinson’s disease.”                

Using a 3-D cellular model of the blood-brain barrier, Dr. de Rus Jacquet studied brain cells called astrocytes, which typically regulate the blood-brain barrier, from both people with and without the PD-related LRRK2 G2019S mutation. She found that the Parkinson’s astrocytes secrete harmful molecules and impair the filter function of the blood-brain barrier.

Now, she will study how astrocytes communicate with the immune system and look to identify the molecules that sneak through the blood-brain barrier and trigger neurodegeneration.

While a lot of existing and developing pharmacological therapies are focused around dopamine replacement, Dr. de Rus Jacquet’s research is looking to tackle Parkinson’s from a different angle.

“A lot of effort over the past decades has been focused on trying to find a therapy for dopaminergic neurons,” she said. “But maybe the question is, do we need to find a therapy that addresses dopaminergic neurons and other brain cells as well? One of the goals of this research is to find a way to target the potentially toxic molecules entering the brain from the blood early in Parkinson’s disease, before the neurons die. If we can identify and target those molecules before they enter the brain, it will facilitate drug discovery and success for future therapies.”

Dr. de Rus Jacquet started this important research during her Parkinson’s Foundation Postdoctoral Fellowship at Université Laval, Québec, Canada. Afterward, she went on to receive a Parkinson’s Foundation Launch Award to continue this research and has successfully transitioned to her own independent faculty position at Université Laval, where she now operates her own research lab. She recently published a paper on her research in Nature Communications.

“The support of the Parkinson’s Foundation has made a profound impact on my research and my career,” Dr. de Rus Jacquet said. “This work is very complicated and expensive, and the Foundation’s continued support allowed me to smoothly transition everything from my postdoctoral research into my own lab without any gap in timing.”

Dr. de Rus Jacquet is excited to continue to learn more about the blood-brain barrier and how better understanding of how it functions in people with PD can lead to new treatment options.

“Innovative research is what is necessary to make a difference in PD,” said James Beck, PhD, Parkinson’s Foundation chief scientific officer. “But innovation is not something you buy in a store — it takes people. This is why the Parkinson’s Foundation invests in scientists like Dr. de Rus Jacquet who have the insight, creativity and dedication to find new strategies to halt or prevent neurodegeneration in people with PD.” 

Now that she is running her own research lab, Dr. de Rus Jacquet is excited to work with students who are interested in PD research and is working to promote diversity in the patient population involved in research studies.

“I have moved on to a new stage where I can continue doing this promising research but also be impactful in other ways,” she said. “I can train the next generation of scientists and get them excited about this work. I can serve on committees working to reach out to a more diverse Parkinson’s population, which is so important to better understanding this disease. None of this work would be possible without the support I’ve received from the Parkinson’s Foundation and the donors who believe in this cause and this research. I’m deeply touched, and I am so grateful.”

For more information on our research grants, visit Parkinson.org/Grants.