Dan Keller 0:08
Welcome to this episode of Substantial Matters: Life and Science of Parkinson's. I'm your host, Dan Keller. At the Parkinson's Foundation, we want all people with Parkinson's and their families to get the care and support they need. Better care starts with better research and leads to better lives. In this podcast series, we highlight the fruits of that research—the treatments and techniques that can help you live a better life now, as well as research that can bring a better tomorrow. While our bodies consist of our own human cells, they also contain and interact with a vast array of microorganisms. These microbes normally keep us healthy, maintaining a balance on our skin and within the various niches within us. A major repository of microbes is the human gut, from the stomach through the large intestine, which contains about 1,000 kinds of bacteria, along with fungi and other organisms. These microbes are essential for digestion, the production of vitamins, and immune regulation. Mounting evidence indicates that, in addition, they influence the nervous system, including the brain. They can also affect drug absorption, metabolism, and elimination from the body. For this second podcast on the microbiome and Parkinson's, I speak with Ai Huey Tan of the University of Malaya. She studies the relationship of the gut microbiome to Parkinson's and tells me about her work and that of other researchers. Before she describes how the microbiome affects the disease, she starts off by describing how the disease affects the gut.
Ai Huey Tan 1:56
As we all know, Parkinson's is more than just a movement problem. Patients with Parkinson's suffer from non-movement, or what we call non-motor problems, as well, and in this regard, problems related to the gut can be very common in patients with Parkinson's. And this can include drooling of saliva, difficulty in swallowing, bloatedness, constipation. Several studies have even shown that up to maybe about 70% of patients with Parkinson's can experience constipation in their disease course, and this can be due to reduced gut motility or dysfunction of the anal sphincter itself.
Dan Keller 2:37
We know there's feedback from the gut to the brain. We feel full when we eat. Sometimes we feel nauseous. So what kind of transmission is there, or cross-talk between the two?
Ai Huey Tan 2:49
Yes, you are right. The brain and the gut communicate through several pathways. One will be the neuronal pathway where the vagus nerve and the enteric nervous system are thought to play a major role; two, via hormonal or metabolic signaling; and three, via an immune pathway.
Dan Keller 3:09
There's been increasing interest about the gut microbiome. What do we mean by microbiome?
Ai Huey Tan 3:15
Microbiome refers to the microorganisms that live in a particular environment. Our body harbors a huge array of microorganisms, and we actually have 10 times more microbial cells in our bodies as compared to human cells, and the majority of these microorganisms live in our gut, especially in the large bowel. We also know that microbiomes from different parts of the body differ from one another, i.e., the microbiome composition in the oral cavity is very different from the microbiome composition in the large bowel itself.
Dan Keller 3:55
Does the microbiome change over the course of the disease, and which causes which? Is the microbiome affecting the disease? Or is the disease affecting what's in our gut?
Ai Huey Tan 4:05
We know that the gut microbiome evolves from infancy all the way through puberty, as we experience changes in our diet and also expansion in our gut mucosa, and the microbiome composition becomes fairly stable once we reach adulthood and remains stable for quite a number of decades, but it may experience changes again as we enter the aging process. Now, many studies on gut microbiome in Parkinson's disease are cross-sectional in nature. That means they only look at one time point. There is only one study that looked at several bacterial groups over a period of two years in Parkinson's disease. So we do not really have enough data to tell us whether the gut microbiome actually evolves through the disease course in Parkinson's disease. We also do not have enough data to say whether or not it is Parkinson's disease that affects the gut microbiome or vice versa. But my gut feeling about this is that it's probably bidirectional. They contribute to each other in a bidirectional way.
Dan Keller 5:15
The large intestine, the colon, has a much greater load or burden of microbes than the small intestine, but there is something called SIBO—Small Intestinal Bacterial Overgrowth. Is there significance to that?
Ai Huey Tan 5:30
Small intestinal bacterial overgrowth is an acquired condition where there is an increased amount of bacteria, or changes in the type of bacteria, in our small bowel. There are quite a number of risk factors for SIBO, which can include low stomach acid, reduced gut motility, recurrent use of antibiotics, and proton pump inhibitors. So patients with SIBO can experience bloating, belching, diarrhea, and constipation. In Parkinson's disease, SIBO has been associated with worse disease severity and longer "off" time and more episodes of delayed "on" time or dose failure, where there is no "on" time at all when the patients take their Parkinson's medication.
Dan Keller 6:18
Do you know if it's because of absorption, or is the small intestinal microbiome breaking down the drug?
Ai Huey Tan 6:25
We now have some evidence that SIBO may affect Parkinson's medication absorption in the small bowel.
Dan Keller 6:33
Let's move up the gastrointestinal tract to the stomach. We've heard a lot about Helicobacter pylori, H. pylori, and its causing stomach ulcers. But what is the significance of H. pylori and Parkinson's?
Ai Huey Tan 6:49
Well, there are quite a number of studies regarding H. pylori infection in people who have had Parkinson's disease. So the prevalence of H. pylori infection in Parkinson's ranges from about 32% to about 70% in all these various studies. H. pylori infection in Parkinson's has been associated with worse disease severity and, again, with worse motor response complications such as longer time for medications to take effect and also shorter "on" periods.
Dan Keller 7:24
Many people have H. pylori and they don't get stomach ulcers. Is there a reason to think of eliminating H. pylori in people with Parkinson's disease, even if they don't have stomach ulcers, because of its effect on the medication? Or is it really too early to say we should do something about it?
Ai Huey Tan 7:44
At the moment, we have a few studies looking at the effect of H. pylori eradication in Parkinson's disease. There is one well-conducted randomized controlled trial that looked at the effect of H. pylori eradication on motor response complications in Parkinson's disease. They were able to show that after eradication of H. pylori, patients improved in terms of their "on" time after taking the Parkinson's medication. And in their basic pharmacokinetic studies, they found that the bioavailability of levodopa actually improved by about 20% after H. pylori eradication. So there is some evidence that by eradicating H. pylori infection, especially in patients who have motor response complications, this may improve medication absorption and therefore improve the duration of action for these medications. But at the moment, there is a lack of well-conducted, randomized controlled trials in this field to make a standardized recommendation across the board. So hopefully we will see more high-quality trials in this field in the future.
Dan Keller 9:01
Are there any recommendations about diet in Parkinson's? Are there any types of foods that people should think of eating or think of avoiding?
Ai Huey Tan 9:10
Generally, a normal, healthy, balanced diet is recommended without any special restrictions.
Dan Keller 9:18
What about probiotics? A lot of people have been talking about them for a lot of things. Do any of these supplements have a proven effect in Parkinson's disease? Is it too early to make a recommendation? Can they even be harmful?
Ai Huey Tan 9:30
We have a recent well-conducted randomized controlled study looking at the use of probiotics in treating constipation in Parkinson's disease, and the researchers were able to show that probiotics, in combination with prebiotic fiber, were effective in improving constipation and without any significant adverse events. So probiotics can be considered for patients with Parkinson's disease who are experiencing constipation. There is still a lack of studies on probiotics in Parkinson's disease. It is hoped that in the future, with further advancement in scientific knowledge, doctors will be able to prescribe certain specific dietary interventions or specific supplements based on the understanding of the diet and also the microbiome in Parkinson's disease.
Dan Keller 10:24
It sounds like this is a whole wide-open area for research. People have looked at the drugs, people have looked at motor symptoms, non-motor symptoms, but the microbiome and the gut seems to be just a new field entirely.
Ai Huey Tan 10:37
Yes, and this is a very exciting field, and we can see there are more and more studies being produced in this field over the past three to four years. And hopefully in the future, we will be able to understand better the bidirectional connection between the brain and the gut and the gut microbiome. And hopefully we can use some of this knowledge to potentially help identify, perhaps a biomarker for Parkinson's disease, and also probably to consider whether we can modulate the gut microbiome effectively in Parkinson's disease to change the disease course or to treat certain aspects of the disease. And we hope that this research will ultimately benefit our patients with Parkinson's in the future.
Dan Keller 11:29
Excellent. Thank you. To find out more about the microbiome, the gut-brain connection, and how gut bacteria may be linked to Parkinson's symptoms, search our PD library for fact sheets, articles, and more at parkinson.org/library. There's also an expert briefing on nutrition and PD at parkinson.org/eb led by Dr. John Duda of the University of Pennsylvania, who discusses the possibility that sound nutritional choices may provide disease-modifying effects. And in Episode 68 of this substantial matter series, Dr. Ali Keshavarzian expands on the importance of our microbiomes in health and disease, with a particular focus on Parkinson's. Also for a general overview of research on the human microbiome, take a look at the National Institutes of Health's Integrative Human Microbiome Project at hmpdacc.org. As always, our PD information specialists can answer questions and provide information in English or Spanish about this topic or anything else having to do with Parkinson's. You can reach them at 1-800-4PD-INFO. If you have questions or want to leave feedback on this podcast or any other subject, you can do it at parkinson.org/feedback. If you enjoyed this podcast, be sure to subscribe and rate and review the series on Apple Podcasts or wherever you get your podcasts. At the Parkinson's Foundation, our mission is to help every person diagnosed with Parkinson's live the best possible life. Today, to that end, we'll be bringing you a new episode in this podcast series every other week. Until then, for more information and resources, visit parkinson.org or call our toll-free helpline at 1-800-4PD-INFO, that's 1-800-473-4636. Thank you for listening.
