Parkinson's, Anxiety On The Forefront Of Gut-Brain Research : Short Wave TFW when you're so excited you get those butterflies in your stomach - or maybe when you see something icky, you feel ill. On today's show, producer Berly McCoy looks at this relationship between our gut and our brain. Berly talks to host Emily Kwong about how the organs evolved to have a tight connection - connections that go beyond transient feelings of excitement or disgust. In fact, an increasing body of research shows links between the gut and conditions we typically associate mostly with the brain – like anxiety and Parkinson's Disease.

Here's a link to the study about gut bacteria and the brain in some children with Autism Spectrum Disorder.

You Know That Gut Feeling You Have?...

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You're listening to SHORT WAVE from NPR.

Hey, SHORT WAVErs. It's Emily Kwong here, and I have a gut feeling you're really going to like this episode. Producer Berly McCoy is here. Hi.


KWONG: So I kind of hinted at it, but what do you have for us?

MCCOY: I've been thinking about all the ways our brain is connected to our gut.

KWONG: So you mean like when someone gets some really bad news and they feel it in their stomach? It's like a punch.

MCCOY: Yeah, or when you're so nervous, you feel like you could throw up or even seeing something really gross, how it might make you lose your appetite.

KWONG: Yeah, been there. We talk about gut reaction. We talk about follow your gut. It's just, like, in our language. But is there any basis in science?

MCCOY: There is. Our brain is super tied to our gut. For example, if we smell or think about food, our brain sends a signal to our gut to turn on gastrointestinal juices. How our brain controls our gut is super interesting, but there's more to this story. Scientists are learning that communication and control go both ways.

KWONG: So today on the show - how our brain talks and listens to our gut.

MCCOY: And how scientists are finding links between the gut and conditions we typically associate with the brain, like anxiety and Parkinson's disease.

KWONG: I'm Emily Kwong.

MCCOY: I'm Berly McCoy.

KWONG: You're listening to SHORT WAVE, the daily science podcast from NPR.


KWONG: All right, Berly. So today we're talking about the gut-brain connection. I guess my first question is, what do we know about why these two organs are so tightly connected? It seems, based on what you've told me, that they're yakking on the phone 24/7.

MCCOY: They really are. I talked to Dr. Jay Pasricha, a gastroenterologist at the Mayo Clinic. He says the two go way back evolutionarily.

JAY PASRICHA: The first brain - and by that, we mean a collection of nerve cells, an organized collection of nerve cells - formed around the gut in an attempt to better coordinate gut function and make it more efficient in terms of the ability to convert complex energy sources into forms that the body could use.

KWONG: Wow. That's super interesting.

MCCOY: Yeah. Jay says that organisms like bacteria or amoeba used simple small molecules as their energy source - their food, basically. But as those organisms started competing for small molecules and they ran out...

PASRICHA: Organisms had to evolve correspondingly complex guts to be able to break down those complex forms into simpler ones.

KWONG: That makes sense.

MCCOY: Yeah. Think amino acids, fatty acids, carbohydrates. So, like, even though I may eat a sweet potato for dinner tonight, my body breaks it down to use the components of that starch - so sugar - for energy.

KWONG: So you mean that the more complicated the food got - dare I say, the more delicious food became - the more sophisticated the gut had to get in response to be able to make digestion happen.

MCCOY: Yeah, exactly. And to make sure that orchestration of digestion happens smoothly, the nervous system needed to be even more involved.

PASRICHA: There is a clear progression in terms of the number and the structure of the nerves around the gut from almost nothing in very primitive organisms to as many neurons as in the spinal cord, or more, in human beings.

KWONG: Berly, Berly, Berly. Are you telling me that the gut and the brain co-evolved?

MCCOY: I am. And the gut became so sophisticated in animals that it developed its own nervous system...

KWONG: What?

MCCOY: ...Long before the nervous system that included our brains evolved. I talked to Sarkis Mazmanian. He's a scientist who studies the gut-brain connection at the California Institute of Technology.

SARKIS MAZMANIAN: So in addition to the neurons in our brain that we're quite familiar with, we have many neurons in our intestine. And so the neurons in our brain and spinal cord are called the central nervous system. The neurons, or the neural connections, in our intestines are called the enteric nervous system.

KWONG: So we have a whole other nervous system just in our gut.

MCCOY: Yeah, and it has hundreds of millions of neurons, some of which can act independently of our brain, although it still does get messages from the brain.

KWONG: It all makes sense. But to think about it in this way is pretty cool. So, Berly, let's talk about how these two nervous systems even talk to each other. We'll talk about the messages themselves later. But first, how are they communicating? So, like, Morse code? The tin cans?

MCCOY: Maybe. Sarkis says there's a few ways.

MAZMANIAN: So the enteric nervous system and the central nervous system communicate with each other via specific nerves, such as the vagus nerve, which, again, sends signals in both direction along the superhighway. Think of it as, like, a fiber-optics cable, if you will, that connects the two different tissues.

MCCOY: So these two nervous systems talk, not surprisingly, through nerves - some from our brain, down to our spinal cord and into our gut, and some through the vagal nerves. There are actually two of those that Sarkis just mentioned. They go from our brain through our neck and then down either side of our body and wind up in our gut. And one fact I found super interesting - most of the fibers in the vagus nerve send messages from the gut to the brain - like, 90%.

KWONG: Oh. So the gut does a lot of the talking, and the brain does a lot of the listening.

MCCOY: Yeah.

KWONG: And you said there are other ways they talk to each other. What are some of those?

MCCOY: Yes. So there's also immune connections between the two.

MAZMANIAN: Most of the immune cells in our body at any given point in time are sort of hanging out in our intestines. And they're being, for lack of a better term, educated by our microbiome. They're receiving signals from our microbiome, but also our diet and our environment. And that changes the function or the properties of those immune cells.

MCCOY: So those immune cells circulate in our blood and then they get near or into the brain.

MAZMANIAN: And then they essentially can transmit those signals into the brain. And this has been shown to change, you know, things like social behaviors in animals, but it also affects the immune response, how we fight off viruses or bacteria that may get into the brain as well.

MCCOY: So basically an infection in our gut can cause changes in the brain. And what those changes are, scientists are still learning. But then the third way the gut and brain talk is through molecules that are made in the gut. They go to the brain. Either they're made by our cells or by our gut microbes.

KWONG: OK. So sounds like three of the ways messages travel between the gut and the brain are through the vagus nerves, through our immune system and through molecules themselves. But, Berly, what are those messages?

MCCOY: This is the question. So this gut-brain field is pretty new. So scientists are just starting to tease this question out. I mean, there's literature going back centuries talking about how the gut and the brain are connected, but it's only been in the last couple of decades that this research has really caught up.

One of the current projects in Sarkis' lab is looking at how a molecule made by a gut microbe may be related to anxiety. So most of these studies, up until now, have only been done in mice, but they're starting to move into humans.

KWONG: Walk me through the research.

MCCOY: OK. So there's this molecule that the team focused on. It's called 4-Ethylphenyl sulfate, or 4EPS. So it's made by a human gut microbe. And some studies have shown that kids with autism actually have higher levels of it.


MCCOY: OK. So autism and anxiety can often go hand in hand. And Sarkis' research team wanted to know if they could tease out a potential connection between this molecule, 4EPS, and anxiety in people with autism.

KWONG: Sounds like a very advanced and complicated question to research.

MCCOY: It is. And so before they could study it in humans, they did experiments in mice. And they did show that mice were more anxious with more 4EPS in their circulation and vice versa.

KWONG: Oh, wow.

MCCOY: And what they found in mice with more 4EPS was really interesting. The molecule was actually changing some things in the brains of these mice.


MAZMANIAN: Resulted in changes in the brain and brain physiology, changes in particular cell functions in the brain, and resulted in mice that were more anxious than animals that did not receive this particular microbial chemical.

KWONG: Those poor mice. I know it's for research, but dang. Do they know why this is happening, why this molecule is changing their brain?

MCCOY: Sarkis told me what they know so far is that it changes how neurons communicate with each other. Communication went up in some parts of the brain and down in others, mostly in areas related to emotions. Sarkis has done a small clinical trial in humans. It focused on adolescents with autism, which - again, autism and anxiety often go hand in hand.

MAZMANIAN: We saw improvements in anxiety and we also saw improvements in irritability - irritability or aggression.

MCCOY: And those improvements went away when participants stopped taking the drug.


MCCOY: So the study was really small. It was just 26 participants, and all of them knew they were getting the actual drug, not a placebo.

KWONG: Oh, OK. So people may have felt better or less anxious because they knew they were getting this medicine.

MCCOY: Exactly, big caveat. So the study was basically done to show the drug was safe and tolerated at the doses that they gave it. And now the team is recruiting for a bigger clinical trial.

KWONG: OK. So this is really research to keep an eye on. We have links to it in our episode notes. You can check those out to learn more. Berly, what else are researchers looking into when it comes to our gut?

MCCOY: There's actually a lot of research around Parkinson's disease. So a lot of people with Parkinson's actually have gut issues. And another aspect of this disease is formation of clumps of proteins in the brain. And researchers have noticed that those clumps are actually found in other places in the body.

KWONG: Oh, is the gut one of those places?

MCCOY: It is, yep. What researchers don't know yet is where the clumps first start. But Jay Pasricha, the doctor we heard from earlier, told me about a mouse study.

PASRICHA: If you cut the vagus nerve, the main highway between the gut and the brain, then you prevent those changes of Parkinson's occurring in the brain.

KWONG: But in humans, you can't cut the vagus nerve.

MCCOY: In the '50s and '60s, they did. Doctors used to treat peptic ulcers sometimes by cutting the vagus nerve.

PASRICHA: It's still a little controversial. It's some conflicting evidence. But there are some studies, at least, that show that vagotomy in those patients may have been protective and reduced the risk for the development of Parkinson's.

MCCOY: People are just theorizing about how these clumps may form in the gut first and then either travel to the brain or somehow cause clumps to form in the brain.

PASRICHA: So there is a reasonable amount of evidence that at least some forms of Parkinson's may originate in the periphery, particularly in the gut.

MCCOY: And researchers are also looking at the gut-brain relationship in autism, depression, Alzheimer's disease, even pain perception.

KWONG: So the gut could have, I mean, just much bigger impacts on our health than we've realized, especially our brain health, it sounds like.

MCCOY: Yeah. Yeah, and in ways scientists are really just starting to understand.

KWONG: Berly, one last question. Does this change how we think about our microbiomes, as in the actual microorganisms that live in our digestive track?

MCCOY: I asked both Sarkis and Jay about this - specifically if we should be changing our diets.

KWONG: Yeah.

MCCOY: And they both said we're really far away from understanding how tailoring our diet could work to change our brain. Researchers don't even know how to measure if someone has a healthy microbiome. But Jay says...

PASRICHA: I am confident in the next 10 years we'll begin to unlock some of the secrets of the microbiome that it has kept hidden for thousands of years from us. And a major, although not exclusive, advance in human health will come from that.

KWONG: Has learning all this changed your relationship with your gut in any way?

MCCOY: Yeah. Yeah. It's really made me think a lot more about how what I put in my stomach might affect my brain. And I know that this research is so far away from, like, tailoring our diet, right? But it has made me think more about how much our brain and gut are connected.

KWONG: Berly, I am really glad you brought this on. Thank you so much.

MCCOY: Thanks, Emily.

KWONG: To learn more about Sarkis Mazmanian's study on anxiety, autism and the gut, see our show notes or visit This episode was produced by Berly McCoy, edited by Gisele Grayson and fact-checked by Abe Levine. The audio engineer was Gilly Moon.

MCCOY: Brendan Crump is our podcast coordinator. Beth Donovan is our programming senior director, and Anya Grundmann is our senior vice president of programming.

KWONG: I'm Emily Kwong.

MCCOY: And I'm Berly McCoy.

KWONG: And thank you for listening to SHORT WAVE, the daily science podcast from NPR.


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