Parkinson’s disease is a neurological disorder that attacks the nervous system. Researchers have long assumed that the disease starts in the brain, but a growing body of research indicates that, for some patients, it may actually start in the gut.
A new study led by researchers at Beth Israel Deaconess Medical Center found that individuals with a history of upper gastrointestinal damage, like ulcers, were at a 76% greater risk of developing Parkinson’s than those without such history.
Dr. Tricia Pasricha, senior author of the study, joined GBH’s All Things Considered host Arun Rath to explain the link between Parkinson’s disease and gut health. What follows is a lightly edited transcript.
Arun Rath: The list of symptoms we traditionally associate with Parkinson’s — you know, we think of things like a tremor or stiffness of movement — [don’t seem] to have anything to do with the GI tract. I’m wondering, when did researchers first get a sense that there might be a connection between the GI tract and Parkinson’s?
Dr. Tricia Pasricha: Yeah, that’s a great question. The idea that Parkinson’s might originate in the gut is a hypothesis that’s at least two decades old.
But, you know, the interesting thing is that when you talk to patients with Parkinson’s disease, a lot of them [are] affected by tremors and difficulty walking. But when you ask them [about their gut health], they say, “You know, come to think of it, I have experienced constipation that started years before the motor symptoms started.” Or they might say, “Yeah, I started to get this low-level nausea and I don’t know why, but that’s been going on for years.”
As more and more people started to experience this, researchers like myself and others in the field started to say, “Well, why?” Why do these people tend to have symptoms like constipation, irritable bowel syndrome, nausea and trouble swallowing — all of these GI symptoms — years, if not decades, before these other more commonly associated symptoms like tremors started?
Rath: Working from there — going back from two decades to where you are with your research — where did that lead?
Pasricha: Yeah. So, about a little more than two decades ago, this hypothesis came out, which is known as Braak’s hypothesis, based on the researcher who first really described it in the literature. The idea is that there’s some trigger that happens outside the brain and could be in the gut that causes this misfolding of the protein alpha-synuclein, which we know plays a role in the death of dopaminergic neurons in the brain.
Actually, we hypothesized that some trigger [causes] that protein to misfold, potentially in the gut first. As that protein misfolds, it propagates up from the gut through the vagus nerve and into the brain, where it ultimately does cause those classic symptoms, like tremors, difficulty walking and rigidity.
Rath: Does that lead to a way of maybe understanding the onset of Parkinson’s earlier than we might typically?
Pasricha: That’s the hope. I mean, you know, most of these symptoms — the GI symptoms — often start much earlier than the motor symptoms. The whole idea with the gastroenterologists in this field, as I am, is to try to identify exactly, if we can, what those triggers are that happen in the gut.
That’s what led to the current study and whether any of the pathology that happens in the gut before it reaches the brain can be intervened upon early. Our study was based on this hypothesis that was described in the literature [and was] only really mentioned once in a paper from the 1960s, in which a physician noted [their] patients with Parkinson’s tend to have more duodenal and gastric ulcers than other patients, and he didn’t quite understand why. And then the medical literature goes silent for a few decades on this question.
But then, when I became a neuro-gastroenterologist — and I’ve been practicing now for several years — I, too, started to notice among my own Parkinson’s patients that these people tend to report not just gastric ulcers but erosions and gut troubles years before they got their diagnosis.
That’s what led us to do this study in a large cohort of patients where we really examine what happens to people who have injury to the mucosa, or the lining of their guts. Are those people actually at an increased risk of getting Parkinson’s disease? And indeed, that is what we discovered.
Rath: Parkinson’s — just stating the obvious — it’s a terrible disease. It’s progressive. There’s no cure for it. Is it possible that if we could understand those kinds of triggers you’re talking about, it could be possible at some point to stop Parkinson’s before it starts?
Pasricha: Well, that is the hope, and certainly, that’s what we want to achieve one day with some of this research. You’re right that we don’t have any medications that, at this point, can halt the progression in the way that we’d like to see.
But if, at least in a subset of patients, we can confirm that the disease has started somewhere in the gut we do hope that we can identify what those pathways are and then target some sort of treatment. We’re not quite there yet.
A lot of people, after [reading about] the study, have been asking, “Well, what I can do to reduce my risk of Parkinson’s if I had peptic ulcers?” We don’t — we’re not quite at the point where we can say “This is exactly how you block that pathway from turning into full-blown Parkinson’s disease.” But what I can feel pretty comfortable telling people is that certain steps that will boost your gut health and help with your gut lining will only help you, regardless of your risk for Parkinson’s disease.
Reducing the number of NSAIDs [nonsteroidal anti-inflammatory drugs] like ibuprofen that you take, minimizing alcohol and, to the extent possible, reducing stress — these things all help your gastrointestinal mucosa and help your overall health as well.
Rath: There’s been a big spike in Parkinson’s disease. I didn’t realize this, but globally, apparently, it’s doubled in the last 25 years. Do we have a sense of what is the reason for that spike? And any sense of this new research giving us any clarity on it?
Pasricha: That’s a great question. The number of cases has really doubled in the last 25 years, to the point that some people are calling this a “Parkinson’s pandemic.”
Now, the biggest risk factor is age — we are a population that is aging — and there’s certainly a genetic component, but most people don’t have a known genetic risk. So we start to wonder what are the environmental factors that have been changing over the last several years and decades that could be leading to it? What of those environmental factors might be influencing our stomachs?
One of the environmental factors that we’re very interested in, of course, is food. The way we eat today is certainly not how people ate in the 1950s. It’s certainly not how people ate in the 1850s. We have a lot of different ways that we’re processing food. We’re ultra-processing foods. We’re eating higher-fat foods.
Those things do compromise the gut lining, even in low levels. We don’t yet know the exact role that those things are playing, but it’s certainly one of the factors that we’re looking into.
Rath: We’ve covered so much ground and big questions, but I want to throw in one more big one: Does this have any implications for research on the origins of other neurodegenerative diseases, like Alzheimer’s?
Pasricha: That is a great question, and it’s an important question. Alzheimer’s is also characterized by an abnormal protein in the brain. Alzheimer’s is also associated with a lot of significant GI dysfunction, including constipation.
I think, again, it’s a little bit too early for us to say that we’ve identified GI origins of any of these diseases precisely, but I think this type of study and others like it really do show that the gut and the brain are very closely connected. It’s not — as we often think about the gut-brain connection — just a one-way street in which our brain dictates what’s happening in our gut.
We often think, you know, when we’re nervous or we’re stressed, we get butterflies in our stomach or we suddenly have to go to the bathroom right before our turn at karaoke. That’s one pathway of the gut-brain communication, but we’re really starting to learn how much the influence the gut exerts on the brain in ways that we’re only beginning to understand.
