...if your gut can really talk to your brain? (with Ryan Rampersaud)

Perry Roth-Johnson: 0:06

Hello, this is Ever Wonder? from the California Science Center. I'm Perry, Roth Johnson. Have you ever wandered the yogurt aisle in the grocery store and stumbled upon yogurt or other foods with a label probiotic? These foods claim to support your gut health or your gut microbiome, and some even go so far as to say they can help your mental health. Although that last claim is mostly just marketing hype, some scientific experiments have connected. What's going on with bacteria in the gut to the brain. Scientists have even started to show that people with depression have different gut microbiomes than people without depression. Now scientists still have a ton of questions, but ever wonder if your gut can really talk to your brain. Dr. Ryan Rampersaud is a professor of psychiatry at UCSF. He's also an MD PhD, meaning he is both a medical doctor and a scientific researcher. He and his colleagues are trying to better understand the link between the gut microbiome and depression. He broke down how your gut might be able to affect what goes on in your brain and how much more there still is to learn. Ryan Rampersaud. You are an assistant professor of psychiatry at UCSF. Ryan, welcome to the show.

Ryan Rampersaud: 1:27

Thanks. Thanks for having me.

Perry Roth-Johnson: 1:28

Yeah. And Jenny Aguirre, producer and co-host of the show is here with us again. Hi Jenny.

Jenny Aguirre: 1:33

Hey Perry and hi Ryan. Thanks for joining us.

Perry Roth-Johnson: 1:34

Ryan. So I know you study the gut microbiome and mental health specifically depression. Uh, but before we dive into that, what exactly is the gut microbiome?

Ryan Rampersaud: 1:45

So I think about the gut microbiome as the kind of complex soup of microorganisms and bacteria that live inside your gastrointestinal tract. And so that includes things like bacteria, yeast, viruses, archaea, which is a particular kind of, uh, organism. Um, and all of those things are kind of swimming around in there. Kind of communicating with each other and communicating with the host, um, to do important functions, like digest things, um, but can also kind of go wrong at times, like in the context of having like a diarrheal disease, for example,

Perry Roth-Johnson: 2:24

And when we're talking about the digestive tract, that's like, that's like our intestines and like everything from our mouth to our butt.

Ryan Rampersaud: 2:33

Exactly.

Perry Roth-Johnson: 2:34

Yeah.

Ryan Rampersaud: 2:34

So there's a microbiome attached to every surface of the body. And so the oral microbiome is present and then you have something in the, in the digestive tract. And even along the digestive tract, there might actually be differences, right? So the stomach looks different than the small intestine looks different than the large intestine.

Jenny Aguirre: 2:53

The microbiome is. I'm trying to picture it. It's, um, kind of like the earth and then like all the, like the bacteria, the fungi, the archaea that's like the animals, the humans, everything that's inside the, the earth kind of?

Ryan Rampersaud: 3:07

So the earth in this, in this example, right, the earth, the earth is the same as your, in your intestines.

Jenny Aguirre: 3:14

Right?

Ryan Rampersaud: 3:14

It's the place.

Jenny Aguirre: 3:15

Uhhuh

Ryan Rampersaud: 3:16

And then the bacteria they are like, and the yeast and the archaea and the viruses, it's like the people that live on the earth...

Jenny Aguirre: 3:24

And there's good ones and there bad ones.

Speaker 2: 3:26

...and there's good ones and there's bad ones.

Jenny Aguirre: 3:29

Um, let's dive into your study. So your, your recent study, you are studying the connection between depression and the gut microbiome. Why don't you tell us a little bit more about your study?

Ryan Rampersaud: 3:41

So I think one, one place to start is to take one step back, uh, out of depression and just think about health and disease. And in recent years there's been a lot of work from all different kinds of people, really, really amazing, amazing scientists, really starting to highlight the fact that what lives in your gut right, actually affects human health in a variety of ways. And that includes altering the immune system. Like you heard about before, it includes diseases like, uh, in it includes infections, like things that seem, you know, common sense. And then also even things like diabetes and high blood pressure and hypertension and cancer even, right. All of these things are, are connected to the gut microbiome. And what's exciting from our perspective is the connection between the gut and the brain and how the gut health might be related to depression in some way. And that field is really, really just beginning. And so what we wanted to do was really kind of sink our teeth into this subject and ask, well, how is it that they're connected? Mm- hmm. Right? There have been lots and lots of studies that have said, you know, in depressed people, there's a difference, a depressed person's got microbiome looks very different than a healthy person's microbiome, but we don't really understand exactly what that means yet. And so part of what we wanted to do with our study was really ask that question of like, well, why does it matter that it's different? What does that mean for the person and how is it that a change in the bacterial composition then relates to how someone behaves and how they feel. Mm-hmm. Right? Doesn't seem like it's totally connected, but that's why we, that's why we do science.

Perry Roth-Johnson: 5:29

Wow. That just opens up a lot of questions, but I think a basic one, maybe how can the stuff in your gut change what's happening in your brain? Like I get that we've observed differences, but do we know how that mechanism works yet?

Ryan Rampersaud: 5:42

That's where we are right now. And does it feel right? We are starting to that's the fun part, right, right. Uh, cuz now we're starting to dig into it and ask, well, well, how right we got, we have, we definitely know that there is a difference mm-hmm and so we're starting to understand for just scratching the surface. I think, um, in understanding how it is that things that are in the intestine that are physically separated by a fair distance, doesn't matter how tall you are. Uh by, by a fair distance and a number of like physiological barriers, right? How is it that they could be communicating? And the way that we think about it is that there's probably multiple routes. You will have heard a little bit already about how the microbiome can affect the immune system. Mm-hmm and it's very possible that that's one route, right by which the change in the gut microbiome affects the brain by changing the level of inflammation somebody might experience in their body m m-h mm. And we know from lots of studies from, you know, over t he, over the past decades, that inflammation is linked to the development a nd severity of depression in some way.

Perry Roth-Johnson: 6:50

Okay.

Ryan Rampersaud: 6:50

So that's one potential mechanism. There's also a very long nerve that goes directly from the brain all the way into your gut and it's kind of, is it sort of projects into the gut and kind of takes a, takes a reading. It sort of is saying like, hey, what's, what's the feeling down in the gut. Right? And it can respond to maybe all of the things that the gut produces, all of the things that the gut bacteria produce and can then signal back up to the brain and how that relates to behavior is still a question that remains to be kind of understood. But that is definitely one way in which there might be a, uh, a route of communication. We have lots of studies from animals that suggest that it's actually a really important way that things that happen in the gut get communicated to the brain. I, I like to say that, like, you know, what happens in the gut doesn't stay in the gut. Uh, ala Vegas, right?

Perry Roth-Johnson: 7:43

Yeah. Ok.

Ryan Rampersaud: 7:44

So that's, y ou k now, that's a second way. And then t he other third way amongst other potential routes that we are really interested in is that is the, is the stuff that bacteria produce. And so, you know, we talked a little bit about the fact that the bacteria a re kind of in your gut and they're there, right? But just like the people on the earth, like you mentioned, right. They go to work, they do some stuff. They go out and have fun with friends, right t here, there's all this activity happening. And as t he consequence of this activity, right, they take all t he stuff that you eat and all the stuff that your body produces and they transform those things, right. They make these metabolites that can come out of the gut and go into the bloodstream and from the bloodstream kind of float around and eventually get up to the brain. N ow, not everything that gets into the blood gets into the brain, but there might be a number of things that are produced by the bacteria. And so, u m, that's the other really big, I think the other really major important pathway for how something that happens in the gut, like producing a metabolite or a signaling molecule, mm-hmm, how that might get to the brain to do something. And we still need to understand like what the target is for those signaling molecules m m-hmm and how the activation of a receptor in the brain, biosignaling molecule changes someone's behavior. U m, but the first step is to begin to understand that language, that chemical language of how the bacteria might communicate with the body to begin to understand like how it might affect behavior. Those are three ways m m-h mm potentially,

Perry Roth-Johnson: 9:21

But you guys are studying the third way?

Ryan Rampersaud: 9:22

We're studying the third way. And we're also studying the immune system Uhhuh. Um, and so, and, and I don't know that they're totally disconnected I've, you know, for the purposes of, of my own understanding. Yeah. I separated them out, but in reality, right, they're probably all sort of like mixed up together Uhhuh. Um, but we really think about those chemical signals. That's really important to us to understand the mechanisms by which changes in the gut correspond to changes in the brain. And if we can decode that signal, right. If we can decode that language, we get closer to being able to leverage some of that for like therapeutic benefit. Right? Mm- hmm, if you can understand what they're saying, then you can insert yourself into the situation.

Perry Roth-Johnson: 10:13

Right.

Ryan Rampersaud: 10:13

Right?

Perry Roth-Johnson: 10:14

So you're like, maybe this is a, is a weird way to think about it, but you're like trying to make the spies that can listen in on the conversation that the microbes are having with your brain. Like you're, you're like the microbe NSA, you're trying to figure out, you're trying to decode the message, figure out how it's floating through the blood, to the brain and getting translated into something. That's making somebody feel a different mood. Do I have that sort of right.?

Ryan Rampersaud: 10:39

Yeah. I, I think that makes total sense. Right? It's like code crackers. Mm- hmm. Right? Who are like work for the government who are trying to like decode secret messages. Right? You don't know what they're saying, but they're definitely saying something. And then, so then we wanna say, well, well we wanna be in on that too. Right. We wanna know, we wanna know what the joke is like, what's happening. What are they saying to each other? And in doing that, right. You can ask in, you know, in the context of our study, we can ask, well, this is what it looks like when you're healthy. Mm. And then this is what it looks like when you're depressed. What's the difference.

Perry Roth-Johnson: 11:15

Right.

Ryan Rampersaud: 11:15

Right? And you can kind of say, oh, this is a thing. This is a signal that's not so great. Or this is a signal that is good. And we lost it in a depressed person. And then you can start to, you can take that signal and then start to study it more in depth and then say, Hey, where does that signal go? And who's at the other end listening and what do they do in response to the signal that they get. But first step is to crack the code and understand what the signals are and what they, what they mean.

Perry Roth-Johnson: 11:44

Very cool. Very cool.

Jenny Aguirre: 11:46

What do you and your colleagues hope to find out from this study specifically? Like what's the, what's the goal of this study?

Ryan Rampersaud: 11:52

So I think science is incremental. Um, and we're always kind of pushing to just ask, you know, one specific question and get a little bit of an answer, but then there are also loftier goals. Right? And so I, I think maybe the way to answer that question is to sort of say, is to take the first, the first sort of step, which is to say, what's the smaller question we're asking. And the smaller question we're asking is about a specific class of metabolites produced by the bacteria and whether or not it's different between depressed people and healthy people. And we have a little bit of an indication from some other studies that these molecules that were, that are called indoles, um, that are produced by the bacteria of metabolizing things that come from your diet. Um, we think that they're actually really, really important, um, and that they signal to the brain and they do kind of important things for, uh, the development of depression. And so our, our main question is whether or not is one, is it different? Two, what are the bacteria that are responsible for producing those molecules and then three who's at the other end listening and how does the, how does signaling via that molecule change the activity of a cell in the brain? The bigger question though, is how do we help people with depression? Right? And I think, you know, part of what we are really hoping for is, um, and maybe I'll take a step back for a second to say, you know, depression treatment, hasn't changed for a very, very long time and it's not fantastic, right? There are still, there's still a fair number of people who start treatment and don't have, you know, don't necessarily get the full benefit of, you know, traditional therapies. And so part of what we want to do is start to ask questions about what are other ways that depression comes about that have nothing to do with the therapies that we're already using, right? What's the what's contributing to development to, to depression. And so part of what we wanna do is highlight this new mechanism potentially that contributes to the development of depression. Right? And then the other hope is, could we turn this into a treatment? Right? So could we take the, the understanding of the chemical signals that are good and bad that relate to depressive symptoms? And could we make a probiotic, which I'm sure you've got, you've all seen in the grocery store.

Perry Roth-Johnson: 14:23

Yeah.

Ryan Rampersaud: 14:23

Right? Could we make a probiotic that could be useful. Right? For treating depression mm-hmm um, because if we understood what they did, we could make like a more targeted probiotic. We could say, you know what, people who have depression, they don't have so much of this indole. We should give it back to them. Let's make a, let's make a probiotic. That makes lots of indole, so we can give it to them so that they can feel better.

Perry Roth-Johnson.: 14:51

So, is the dream like to make fancy yogurt that has that indole inserted into it? That you could eat to like, feel less depressed, is that the dream?

Ryan Rampersaud: 15:01

Or a bacteria? Yeah. Or a bacteria that, that naturally produces that. Right? Because if you can, part of, you know, part of the question is like, if you took a bacteria in. Right? Like a probiotic mm- hmm, could you have it take hold and restructure the, the gut microbiome changes that are happening. Right. Um, so adding the thing that's beneficial is great, but it may not be long lasting.

Perry Roth-Johnson: 15:27

Oh, okay.

Ryan Rampersaud: 15:27

But if you did a probiotic, right. Then it's like, it's like the, the gut microbiome is now changed. Right?

Perry Roth-Johnson: 15:35

Yeah.

Ryan Rampersaud: 15:35

So it went from being this like microbiome. That's not so great. But then you gave a probiotic that then kind of shifted the composition and changed the activity. And that's a more long lasting solution. Right? Mm-hmm.

Jenny Aguirre: 15:48

The aliens are conquering the earth. That's all I thought of a nd they're gonna make it better.

Ryan Rampersaud: 15:55

But they're helpful.

Jenny Aguirre: 15:55

They're yeah. And they're gonna make it better. That's what I pictured.

Ryan Rampersaud: 16:00

They're helpful. They're not, they're not, they're not sucking out all the resources from this planet.

Jenny Aguirre: 16:03

I have been going on a sci-fi like binge lately. So all I could think of is aliens in space right now.

Ryan Rampersaud: 16:11

It's a good analogy though, right? Like, yeah. It's, it's something foreign that's coming in.

Jenny Aguirre: 16:16

Yeah.

Ryan Rampersaud: 16:16

And changing something, but it's not independence day, right? Like they're, they're not doing bad.

Jenny Aguirre: 16:21

No, these are nice ones.

Ryan Rampersaud: 16:23

It's a good job.

Jenny Aguirre: 16:23

No Independence Day, no Mar's Attack. This is, this is nicer.

Ryan Rampersaud: 16:27

That's right.

Perry Roth-Johnson: 16:27

Totally.

Jenny Aguirre: 16:30

All right, Ryan. So let's just try to think into the future in the next 10 years, what discoveries do you hope people will make in your field?

Ryan Rampersaud: 16:41

Hmm. Yeah. Um, so in this field, which is really, really new right. Of gut brain access signaling, um, there's still a lot to know. And so I think maybe I'll take the same approach that I did with my, with the previous question, which is little goal, big goal.

Jenny Aguirre: 17:01

Big goal.

Ryan Rampersaud: 17:02

And, and so little goal. Right? I hope that we are able to decode and understand even just like a 10th of the functions that are important to the development of depression. Right? That are either, you know, that are altered under depressive states. Um, I hope we begin to just like, get just a sliver of that because I think that's a realistic goal. Mm-hmm um, cause it's gonna be, it's gonna be a complicated question. The bigger goal, I would love to see a future where we can treat depression and anxiety and other psychiatric related issues with something like a probiotic that, you know, feels safe and easy and potentially has less side effects. That's the ideal situation.

Jenny Aguirre: 17:57

That would be amazing.

Ryan Rampersaud: 17:58

That's like you know high in the sky kind of aspirations.

Jenny Aguirre: 18:00

Yeah. That would be amazing. Yeah. That, that would be great.

Ryan Rampersaud: 18:05

But I think the, the most important thing is that, you know, what do I wish for? I just hope that we understand things a little bit more. And I think that's the, you know, that in and of itself is a huge, is a huge, uh, benefit to the world.

Perry Roth-Johnson: 18:19

Right. Spoken like a true basic science researcher. I just wanna know how it works.

Ryan Rampersaud: 18:25

I just wanna know how it works.

Perry Roth-Johnson: 18:26

I don't need to make fancy yogurt yet. I just wanna know how it works.

Jenny Aguirre: 18:32

What's going on. Yeah.

Ryan Rampersaud: 18:33

That's the fun. Right, right. When you can just like, you can ask the question and then you, and then, you know why it works the way it works, you know, about like the internal, like engines, the parts that are happening, you know, inside under the hood. Mm-hmm

Jenny Aguirre: 18:47

Well, if, if you think about it though, like that's, that's the big chunk of moving forward, you have to know what's going on. And once you do, then, you know, whatever comes afterwards, the fancy yogurt or the different probiotics, those are gonna be easier to create.

Ryan Rampersaud: 19:03

Exactly. Yeah.

Jenny Aguirre: 19:04

I think it's your line of work is pretty intense and pretty fascinating just because that that's a lot, a lot, you have to look at different types of people, different ethnicities, different age groups, different and every single person is different, so, yeah.

Ryan Rampersaud: 19:23

Yep. But there's someone out there, some brilliant person who's gonna take. Right? This is how science works. That's gonna take the knowledge that somebody else developed and run with it and do something really, really amazing. Mm- hmm. Right? And if, you know, if I can contribute even just a little 1/10th to the knowledge that exists currently, we're in good shape.

Jenny Aguirre: 19:44

Right. It'll spark that little light bulb in somebody.

Ryan Rampersaud: 19:48

Absolutely.

Perry Roth-Johnson: 19:50

When you're talking to people in your work, like maybe your subjects, you know, who are in the study, do you notice, uh, any patterns like where people might have a misunderstanding about the gut microbiome and how it works? Is there anything you wish more people knew?

Ryan Rampersaud: 20:04

I think that people can swing in both directions. Mm- hmm some people will say that's not a thing. And then some people will say, it's the only thing. Mm. Um, and it's the most important thing. And, and we have to, you know, how can I use a probiotic to treat my depression? And I think we have to help people get back to the to the middle. Mm. Which is, it's definitely related. There's, there's definitely a connection, but we don't know enough yet. And I think the question that I often get is this is great. So what do you, you know, what should I take? What should I get at the groceries...

Perry Roth-Johnson: 20:39

Right.

Ryan Rampersaud: 20:39

...store? And, you know, I wish that I had the, an answer that said, you should take this. This is perfect for you. Um, but the reality is is that we we're not there yet. And so I think, you know, the thing that I often tell people is we're getting there, but we still have a long way to go. And so keep an eye out, keep your hopes up. We'll get there eventually. But it's hard to say that this is, you know, this is the, the absolute end, all be all answer to what's, you know, what's ailing you at the moment.

Perry Roth-Johnson: 21:10

Right, right. Isn't that, so it's so interesting, but also frustrating at the same time that science is that way. It's a lot of gray and people want very clear answers, but it's a lot of gray for a long time until there's like consensus. Uh, and I see we're running out of time, Ryan. So where can people follow you online and find your work if they want to learn more?

Ryan Rampersaud: 21:33

Oh, um, that's a good question. And very much, um, not connected as of yet, but, uh, we do have our, our website, which is our study website, which is cand.ucsf. edu. Um, and there, you can get information about the study and then hopefully in the future, um, we'll get on the Twitter bandwagon we've started and we're gonna, we're, we're working our way. We're working our way up to it. I'm still very much like an old fashioned person in that way.

Perry Roth-Johnson: 22:02

It's probably a good thing. I mean, let's be honest especially if you're on zoom all the time, like you need a break from the internet. Well, it has been wonderful talking to you, Ryan, thank you for breaking, uh, the microbiome down and, and putting up with our, our silly, uh, metaphors. Thank you for joining us on the show.

Ryan Rampersaud: 22:21

Thank you. And I think your metaphors are fantastic. They make so much sense. And I, you know, just to sort of acknowledge like science is for everyone. And I think this is the way that, that it gets communicated, real language metaphors that make sense aliens invading planet earth.

Perry Roth-Johnson: 22:42

That's our show. And thanks for listening until next time. Keep wondering, Ever Wonder? from the California Science Center is produced by me, Perry Roth-Johnson, along with Jennifer Aguirre, Liz Roth-Johnson is our editor. Theme music provided by Michael Nickolas and Pon5. We'll drop new episodes every other Wednesday. If you're a fan of the show, be sure to subscribe and leave us a rating or review on Apple Podcasts. It really helps other people discover our show. Have a question you've been wondering about? Send an email or voice recording to everwonder@californiasciencecenter.org, to tell us what you'd like to hear in future episodes.