Dan Keller 0:02
Dan, 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. Most people with Parkinson's disease will experience gastrointestinal problems at some point in their journey, making the gut microbiome a big focus of Parkinson's research over the past decade. Today I'm speaking with movement disorders neurologist Dr. Lisa Deuel of the University of Vermont Medical Center. She explains how the gut and brain are connected and discusses common gastrointestinal problems in Parkinson's, such as constipation and slowed stomach emptying, called gastroparesis. She also shares practical strategies to support gut health. So I first asked her to put in perspective the gut microbiome as it relates to Parkinson's. 

Lisa Deuel 1:20
The microbiome is a term we're hearing a lot more, and what that refers to specifically, with regards to the gut, is the microbes—so, any bacteria and viruses that essentially live, in this case, in the gastrointestinal tract. You can have a microbiome other places in your body as well, but when we think about the microbiome as it pertains to Parkinson's, we're often talking specifically about the gastrointestinal tract. And I think of it, you know, we're almost trained to think of bacteria and viruses as being bad and being associated with illness and infection, but this microbiome is actually part of what we call a healthy gut, and needs to be there in order for the gut to work properly. It's there from birth, and there's a lot of different things that can shape the microbiome. So, just even the way that you're delivered at birth can impact what your microbiome ends up looking like; your genetics can play a role in what your microbiome looks like, and as we'll talk about, we know that the microbiome tends to look different in people with certain diseases, including Parkinson's disease.

But the microbiome is really important because it helps our bodies to develop a healthy, working immune system. It helps with the way we digest food and absorb nutrients and vitamins from our food. It actually—some of the bacteria produce chemicals that actually help to communicate from the gut to the rest of the body, including the brain. So, it gives signals communicating what's going on in your gastrointestinal tract, and then, you know, how that impacts the rest of your body. So, it actually not only impacts just the gastrointestinal tract, as we would assume, but it really has connections with the entirety of the rest of the body.

Dan Keller 3:16
And a normal microbiome seems to keep things pretty well in check and functioning properly. People without it get into trouble.

Lisa Deuel 3:26
Exactly. We have data to suggest, again, not just in Parkinson's, but in other diseases as well, that there may be changes to the microbiome. Where it gets really tricky is trying to figure out, you know, are those changes happening at the beginning, and therefore causing the disease, or are these changes that we see as a result of the disease? And we don't necessarily know how these changes impact the start of a disease like Parkinson's disease, mostly because we have a lot of data to suggest that the changes going on from a molecular level in Parkinson's disease are happening long before a person actually develops the classic symptoms that we think of, like tremor and walking trouble and slowness of movement. So, it's hard to know exactly how these changes to the microbiome actually cause or affect the disease process.

We just know when we take a group of people with Parkinson's, for example, and we look at the pattern of the bacteria that we see in their gastrointestinal tract, that it looks different than people who don't have Parkinson's disease. Again, it's not just one specific bacteria that is or isn't there; it's more so the pattern, and that the pattern in Parkinson's disease tends to be more inflammatory. So, these types of bacteria are more likely to cause inflammation or irritation of the gastrointestinal tract, and so when we start to notice these patterns, and we see more susceptibility to inflammation, there are theories that this then makes the gut leakier. Perhaps that's an entryway for toxins, potentially toxins from the environment, or things that we ingest to enter the body.

Dan Keller 5:28
There seems to be at least two hypotheses: gut-first or brain-first. The things you see in the gut are a result of what was going on in the brain, or things that precede symptoms may start in the gut and move up to the brain. Where does that stand?

Lisa Deuel 5:48
I think that's exactly right, that there's these two ideas going on, and there's data out there that supports either of them. And it may be the case that we're lumping a lot of people into one category called Parkinson's disease, but maybe there are actually different processes, different disorders that end up with the same symptoms, and we're limited by our ability to diagnose people based on what we see clinically. We can't really categorize people by what's going on inside the body, and so I think that's where it stands, is there's limitations based on how we're able to obtain data and characterize people.

But there is a lot of interest in looking at the microbiome, looking at people who, let's say, have a family history of Parkinson's, so may be more likely to develop symptoms in the future, and really try to categorize these things as early as possible, so you might be able to tease out the difference: is it coming more from the gut or is it coming from the brain, or are there two separate, let's say, populations of people? So, maybe both theories are correct, and again, that's where there's a lot of interesting research going on to try to help answer these questions, and really find out, could any of this, whether it's the microbiome or other chemical changes in the body, could those be considered a biomarker that if we look at that early in people who don't have Parkinson's disease, it might predict whether or not they're going to develop symptoms?

Dan Keller 7:31
Can changes in the gut affect the symptoms or progression of the disease?

Lisa Deuel 7:37
Yeah, it seems like modifying the microbiome can affect Parkinson's symptoms. I think whether or not that's changing the disease process itself or changing how your body can, let's say, absorb and utilize medications is kind of a question up in the air. What I mean by that is the way that people have looked at this so far is to, let's say, in some current research, give people a probiotic. And the idea with a probiotic is that we're helping to build up more of the good, healthy, less inflammatory microbiome, and then these small studies, so far, have shown that that can be really effective in improving Parkinson's symptoms.

But I think a question that still remains is, are we actually changing what's going on with the Parkinson's as a whole, or are we changing the way that the gastrointestinal tract is able to kind of break down and absorb medications and thereby just making the medications more accessible, so somebody feels better? I will say, too, there's plenty of data out there suggesting that something like a probiotic can help with the gastrointestinal symptoms—so not the motor symptoms necessarily, but people dealing with constipation, which is a very common issue in Parkinson's, that that can actually respond to a probiotic as well. So, there's a lot of different ways that somebody with Parkinson's could benefit from, let's say, a probiotic to change the microbiome.

Dan Keller 9:14
I always think that if our microbiome changes, whether we've had a powerful antibiotic or some other condition causes it, maybe we should have banked stool samples when you were healthy, sort of like doing cord blood transplants.

Lisa Deuel 9:32
Sure, there's interesting research, and maybe a little challenging to talk about, but there's some interesting research starting with animal models, with mice models, where they can effectively transplant the microbiome from, let's say, a healthy mouse into a Parkinson's mouse model, and you can see a reduction in Parkinson's symptoms. And they do the opposite as well, where they take a mouse with a normal, healthy gut microbiome, and then they implant the microbiome from a Parkinson's mouse, and again, you can induce more Parkinson's symptoms in mice models. So the idea there, in practice, it's challenging, but this is actually a process that's done that's called fecal transplant. It is done more for people with severe diarrheal illnesses, where you're trying to clear out that bad gut microbiome for somebody that's having really severe gastrointestinal symptoms, but it is effective as a treatment.

There have been small studies that have shown if you do a microbiome transplant through a fecal transplant in humans, you could also improve symptoms as well. If you really get into the weeds of this, it's perhaps a little bit not palatable in a certain way, but they can transplant the healthy microbiome. So, some people would find that type of treatment to be a little bit questionable, but there have been small studies that suggest it works. The trick again with Parkinson's is, you know, this is not something that we're doing ahead of time, and most people who develop Parkinson's don't realize early on that that's something they're going to develop in the future. So, unless we could come up with some sort of marker that would indicate somebody's risk for developing Parkinson's, you would just have no idea that you needed to do this in the future.

Dan Keller 11:30
Gastrointestinal issues can be pretty common in people with Parkinson's: constipation, gastroparesis, which is slowed emptying of the stomach, and they can be frustrating to people, and also embarrassing to talk about, even with their physician. So, how common are these kinds of symptoms in people with Parkinson's?

Lisa Deuel 11:51
You're right, they're very common. Some studies show up to 80% of people with Parkinson's have constipation; that's what we tend to talk about the most. But you're right, there are other symptoms related to the gastrointestinal tract that can be present as well. It is really hard, right? These are things that we're not used to talking about frequently. I'll say in my office, that's something I talk about a lot. So, I've gotten a little bit more comfortable over time, and a lot of these, you know, what we refer to as non-motor symptoms—it's important for us, as the clinicians, to ask about them, because people don't necessarily realize that it comes along with Parkinson's. Again, we often think about the motor symptoms, and people aren't aware of just how common some of these non-motor symptoms, like constipation, can be.

So, my approach is just be open about it and ask questions to try to get to the bottom of what's going on. You know, at times it makes people feel a little uncomfortable, but ultimately, you know, we're all just trying to work together to help somebody feel better. And oftentimes, I'll say constipation is a great example of that, that sometimes these non-motor symptoms can be worse than some of the motor symptoms that we're used to dealing with. So, I've learned over the years that if I don't ask, if we don't have some way of capturing the information, either through our intake forms or by asking directly, that this is a symptom that somebody might not offer up because of embarrassment or just not realizing that it's related. But it's really important because it's not something that you're necessarily seeing a gastroenterologist for. Most people don't see a gastroenterologist routinely for mild constipation, so I find in my clinic it's one of the common things that we're managing and treating.

Dan Keller 13:50
Constipation would be considered a non-motor symptom, but in essence, doesn't it have to do with the motility of the gut, the muscles, the smooth muscle of the gut propelling things through it?

Lisa Deuel 14:03
Sure, that's a good point. The term motor symptom we generally refer to as more of the mobility, the tremor, things that to some degree are visible as affecting the muscles, but it's a good point. You have a whole separate nervous system within the gut. The reason I think it's worth differentiating, though, is often the treatments are very different. So, when we give medications to treat the common motor symptoms of Parkinson's, we're thinking about stiffness and slowness and tremor. We have a number of different medications we can use to help with those symptoms. Those medications that help with the typical Parkinson's symptoms often don't help these other non-motor symptoms, and in fact, sometimes the medicines we use to treat Parkinson's can actually make non-motor symptoms worse, like constipation. So, there's a number of Parkinson's medicines that we would give to, say, help with a tremor, and we actually have to counsel people to watch out for worsening of their gastrointestinal issues.

Dan Keller 15:12
What are some practical steps that people can take to improve their gut health?

Lisa Deuel 15:19
We have a lot of different things we recommend, and generally starting from more conservative to more advanced, depending on the situation. In general, though, I would tell everybody, I guess, with Parkinson's or without Parkinson's, is to stay hydrated, drink plenty of water. I tell my patients, obviously, depending on the situation, even up to one or two liters of water a day, and that can really help with a lot of things, but constipation, too. And then eating a diet that's high in fiber, so trying to get in as much fiber as you can, can help with some of these symptoms that we're talking about.

We talked about probiotics a little bit, and how that can be a positive impact on the microbiome, and introduce more of those good, less inflammatory bacteria. So that's an option, especially as I said, there are small studies that say it can be helpful for constipation as well, and the other things we always think about is just eating healthy in general. Being more active can also be helpful here, and vice versa. The better your gut health, the better you're feeling. The better you're absorbing your medications, the more easy it is to be active as well.

Dan Keller 16:41
Since we're talking about the gut microbiome, it seems there's a lot of commercial companies now offering home gut microbiome tests, but there seems to be no standardization, no regulation, not even proficiency testing for the different companies offering different collection methods, different processing methods. Some are looking for DNA to know what's in the gut, some are looking for RNA or even metabolites of gut microbes. Then you've got the issue of sending in the sample through the mail: time, temperature, or bacteria dying off or proliferating. So, is there any utility to these kinds of tests, are they worth doing, and then if so, what do you do with the results once you have them?

Lisa Deuel 17:25
That's exactly the big question, is what do you do with the results, and I think to take a step back, it just reiterates what we've been talking about, which is, you know, we know the microbiome and Parkinson's, and again in other neurologic and non-neurologic disorders too. We know the microbiome is different, but we don't know exactly how it's different or how it gets that way, and so I worry about right now being in the midst of this research and not having really good conclusions about what the data means, is that you spend a lot of money on some of these tests. And it is really interesting, the different things that they can test nowadays, but it's hard to really know what to do with that data, so I generally tell people right now to not spend the money and maybe invest more, like we talked about, in just overall better diet and gut health by way of diet and exercise and hydration, rather than spending a lot of money for something we don't know how to interpret.

Dan Keller 18:28
As research in this area marches on, what gives you the most hope about the future of gut health knowledge about it as it relates to Parkinson's?

Lisa Deuel 18:39
I think the reason that it interests me so much is because we're still trying to answer this question, of course, of what causes Parkinson's disease. Is it truly one disease, or is it multiple different causes of different diseases that ultimately look the same downstream? And we've heard before about this idea that genetics plays a role, but the environment plays a role. This is a way to kind of tie those things together in a sense, and I think that's why I find it fascinating is thinking about how the environment might impact your gut microbiome, and then have a downstream effect.

And then if we can come up with a pattern to use the microbiome as a biomarker for people being at risk for the disease, that's something you can look for; you can look for that pattern in people without Parkinson's to really quantify their risk of developing it. So, I think it's interesting to me to fold in that there's some evidence if you adjust the microbiome, whether it's through diet or these different experimental capacities that I talked about, you could make somebody feel better in the moment, but also if you look more into the microbiome, you might be able to predict who's going to develop Parkinson's down the line, so that you can intervene a lot earlier.

Dan Keller 20:07
Very good, I appreciate it. If you'd like to know more about the gut microbiome in relation to Parkinson's disease, you can search for "microbiome" on our website at parkinson.org. You'll find several blog posts, news articles, and a past podcast. 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'd like to leave feedback on this episode or to let us know what other topics you'd like us to cover, visit Parkinson.org/Feedback. Be sure to subscribe and rate us 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 month. Till 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. 

Lisa Deuel, MD is a Neurologist and Movement Disorder specialist at the University of Vermont Health Network in Burlington, VT. She completed her Neurology residency at Albany Medical Center in Albany, NY followed by a two-year Movement Disorder fellowship at the University of Colorado in Aurora, CO. 

In her current role, she provides comprehensive, patient-centered care for individuals with PD and other movement disorders. She has particular interest in gastrointestinal symptoms associated with PD, especially the relationship between gut health, environmental exposures, and inflammation on symptoms and disease progression.