03/27/2020

Mapping The Microbiome Of Your Tongue

17:14 minutes

Your mouth is home to billions of bacteria—some prefer to live on the inside of the cheeks, while others prefer the teeth, some the gums, or the surface of the tongue. Writing this week in the journal Cell Reports, researchers describe their efforts to map out the various communities of bacteria that inhabit the tongue. 

In the average mouth, around two dozen different types of bacteria form tiny “microbial skyscrapers” on your tongue’s surface, clustered around a central core made up of individual human skin cells. The researchers are mapping out the locations of the tiny bacterial colonies within those skyscrapers, to try to get a better understanding of the relationships and interdependencies between each colony. 

Jessica Mark Welch, one of the authors of the report and an associate scientist at the Marine Biological Laboratory in Woods Hole, Massachusetts, talks about what we know about the microbiome of the human mouth, and what researchers would still like to learn.

a human tongue that has been imaged, resulting in patches of various colors over certain regions of the tongue.
Bacterial biofilm scraped from the surface of the tongue and imaged using CLASI-FISH. Human epithelial tissue forms a central core (gray). Colors indicate different bacteria: Actinomyces (red) occupy a region close to the core; Streptococcus (green) is localized in an exterior crust and in stripes in the interior. Other taxa (Rothia, cyan; Neisseria, yellow; Veillonella, magenta) are present in clusters and stripes that suggest growth of the community outward from the central core. Credit: Steven Wilbert and Gary Borisy, The Forsyth Institute

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Segment Guests

Jessica Mark Welch

Jessica Mark Welch is an Associate Scientist at the Marine Biological Laboratory in Woods Hole, Massachusetts.

Segment Transcript

IRA FLATOW: This is Science Friday. I’m Ira Flatow. You know when you go to the doctor for a regular checkup? What’s one of the first things that happens? Stick out your tongue and say ah, right? But when you do stick out your tongue, you know you’re not just showing off one of your body’s more useful muscles? You’re also showing off a collection of billions of bacteria that make their home within your mouth.

Researchers are trying to map out exactly what lives in your mouth and where, hoping that the information could provide clues to health and disease. And writing this week in the journal Cell Reports, a team of researchers has taken a first taste at mapping relationships between the bacterial colonies that live on the human tongue. SciFri director Charles Bergquist spoke with Jessica Mark Welch, an associate scientist at the Marine Biological Laboratory, one of the authors on that study.

CHARLES BERGQUIST: Thank you for joining me.

JESSICA WELCH: A pleasure to be here. Thank you.

CHARLES BERGQUIST: Let’s talk about what’s going on in the environments in your mouth. Are all mouth bacteria the same?

JESSICA WELCH: There a lot of different bacteria that live in your mouth. And in fact, there are different kinds of bacteria that live on your teeth and on your tongue and on your gums and on your cheek cells. So all the different environments in your mouth have different bacterial communities that live on them.

CHARLES BERGQUIST: In this particular study, you were looking specifically at the tongue. How are the bacteria arranged there?

JESSICA WELCH: The bacteria on your tongue build these little skyscrapers. They build these little microbial apartment buildings. When we looked at them through the microscope, we said, wow, there’s so much more structure there than we’d expected. It was really amazing.

CHARLES BERGQUIST: Is it just bacteria stacked up on top of bacteria? Or are they glommed on to some, I don’t know, support structure?

JESSICA WELCH: So the bacteria on your tongue, they’re arranged on your tongue epithelial cells. So there’s a core cell at the center of these clusters of bacteria that’s human. And onto that human cell, these bacteria grow. And they grow out in little clusters. And different bacteria live in different places in the clusters. So there are some bacteria that seem to like to live right down in with the human skin cell, the human epithelial cell that’s on your tongue. And then there are other bacteria that form a crust on the outside and others that form clumps in the middle. So it’s a really very complex, complicated structure.

CHARLES BERGQUIST: You’re developing a map of how the bacteria are organized vertically in those skyscrapers, you mentioned. It’s sort of who’s living on what floor and who’s next to the laundry room and all that?

JESSICA WELCH: Yeah, exactly. What we want to know is how are the bacteria arranged relative to each other at these really fine scales, these micrometer scales, so 1,000th of a millimeter. Which bacteria are next to who? Which are which bacteria next to which other bacteria? Which are right next to the human cells? And how do they arrange themselves?

CHARLES BERGQUIST: So this isn’t a map of the tongue in terms of who’s living on the tip of the tongue versus the sides of the time versus–

JESSICA WELCH: Exactly. What we were interested in was really the fine scale structure at the bacterial scale, the scale at which the bacteria are really living and interacting with each other. What’s the structure and what’s the map there?

CHARLES BERGQUIST: Looking at the pictures in the paper, it doesn’t look like there’s a ton of large scale patterns or organization. Does it really matter who’s living where?

JESSICA WELCH: So the reason it matters is that bacteria interact with whatever’s right next to them. So the bacteria are taking up nutrients, and then they’re secreting other nutrients. They take up molecules and secrete molecules. And they do that most dramatically, most importantly with all the bacteria that are right next to them. And the bacteria that are right next to the human cells are also in the best position to influence human cell biology.

CHARLES BERGQUIST: Are these bacteria living on what we would call the taste buds? Or are they influencing how we– the flavors we’re experiencing?

JESSICA WELCH: So if these clusters of bacteria that we see aren’t right on the taste– they’re certainly right next to the taste buds. And it’s certainly possible that exactly what kind of bacteria you have on your tongue influences how you taste food. Now, on the other hand, the food comes through your mouth really quickly, just in a few seconds. So the bacteria would have to be acting pretty fast to make a difference for your taste.

CHARLES BERGQUIST: The food’s moving through my mouth, the saliva is sloshing around, what’s keeping the bacteria in place? Is there some kind of glue or, I don’t know, tendrils or something that they have?

JESSICA WELCH: Yeah, exactly. So all the bacteria that are in your mouth, they have to be hanging on to something, or else they’re going to end up in your stomach. And they don’t want to be in your stomach. They want to stay in the mouth. So every bacteria in your mouth is adhered to something. It’s either adhered to your cells or to your teeth or it’s adhered to other bacteria that are hanging onto your teeth.

We ask our volunteers to basically just clean their tongues. And then we collect the stuff that they’ve scraped off their tongue. And we look at it under the microscope, and we see these clumps and clusters that stick together really pretty well through all of our experimental manipulations. Because they’re sticking together in the mouth with the way they grow.

CHARLES BERGQUIST: So the volunteers are using one of those tongue scraper things that some people use for oral care.

JESSICA WELCH: Yeah, exactly. They’re just using a little ridged plastic tongue scraper like your dentist might hand you and say, here, you should scrape your tongue.

CHARLES BERGQUIST: And should people scrape their tongues? Do you have any sense of whether it makes a difference?

JESSICA WELCH: So when you scrape your tongue, it certainly reduces the number of bacteria in your mouth. And that does seem to be a good thing. You can’t get rid of all of them. There’s always more of them coming up behind. But when you scrape your tongue, the same as when you brush your teeth and floss your teeth, can you can reduce their numbers. And that’s probably good.

CHARLES BERGQUIST: What about mouthwash?

JESSICA WELCH: So the interesting thing about mouthwash and the bacteria on the tongue and in the rest of the mouth is that using mouthwash seems to have an effect on your blood pressure because of the bacteria. So what these bacteria can do that your body doesn’t do very well is they take a certain nutrient that’s in your food. It’s called nitrate. The bacteria can convert nitrate to nitrate, which your body doesn’t do very well.

Then your body takes the nitrate and turns it into nitric oxide. And that has a lot of effects, including regulating your blood pressure. So the interesting finding is– and this is other people’s work, it’s not our own– is that if you eat a diet that’s rich in green leafy vegetables and other healthy foods, that will lower your blood pressure by a little bit, small but measurable amount, but not if you’re using an antiseptic mouthwash. So the bacteria are an important part of that effect of the healthy diet.

CHARLES BERGQUIST: So wait, using mouthwash can alter my blood pressure, with all those other things taken into account?

JESSICA WELCH: Yes. So all those things taken into– yes. So there have been scientific studies where people have shown that, yes, if you consume a high nitrate diet and then use mouthwash, that will alter your blood pressure just a little bit.

CHARLES BERGQUIST: Zooming out from just the tongue, how many different species of bacteria are in an average mouth?

JESSICA WELCH: There are about, oh, a couple hundred species of bacteria in the average mouth. There are about 500 species of bacteria, 500 or 700, that are known from the human mouth as a whole in all the people all over the world. Only one person has maybe a couple hundred.

CHARLES BERGQUIST: And how much do different people have in common? How similar are my mouth bacteria to your mouth bacteria?

JESSICA WELCH: What we’ve found, and this is something we’re learning only just recently, what we found is that different people have pretty much the same species of bacteria. So we all have pretty much the same species. And in fact, the bacteria on your tongue are the same as the bacteria on my tongue, the bacteria on your teeth are the same as bacteria my teeth pretty much.

But we all have slightly different proportions of those bacteria. So somebody will have a lot of one kind, somebody else will have a lot of another kind. And we also have slightly different strains of bacteria. So if I take a sample from your mouth and then, a year later, you come back, I can identify you– at least I could pretty much guess which person you are based on what bacteria I find in your mouth.

CHARLES BERGQUIST: So you could actually– I mean, would this be a reliable forensic technique? Could you identify somebody based on, I don’t know, scraping off their tongue?

JESSICA WELCH: It’s certainly not as reliable as your genome would be. But one could certainly make a good guess based on the bacteria that you have, your specific strains of bacteria.

CHARLES BERGQUIST: You’re developing this map of the bacteria that are there. And I guess there are people that are working on the microbial census of the mouth. Do we have any sense yet of what is healthy, what is normal, what is a standard mouth?

JESSICA WELCH: We’re starting to get a sense, I think, of what’s the range of normal that you find in the mouth. The Human Microbiome Project did a lot of DNA sequencing from the bacteria in the mouth. And they’ve shown what bacteria tend to be there. So what we’re still working on on the imaging side is finding out what kinds of structures are normal. What’s the range of normal in the structures of bacteria that you see in the mouth?

CHARLES BERGQUIST: What does that get you? I mean, what’s the goal in knowing that information?

JESSICA WELCH: So the goal really is to be able to understand how the bacteria work, how these communities work. First of all, why are there so many different kinds of bacteria? Why aren’t there just two or three or four? Why do we have hundreds? What are they all doing in the mouth? We know that some people’s microbiome, some people’s sets of bacteria, can work well for them, seem to promote health.

But then other sets of bacteria, other microbiomes, can cause disease or can contribute to disease. And we’d like to understand, what are the characteristics of a healthy microbiome? What are the characteristics of disease? And then really, the ultimate goal is to be able to shift the microbiome from a disease state into health.

So if we can really understand how these bacteria work together, then we can understand what conditions the good bacteria need to grow. So the reason to look with imaging is to see exactly what environment a good bacterium needs to live in. Who does it have to be next to? And then how can we tweak the environment, tweak the community to push it toward health?

CHARLES BERGQUIST: Are these things that grow in a Petri dish, can you do some of these experiments, what nutrients do they need, what other supports do they need, in the lab?

JESSICA WELCH: Yeah. So one really interesting thing about bacterial communities that we’ve been learning is that, if you go out and sample bacteria from the soil, say, or from the ocean, really only a tiny fraction of them will grow on your Petri dish in the lab. They need something that we don’t know how to give them. And probably, they need to be next to some other bacterium that we don’t know what it is.

That’s another reason we want to do the imaging and find out who’s next to who. In the human mouth, it turns out that about half of the bacteria can be grown in a Petri dish. And for those other half, there is probably, again, something that they need or somebody that they need to be next to that we don’t know yet. So that’s one of the things we’re trying to learn.

CHARLES BERGQUIST: I can’t help but notice you’re at the Marine Biological Laboratory. What relation do tongues have to do with marine life?

JESSICA WELCH: That’s a great question. We do a lot of really basic biological research at the Marine Biological lab. So we started using the giant axon of the squid to ask questions about neurobiology, using the great big oocytes in surf clams to ask questions about cell division. So what we’ve really been about for more than 100 years is using these marine model organisms to ask basic science questions.

But because of that, we have a lot of innovative microscopy that you can really see put to work in this project. And then we also have a lot of experts who study bacterial communities anywhere in the world, in the Arctic, in the deep sea, in coastal marshes. And here, we’re just applying that to an environment that’s a little bit closer to home. And then I’m doing that with my colleagues at the Foresight Institute, who are real experts in oral microbiology as well.

CHARLES BERGQUIST: Are there marine organisms that have tongues that you’ve looked at?

JESSICA WELCH: [CHUCKLES] That’s a good question. There are marine organisms with tongues. And I haven’t looked at them yet, but I’d love to. I’d love to find out where else besides the human mouth you find such fantastic structures, those amazing bacterial structures that these bacteria build.

CHARLES BERGQUIST: You’re listening to Science Friday from WNYC Studios. I’m Charles Bergquist, talking with Dr. Jessica Mark Welch from the Marine Biological Laboratory at Woods Hole. We’re talking about tongue bacteria. When I go to the dentist and I leave with those nice, clean feeling teeth, how long does it take for them to get recolonized by the bacteria communities in my mouth?

JESSICA WELCH: Minutes. So when the dentist cleans your teeth, your teeth are really pretty clean. The dentist do a great job of getting all the bacteria off, at least 90% of the bacteria. But then within seconds, your nice, clean enamel of your teeth gets coated with saliva. There’s a coating called the salivary pellicle that goes onto the enamel and a different coating called the mucosal pellicle. It goes on your tongue and your cheeks.

And bacteria, within minutes, start attaching to that pellicle. Bacteria start reattaching to your teeth. And there are initial colonizers that are really good at binding to those pretty clean teeth with a little coating of saliva. And then there are other bacteria that come in and bind to the initial colonizers. So it’s a whole ecological succession, really, going on in your mouth. And actually, it goes on every time you brush your teeth every day.

CHARLES BERGQUIST: And when bacteria start to colonize apart, is it just sort of luck of the draw who happens to get into that niche first and start multiplying and growing outwards? Or are there ones that really like the squishy places and other ones that like the not so squishy places or some other environmental variable that they’re looking for?

JESSICA WELCH: So some bacteria are really good at attaching to that first salivary coating on the teeth. So to some extent, it’s which bacteria are particularly good at being the first colonizers. But then there is also probably a lot of chance involved. So for these structures on the tongue, when a new piece of human tongue cell becomes available in the mouth, when it shows up in the mouth to be colonized, whichever bacteria land on it first probably have a pretty big influence on what kind of community grows out over time.

CHARLES BERGQUIST: Where else are you planning to go with this? Do you want to develop a map of what lives on my tip of my tongue versus the sides? Or is that not of interest? Or what other directions do you have for this?

JESSICA WELCH: So we’d love to know what kinds of bacteria live exactly where on your tongue and what kinds of structures we see if you look at the very back of the tongue or in the crevices between the papillae versus on the front of your tongue or the sides. We’d also really love to push this forward to looking at the dynamics of the community. So so far, everything we’ve looked at, we’ve had to take the sample out and fix it. It’s all dead. We’d love to be able to watch these bacteria growing and see how they grow, how they accrete. I think that’ll tell us a lot about how they’re working together.

CHARLES BERGQUIST: And how would you go about doing that? Is it looking at, I don’t know, cadaver tongues or peeling pieces of tape off my tongue surface? Or what are you doing?

JESSICA WELCH: Right. So yeah, to discover how the bacteria are arranged on the tongue, it would– so the simplest thing we can do is just take little scrapings from all over the tongue and look at them. We have certainly thought about trying to get cadaver tongues or to put tape on the tongue and peel it off and see exactly what’s where. We’ve also thought about going to piercing parlors, where people are having their tongues pierced, and collecting those samples.

This is all in the future. We haven’t tried this yet. And for the live imaging, to image these microbial communities live, we’d really have to change the whole way that we’re labeling them. So it’s another whole transformation of how we’re doing the science. But we’re really excited to try to push the microscopy in that direction.

CHARLES BERGQUIST: It’s tough to paint fluorescent probes all over somebody’s tongue.

JESSICA WELCH: Yes. We have a little trouble getting permission to do that from our human subjects review board.

CHARLES BERGQUIST: Well, thank you very much for taking the time to talk about it with me today.

JESSICA WELCH: Thank you so much. It was a pleasure.

IRA FLATOW: That was SciFri director Charles Bergquist speaking with Jessica Mark Welch, associate scientist at the Marine Biological Laboratory in Woods Hole.

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