From Leeuwenhoek to Today: Unveiling the Secrets of the Oral Microbiome

Intro and Outro: Hello, and welcome to the Microbiome Medics Podcast. Intro and Outro: I'm Dr. Siobhan McCormack. And I'm Dr. Sheena Fraser, and we're your co-hosts. Intro and Outro: We are both GPs and lifestyle medics with a shared passion for microbiome science.

Intro and Outro: We'll be translating the evidence and packaging it into actionable, Intro and Outro: bite-sized chunks so that you could harness the power of the microbiome to improve Intro and Outro: your own health and that of your patients. Siobhan: So, hello and a very warm welcome to another episode of Microbiomedics. Siobhan: I am Dr. Siobhan McCormack, and today we have a fascinating topic for you, the oral microbiome.

Siobhan: So, joining me to discuss this subject is a leading expert in the field of oral Siobhan: microbiome research, Professor Egya Zahra from the Academic Centre of Dentistry in Amsterdam. Siobhan: Professor Zahra, welcome to the show. Guest: Thank you for having me here today. Siobhan: So let's get cracking. What is the oral microbiome and why should listeners care? Guest: Well, I think if you give me time, I can keep talking now for hours. Guest: So please stop me when I'm there.

Guest: But I think oral microbiome is the most important microbiome of your body because Guest: that's actually where all the stuff enters your body. Guest: It goes through the mouth and these microbes are there to protect us. Guest: So imagine completely sterile mouths. We would be extremely sick people. Siobhan: Wow. So there is so much for us to talk about here. So you're saying that the Siobhan: oral microbiome is the most important microbiome.

Guest: Well, no, you cannot. No, no, no. Gut is, of course, not secondary to oral. Guest: But I mean, you only hear about gut, gut, gut. Guest: And I would like to say, please don't forget oral, because if you don't have Guest: a good oral microbiome, you will get problems in the gut. Siobhan: I suppose the oral microbiome is an extension of the gut microbiome.

Siobhan: If you think about the gastrointestinal tract going from the mouth to the anus, Siobhan: but we do concentrate on the gut microbiome in the colon area, Siobhan: which is the highest density of bacteria in that area. Siobhan: So how does the gut microbiome compare to the oral microbiome in terms of its density of microbes?

Guest: Well, it is very rich. It's actually very diverse, Guest: but there are a lot of microbes at different places in gastrointestinal tract Guest: and most of them we cannot study the oral microbes we can because it's easy Guest: to access and and to to get them out and to put on their microscope like it has been done in, Guest: in the history but oral microbes have um Guest: Hundreds of different species in the same mouse and there are a lot of types

Guest: estimated and not all have been identified so we don't know much about them. Guest: And when I talk about microbes actually most studied are bacteria but there Guest: are a lot of fungi, a lot of archaea and viruses we know hardly anything about. Guest: So it's a huge wealth of microbes. Siobhan: Yeah, well, you spoke about the historical context, and I think it's really

Siobhan: fitting. I'm talking to you, a microbiome scientist from the Netherlands, Siobhan: because we could argue that's where microbiology started with the discovery of oral microbes. Siobhan: Can you tell the listeners a bit more about that? Guest: Yeah, thanks for this. This is really nice because in the 17th century, Guest: Anthony van Leeuwenhoek, who was Dutch, a very bright man, and he made his own Guest: first microscope, a simple microscopic lens.

Guest: And he was playing with it. He took some pond water and looked under the lens Guest: and saw little animals moving. Guest: But he also took his dental plaque. Guest: So he scraped his plaque from his teeth and put under his lens. Guest: And he could see that in a little droplet of water, there were small things moving. Guest: He called them animalcles. So these little animals, he thought they were animals, Guest: but which were certainly bacteria, were moving around.

Guest: And he was trying to kill them with vinegar. Guest: And when he was just flushing his mouth with vinegar, nothing happened. Guest: He couldn't kill these moving things. Guest: But when he removed this biofilm and dispersed it with vinegar outside of his Guest: mouth, then it showed that he could kill them. Guest: So that also showed the first nice principle of biofilm being protected from antimicrobial agents.

Siobhan: Yeah, absolutely fascinating. So how did you get involved in oral microbiome Siobhan: research? What's your career journey to take you to this point? Guest: Well, that's a very weird road I made. Actually, I wanted to become a general practitioner. Guest: But before I started my study, I thought I want to try myself. Guest: How am I doing it? Can I handle hospitals and all the blood?

Guest: And I asked my cousin, who was a hospital doctor, to arrange a place that I can help in a hospital. Guest: And she said, oh, there was no place to help. So only place she could arrange Guest: was at the dental practice. And then I had this summer job. Guest: I was 15 and I was just helping this dentist and I really was like, oh, wow, this is so cool. Guest: And I could also already try little things in the mouth of patients, like assisting.

Guest: And I loved it. So I said, OK, I'm going to be a dentist. Guest: But I didn't think much about it. And when I was a dentistry student, Guest: I realized that it's a lot about handling things. So I was very good with my hands. Guest: And then I was thinking, yeah, so many people take good care of their teeth, Guest: but they still get cavities. So why is this happening?

Guest: So I was more like worrying and thinking, how can we help these people than Guest: just filling, drilling and billing? Guest: So that's how I was searching for a place to do research. And I ended up in Guest: Amsterdam as a PhD student. Guest: And since then, I never left because then I discovered that microbes actually Guest: have a crucial part in these oral diseases. Guest: And well, that's where I'm still there, almost after 30 years still researching it.

Siobhan: Well, I know that the ecosystem of the oral cavity is, you're absolutely fascinated by that. Siobhan: So I want to help the listeners understand how incredible the oral cavity is. Siobhan: So we're going to do an Alice in Wonderland scenario. Siobhan: Imagine we drink a potion that shrinks us down to the size of a flea, Siobhan: and you and I hop into the mouth of some willing participant.

Siobhan: I want you to shine your tiny spotlight on some of the structures in the mouth Siobhan: that maybe people don't think about. Guest: Well, great exercise. Just one little side note. Guest: What age are we? Because when you are born, you don't have teeth. Guest: And then you get teeth. And then, of course, a lot of things change in your mouth. Guest: So when you take my spotlight and come with me into your oral cavity, Guest: it depends on what age I am.

Guest: So imagine I'm just my own age and you come in. Guest: And then we are going there. We first have to pass the lips, Guest: which look like skin, but they're not. Guest: They have a very specific structure. And just inside of our lips, Guest: we have a lot of salivary glands. Guest: So small glands which produce mucus, which makes our lips soft and moist. Guest: And then we also have, of course, teeth we have to pass. And they are in nice row.

Guest: And some of them might have fillings, some not. Guest: And these teeth are covered first with a film from saliva. Saliva is the fluid Guest: basing the teeth and all the surfaces in the mouth. Guest: At Health, we have very rich saliva, which is rich of fluid, Guest: of proteins. It's actually the food source of all the microbes in the mouth. It comes from saliva. Guest: So this film of saliva allows bacteria and attach on these surfaces, Guest: on the teeth and also on mucosa.

Guest: So the cheek, the tongue, the palate. Guest: So it's all called mucosal surfaces, soft surfaces. Guest: These are very unique surfaces in our body because it's the only surface which Guest: is hard and open to outside world. Guest: So that's also like for us hard because we have to remove these things growing on them. Guest: Otherwise, there is no way these would get clean by itself.

Guest: Our mucosal surfaces, so the cheeks, the palate, the tongue, Guest: do get clean by themselves because these mucosal cells desquamate. Guest: They come off when they get older. So the new cells grow and they push away Guest: these bacteria. So that's how we keep our mouth clean. Guest: Okay, then we were traveling from the teeth. We actually fall down on the tongue, Guest: and tongue is really like a jungle. Guest: It's full with crypts, with papillus, with little valleys.

Guest: And all these structures allow us to taste things. Guest: So it's full with taste buds, and these taste receptors are hidden in these structures. Guest: And for them to work, we need to have, again, saliva, which moistures them, Guest: but we also need bacteria. Guest: There's some research showing that to experience taste, you have to have good

Guest: balance. And if your tongue is very thick, coated with a thick, Guest: dark coating, then you also don't taste well because it blocks these taste receptors. Guest: Well, what else do we have then? If we go further, we have a throat. Guest: A throat, you have these tonsils, so that these lymphatic organs catching up Guest: bacteria or viruses, whatever comes into our body. Guest: That's our first line of defense from our immune system.

Guest: Oh, yeah. One thing I should have mentioned, next to the teeth, it's also a crevice. Guest: This crevice, that's the area where the gum meets the tooth. Guest: And in this crevice, also our immune system talks to us. Guest: So there are nitrophils, so immune cells coming out from our bloodstream. Guest: And the serum-like fluid comes there, which also feeds bacteria, Guest: but also protects us. It has a lot of antimicrobial substances.

Guest: Just as saliva. Saliva also has a lot of antimicrobial substances. Guest: So it all kind of keeps this mouse relatively clean, but still allows good bacteria to survive. Siobhan: Wow, this is a really interesting way of viewing it because we have this whole Siobhan: metropolis with these incredible craters and mountains and hills and saliva lakes. Siobhan: And it's much more complex than we think about it normally.

Siobhan: So this is the biome. So now let's meet the microbes. Siobhan: Who's there it's teeming with life this this metropolis tell us something about Siobhan: the the bacteria in particular that's what's been most researched to date.

Guest: Yeah well the bacteria are most researched you know like i said already from Guest: 17th century and back into 19th and 20th century already first cultures from Guest: oral microbes has been done and people focused historically at these easily culturable microbes. Guest: So we know a lot about one type of microbe. It's called Streptococcus. Guest: And the Streptococcus grows easily in a lab. So that's why most of the decades Guest: until the molecular methods came,

Guest: people thought about this quite simple system. Yes, you can culture it. Guest: There are, of course, also other bacteria you can culture which grow in more Guest: difficult conditions. They don't grow under oxygen. Guest: So those are the ones which are also producing smelly products. Guest: You can smell them in the morning breaths or you can have them sitting in your tongue.

Guest: And if you have this thick coating I just spoke about, then you could also smell Guest: these bacteria making these sulfur-rich products. Guest: So those are the ones we don't like to have in big quantities. Guest: But the healthy oral microgram is usually having these pioneering communities. Guest: So the streptococcae, actinomyces, so bacteria which attach to clean surfaces.

Guest: And they really are not afraid of oxygen. But the older your biofilm in the Guest: mouse gets, the less oxygen there is. Guest: And then you can start to get these anaerobic microbes. Guest: Well, there are a lot of microbes we just discovered, like I said, Guest: through molecular techniques. Guest: There are some interesting ones which don't have proper names yet. Guest: Some are like endoparasites or symbiotic parasites.

Guest: They live on top of other bacterium because their own genome is very small and Guest: they lack some enzymes to be on their own. Guest: So it's really fascinating how they manage this. Guest: And then, like I said, besides bacteria, we have also fungi. Guest: Fungi are much larger than bacteria, and they are eukaryotes. So they're like us. Guest: They have cell nucleus, so they also behave differently.

Guest: And they are there. They are in low numbers, but because of their larger size, Guest: they have a relatively large niche in oral cavity. Guest: And they can become nasty if things change. Guest: So we call them opportunistic pathogens, like this candida albicans. Guest: Can result in white thrush in the mouse.

Guest: And then I also mentioned viruses. So, of course, you have viruses like SARS-CoV-2 Guest: we all experience or all kinds of other viruses which are less dangerous for your own health. Guest: They infect our cells, human cells. But the majority of viruses in oral cavity Guest: actually are bacterial viruses we call bacteriophages. Guest: And that's the really like tip of the iceberg. We know very little what their Guest: role is in maintaining healthy oral cavity.

Guest: So the first studies are popping up and it's a really exciting area. Guest: So I'm looking forward to learn more about those. Siobhan: That's very interesting. When you were talking about SARS-CoV-2 and its effect, Siobhan: people will remember the reduction in taste and smell associated with that infection. Siobhan: Do we know anything about that in terms of the microbiome? Guest: Well, there are studies who've looked at the differences with people who got COVID and didn't.

Guest: I don't know exact outcomes, but I know that there were some differences, Guest: but those are small-scale studies. Guest: And regarding the taste, I think it's more neurological effects of the SARS Guest: virus and not so much via microbes. Guest: But nobody actually looked at it together, like neurological plus microbial effects. Guest: So maybe there is some synergy.

Siobhan: So going back to this idea, I'm sure it was the same when you were studying Siobhan: to be a dentist as when I was studying to be a doctor, this germ theory of disease, Siobhan: that all microbes are bad and that you have to get rid of them. Siobhan: And that's certainly something that seems very predominant in dentistry, Siobhan: this idea that you have to get rid of microbes and give broad spectrum antibiotics.

Siobhan: How can we change the information people are getting about that? What is the balance? Siobhan: Because that clearly there are potential pathogens that can infect the body. Siobhan: What's the sort of percentages? Are most of the microbes in the mouth either Siobhan: neutral or beneficial? Or what do we know about the diversity? Guest: Well, it's an excellent topic. And I think you're absolutely right.

Guest: I also remember the time when I was a student and we were really drilled that Guest: it has to be meticulously clean and microbes should be removed.

Guest: And definitely young moms shouldn't get these very aggressive Guest: bacteria which produce a lot of acids so Guest: that your kid doesn't get it and that's how Guest: so i tried to raise up my kids meticulously uh Guest: avoiding contact with them because i didn't want to spread my microbes and now Guest: we know that these microbes are essential also for kids for mom passing them Guest: to kids uh to to have them so uh yes how how do we um convince people that they

Guest: should take care of these microbes. Guest: I think we should spread the word about importance of microbial balance. Guest: And your question about what proportion is unbalanced or unhealthy for us. Guest: When we are healthy, they're all healthy. Guest: So also the ones which produce these smelly compounds, they are there because of their function.

Guest: They break down proteins and some other bacteria can use Guest: these amino acids for their own growth so Guest: if they're in low numbers they are commensals they are they just belong there Guest: yes because it should be as as as rich as as possible this community so it's Guest: like a rainforest you have different layers and they all need this ecosystem Guest: needs to be diverse to be sustainable. Guest: So that's why we don't call them pathogens when they are very low numbers.

Guest: And when they take overhand and increase and really start to rule the ecosystem, Guest: then, of course, we lose the balance. Guest: So that's what we call this biotic ecosystem. Guest: And then, indeed, it's too late already to talk about healthy microbiome. Guest: Yeah, so I don't see them as pathogens at all.

Siobhan: So there's this complex, sort of beautiful, diverse Amazonian rainforest that Siobhan: we have in our mouth that we need to look after because it's got huge benefits for us. Siobhan: So what do the microbes, these beneficial microbes, eat? You mentioned saliva. Siobhan: Is that where all their nutrients come from? Guest: So that's actually their main nutrient source and it's very rich and they grow happily on that.

Guest: And another source is this fluid seeping out through this crevice. Guest: So serum-like fluid coming from our blood through the gingival crevice, Guest: so the area next to the gum and the tooth. Guest: So there is this fluid which is rich with proteins. Guest: And these proteolytic or protein-loving bacteria really consume that. Guest: They prefer that to saliva.

Guest: And then, of course, we, due to our own diet, have trained our microbes to extract Guest: sugars very quickly from what we eat. Guest: So they can also consume sucrose if we eat a lot of sucrose-rich products, Guest: so they can use that for their energy, which is not for the good balance of Guest: your microbes, definitely not. Siobhan: So just going to the subject of saliva, which I've become fascinated with, Siobhan: you know, there's so many functions of saliva.

Siobhan: I wonder if you've mentioned a couple. Siobhan: One is providing nutrients for these beneficial microbes. And you also mentioned Siobhan: it contains antimicrobial peptides. Is that correct? Siobhan: Can you tell us some of the functions of saliva? Guest: Well, imagine not having saliva, waking up, dry mouth and the mouth doesn't wet.

Guest: So that day you will be experiencing a horrible day because you won't be able Guest: to talk, you won't be able to swallow, you won't be able to communicate and laugh. Guest: It's going to be painful. You start to get cracks in the sides of your lips. Guest: It's just a very, very unpleasant condition. And there are a lot of people having Guest: dry mouth. So from that, we learned that consequences of not having saliva at Guest: all are huge also to your oral health.

Guest: So what we see, these people get cavities very quickly because saliva also protects Guest: our teeth from losing mineral. Guest: Saliva is rich with calcium and phosphate. And those are minerals which needs Guest: to be balanced back into your tooth enamel so that you don't get a cavity. Guest: And with lack of saliva, we do see this happening very quickly. Guest: We see it with people who have medication, like most medications which are for

Guest: blood pressure reduction. They also have a side effect of inducing dry mouths. Guest: And then we see that these people have these poor health outcomes. Guest: The same happens to people who have radiation for head and neck cancers. Guest: They also have damaged cellulary glands, and we see these effects.

Guest: You get bad breath if you don't have saliva. Saliva keeps all these bacteria Guest: in low numbers, like you said, with antimicrobial substances, Guest: but also saliva has properties to, Guest: agglutinate meaning to co-aggregate bacteria with each other in bigger clumps Guest: and that helps swallowing them so we swallow these clumps of bacteria and it's Guest: not to see the gut it's just to pass it to the stomach and they will die in

Guest: stomach in this very acidic environment of stomach, Guest: so that's how saliva helps to to clear the stuff out of our mouth. Siobhan: So going on to another thing you mentioned what is a biofilm. Guest: Yeah, well, biofilms are everywhere. No microbes live flushing around somewhere Guest: freely, maybe in some extreme environments, temporarily in sea. Guest: But usually microbes prefer sitting on the surface somewhere and growing together.

Guest: So that's what makes them a biofilm, growing on a surface. Guest: And everything in our body, also on our skin, you don't see it, Guest: but there is a tiny biofilm of microbes. But you do see it in the mouse. Guest: So if you don't brush for a couple of days, you can see this white layer on your teeth. Guest: So that's definitely a biofilm. But we spoke about Anthony van Leeuwenhoek. Guest: He saw it and he removed it.

Guest: So that's the layer with bacteria, with fungi, with all the microbes embedded Guest: in slime. They make themselves. Guest: The slime protects them from being removed, from being dried out, Guest: protects them from antimicrobial agents. Guest: So that's why they are being killed easily if you remove this film and disperse Guest: but if you keep it on a tooth and try to kill, well, nothing much happens. Siobhan: So is it a sort of 3D structure, a net that the microorganisms attach to?

Guest: Well, it's actually even more complex. There are recently very beautiful images Guest: made from a group at Forsyth's Institute. Guest: They use a microscopy technique called classy fish And it's a 3D technique, Guest: confocal microscope, and you can see in different colors how different individual Guest: bacteria are structured. Guest: And what it shows, for instance, on a tongue, when you have these little papilla, Guest: like tiny thread structures of your own mucosal cells.

Guest: But they've shown that these bacteria form nice layers around these structures Guest: and they attach in really beautiful structures and suggesting that it has a function, Guest: that some bacteria need to sit together to help each other, to break down different nutrients, Guest: get from each other, so they communicate. Guest: That's also known that bacteria in biofilm communicate with each other. Guest: It's called quorum sensing. So they really talk. They're quite smart creatures.

Guest: And with these molecules, they influence also how they respond to the environment. Siobhan: So it's very similar to our social structures. We don't survive well living alone. Siobhan: We gather into villages and we cross-feed and help each other and chat to each Siobhan: other and then also chat to cities further away. Guest: Definitely. It's been coined quite some years ago that biofilms are cities of microbes.

Guest: It's really a city with the networks, with everything. So a complex city. Siobhan: It's fascinating. So biofilms can be a positive aspect. So what is plaque? Siobhan: Is that a type of biofilm or when does biofilm become plaque? Guest: Well, it is a biofilm, certainly. And it becomes a biofilm already from the Guest: first hours when you brush your teeth, Guest: then immediately already this protein-rich film based on saliva proteins will attach on your tooth.

Guest: And bacteria will have receptors again to attach on this protein film. Guest: And that will happen within a couple of hours. And the first ones attached there, Guest: they will start growing in about four hours, but new, new layers come there Guest: and they keep growing all simultaneously. Guest: So you will have a really visible film by the end of the day with your eye.

Guest: But of course, microscopically, it's there already at the beginning. so. Siobhan: What is when we're talking about the dental plaque which maybe some of the listeners Siobhan: will recognize you're going to your dentist and have it removed which is a kind Siobhan: of you know a white more solid substance um that's thought to be negative for your dental health.

Guest: Well that's because it's thick and mature plaque yes Guest: if uh we don't brush it Guest: very uh properly and there are places which Guest: is which are very difficult to reach by just brushing so Guest: it stays there and it can become hard then it Guest: becomes dental calculus and that one we cannot Guest: remove ourselves so then you have to go to dental professional Guest: or oral hygienist and that's being then professionally removed but basically

Guest: this soft substance dental plaque we should be able to remove ourselves if our Guest: mouth is healthy if we are unhealthy meaning that we have already these we call Guest: them pockets periodontal pockets. Guest: That's already the damaged tissue around the tooth and toothbrush doesn't go Guest: into this pocket so it's very difficult to clean that by yourself. Siobhan: And is that a space where these potential pathogens can aggregate and grow?

Guest: Oh, yeah, they love that. They love it. Because that fluid I was talking about, Guest: the serum-like fluid, it really flows like a sea there when you have inflammation, Guest: when these gums are inflamed and these bacteria having a party there indeed. Siobhan: Ah, so it's always a food source, a sort of free wine spilling from the gums, if you like. Siobhan: So you get these pathogens tracking Siobhan: down to those areas where there's high concentrations of these nutrients.

Siobhan: Okay, so what do we know we struggle with the gut microbiome in terms of what Siobhan: the healthy gut microbiome looks like? Is that the same with the oral microbiome? Siobhan: Do we know what a healthy oral microbiome looks like? Guest: No, that's a million dollar question. No, we still don't know and that's actually Guest: what I'm trying to research in all my research career.

Guest: I think we know so much about disease we know Guest: which microbes we don't want to have there but what Guest: makes the the remaining ones uh healthy we Guest: are just starting to scratch the surface it's it's Guest: the same like with the gut there is no one straight recipe Guest: what we've done we've addressed it in a cohort of young healthy volunteers uh Guest: they were meticulously checked their oral health their general health and it

Guest: appeared that we thought we could frame and make like this is how the healthy microbiome looks. Guest: But it appeared that there were several groups, like subdivisions. Guest: We clustered them in five different types of microbiomes. Guest: So I think it's not like one size fits all. Guest: Depending on your genome or your saliva properties, those determine also which Guest: microbes will like you and which won't.

Guest: That's why we see this heterogeneity. You can have a healthy microbiome, Guest: but very different from my microbiome.

Guest: So that makes it difficult for all these microbiome studies to say, Guest: what is then a healthy microbiome? Guest: So I think we shouldn't just be looking at what is there, but what are they Guest: doing, about which functions they're able to perform, and that these functions Guest: together make it a healthy balance with what you as a host need to have.

Siobhan: So if we go back to our city analogy, it would be the same that we couldn't Siobhan: say what a healthy, thriving city was just by listing the people who live there. Siobhan: It's more the activities and what they're producing and what they're manufacturing. Siobhan: And one city could be equally flourishing but have very different inhabitants. Would that be correct? Guest: Yeah, I love this allegory. I really like it.

Guest: So exactly. So just having a name doesn't mean anything. Like I mentioned, Guest: the streptococci, if you have the name, what's in the name? Guest: Because we know there are hundreds of different varieties of streptococci, Guest: and some are quite virulent, meaning can harm us. Guest: And some have so perfect beneficial capacities. They're protecting us from intruders. Guest: So you cannot just put them in one heap.

Siobhan: And it's also the idea you were saying of balance, that we can cope with a few Siobhan: potential pathogens if they're kept in check. Siobhan: They may even be beneficial in small numbers, but if they grow, Siobhan: get out of control and the balance, so you have more potential pathogens than Siobhan: beneficial microbes, is it correct to say that's when you have this problem Siobhan: if you're out of balance?

Guest: Yes, that's what we call dysbiosis. Also, that is still something we cannot define properly yet. Guest: So when is this tipping point? Guest: When do you enter dysbiosis? So we're also doing research currently on that. Guest: But for that, you need really long-term studies and to take a lot of samples Guest: in time and see how it changes in people who stay healthy or people who lose their health. Guest: So that takes a lot of effort.

Siobhan: So what are the most common oral diseases that people think about? Siobhan: And are they all caused by microbes? Guest: Let me think. Dental caries, you cannot say it's a microbial disease. Guest: We don't call it infectious disease because we don't think that there are specific microbes. Guest: And also, if you only have microbes and nothing else, you won't get cavities. Guest: You do need to have sugar.

Guest: So you do need to have this source of energy for bacteria to produce these acids. Guest: And these acids are the ones which make cavities. So, yes. Guest: So that would be definitely an oral disease where microbes are involved. Guest: Then you have another one, which is bad breath. We call it halitosis. Guest: I already mentioned that. Guest: We have these anaerobic bacteria which produce sulfur-containing compounds, Guest: and they're very, very smelly.

Guest: Think of like a rotten egg smell. So that kind of compounds. Guest: And yes, they make those in our oral cavity. Guest: And then one really, really...

Guest: Common disease and which has a lot of general health Guest: consequences is this periodontal disease and Guest: in old times it used to Guest: also be seen as a infectious disease that certain microbes Guest: do it and now we know better but it's actually the host so it's our body overreacting Guest: in a strange way to this microbial stimulus and it's also genetically determined Guest: so not everybody will have this disease but people who are susceptible,

Guest: they will respond to this biofilm and they will respond in a very different Guest: way than person who is not susceptible. Guest: And there are a lot of factors contributing. So besides this host response, Guest: besides microbes, it's also the lifestyle. Guest: So periodontal disease risk is much higher if you smoke, if you eat unhealthy. Guest: So all this piles up. And if you have a lot of stress.

Guest: So a lot of factors contribute to this disease. So we don't call it microbial disease. Guest: But yes, if you didn't have a biofilm, if you have, then again, Guest: this body didn't have anything to fight with. Guest: So yeah, then you didn't have the periodontal disease, I think. Siobhan: So when we talk about the gut, it's the largest surface area between us and Siobhan: the outside world and imminent pathogens and dangers.

Siobhan: And the mouth is the first portal, as you said. So it seems incredibly important Siobhan: that you have a good immune system there. Siobhan: In the gut, we talk about there being a one layer of cells between us and the outside world. Siobhan: I know we have mucus on top as well. So how does that work in the mouth? Siobhan: Is it the same? Is there one layer of cells?

Siobhan: And what protects us from these things that we're eating and inhaling all the Siobhan: time from getting into the body and causing havoc.

Guest: Well it's different than the Guest: gut because we don't have this uh one Guest: layer uh thing and and and Guest: also the mucus layer is different the cells are different like i said it's this Guest: desquamation so that's these cells really go quickly they leave the the top Guest: layer of this mucus uh and that mucus membrane so that way you clear the whatever Guest: was sitting there and torturing you. It's just gone.

Guest: Oral cavity, if you have a wound, it heals much faster than when you have a wound on your skin. Guest: And that's because of these properties of saliva. Guest: It has a lot of things which help wound healing. So that also protects us. Guest: Yeah, the swallowing, like I said, so you swallow it and then they are destroyed in the stomach acid. Guest: So all this systems work together. Yeah.

Guest: And most importantly, if you have your own microbes already sitting on all these Guest: places in your oral cavity, Guest: so whatever comes in and it's not Guest: human and it's not oral will be fought against. So it will be destroyed. Guest: There is a full warfare, both from microbes and from your immune system. Guest: So microbes sitting there will make sure the conditions are unfriendly for the ones coming in.

Siobhan: Okay, so it's like boots on the ground. So they're there taking up space and nutrients. And okay. Siobhan: So most listeners will be familiar with this idea of oral bacteria and dental Siobhan: decay, but many may be surprised about the connection between oral health and diseases further away. Siobhan: Can you give us an overview of the key research areas and evidence for systemic Siobhan: disease and the oral microbiome.

Guest: Well that's that's a really hot topic already Guest: for decades and uh it's also Guest: a difficult one there is certainly association Guest: the difficulty is in causality it's like the chicken and egg story like what Guest: was first poor oral health and and then influence on your systemic health or Guest: was it already something systemic and that's why you see the effects in oral Guest: cavity Are we really sure,

Guest: based on epidemiological studies, meaning that you look at large groups of patients Guest: and you see what diseases they have and which correlate, Guest: we do see a very strong correlation with this periodontal disease, Guest: so this destruction in your gums and also the dental bone, Guest: with diseases such as diabetes and then diabetes.

Guest: High blood pressure and other cardiovascular diseases. There is also relation Guest: with rheumatoid arthritis, relation with Alzheimer's disease, Guest: relation with pregnancy complications. Guest: So those are the studies where we know the numbers. Guest: You have more disease in oral cavity, you see more of these complications. Guest: The question is, like I said, what did what?

Guest: And those are difficult ones. But we do see, for instance, in pregnancy complications, Guest: that when there is premature birth or still birth or preeclampsia, Guest: we see that there are oral microbes found in placentas. Guest: And those are not the oral microbes which are health associated. Guest: Those are the ones coming from these deep pockets, coming from these areas with inflammation.

Guest: And the idea is that it happens through bloodstream because when you have inflammation Guest: in oral cavity, it's actually the whole body is responding to that. Guest: And with all these diseases I just mentioned, the common factor is chronic inflammation. Guest: And this inflammation in the gums, it's the same. Guest: It's chronic, it's invisible to the eye, it's below the gum line, Guest: but your body has to respond to it.

Guest: So we do measure, we see that people with this inflammation in the mouth has, Guest: for instance, high concentration of C-reactive protein in their blood, Guest: which is protein showing that somewhere there is inflammation. Guest: And when you treat the gum, this value goes down. So your body kind of relaxes. Guest: So what I think the link with these diseases is that they just have common mechanisms.

Guest: So that's why they co-occur. and if you treat one, it will also have a better Guest: effect on the other disease because this inflammation, of course, Guest: your body doesn't care where it is. Guest: It just fights it and that's what you then feel as a person.

Guest: There is evidence that, for instance, when you treat oral cavity and you are Guest: a diabetic patient with poor diabetic or glycemic control, Guest: studies show that when you treat periodontal disease, dysglycemic control parameters Guest: improve just by treating oral cavity. Guest: So definitely there is link from both sides. Guest: Either systemically you can treat or orally, these are definitely linked. Siobhan: So I understand, Professor, about the low-grade information.

Siobhan: So if you have potential pathogens triggering your immune system anywhere, Siobhan: then you will get a sort of systemic response all over. Siobhan: But that to me is slightly different from bacteria from the oral cavity entering Siobhan: the circulation and traveling to other places. Siobhan: Now, you mentioned one example, which is premature births, so traveling to the placenta.

Siobhan: And I know I read a paper, you have to correct me if I'm wrong, Siobhan: I think Malawi has one of the highest rates of preterm deliveries. Siobhan: And I think someone did some research where they try to improve oral hygiene Siobhan: of pregnant women there, and they actually reduce the number of premature deliveries. Siobhan: What's actually happening there? Are bacteria going to the placenta? Siobhan: Do we know what exactly is going on?

Guest: It's a huge debate about that. We also contributed in researching that.

Guest: There are a lot of papers showing that also in healthy pregnancies, Guest: bacteria are found in placenta. Guest: The question is, why are they going there and what are they doing there?

Guest: And most interestingly, the first paper on Guest: that was published by Kiersey Agard in Guest: 2014 already and I was here Guest: listening to her presentation at the conference and Guest: then I came back and I was like talking to my colleagues because the Guest: most amazing thing she presented was that she found that Guest: in these healthy pregnancies placenta contained microbiome Guest: which resembled that of the tongue and tonsils Guest: and not any of the organs in a

Guest: near neighborhood of placenta and so then Guest: we were puzzling and sitting like why would oral Guest: bacteria go there at a healthy state what would Guest: be the physiological role of that and we wrote a hypothesis paper which shown Guest: that some studies later on showed that yes indeed there this might be true on Guest: animal studies at least showing and a hypothesis was that you know most women when they are pregnant, Guest: experience something called pregnancy gingivitis,

Guest: that your gums are swollen. Guest: Even if you are doing your best and brushing your teeth, you still have swollen Guest: gums. And why are they swollen? Guest: It's because in our gums, there are receptors for the hormones, Guest: for the sexual hormones. Guest: And these hormones are, of course, having an enormous peak during pregnancy.

Guest: And due to these hormonal effects, so this swelling of your gums allows actually Guest: microbes from this crevice next to the tooth and the gum allows these microbes Guest: to get into the bloodstream. Guest: Because what is swelling? Swelling is opening the blood vessel and getting wider. Guest: So we think it's a natural physiological way for these oral bacteria to be allowed

Guest: to pick up. and they go to the organ which is developing most at that time, Guest: which is placenta, growing very hard. Guest: And they are trapped there. They're not there to inoculate or infect the child. Guest: They're trapped there. They're probably not living. Guest: They might be only bacterial fragments. And what we think, they are there for Guest: fetal immune system already to sniffle around and to acquire genetic information Guest: about these microbes of mom.

Guest: So, okay, my mom had these. So this is probably good for me, too, Guest: so that your acquiring microbes in your first day happens in a safe way, Guest: that your newly established immune system already recognizes what is good and what's not good for you. Guest: That's a theory, and we're waiting for exciting experiments to show that is it this way or not.

Guest: But that would explain why these oral bacteria are allowed to travel all the Guest: way there and why do we get these swollen gums. Guest: On a side note, this also would mean that it's extremely important to have really, Guest: really good oral health when you are expecting mom, because you want your kids, Guest: your fetus, to experience good microbes and not the ones which are going to be harmful later.

Guest: So that's why also these complications, pregnancy complications, Guest: like I said, having these bad bugs going all the way to placenta, Guest: you don't want those there. Siobhan: You also mentioned dementia and I know that you co-authored a review about the

Siobhan: oral microbiome and Alzheimer's disease, I think. Siobhan: What's happening in this area? Are we again talking about specific bacteria Siobhan: and are they crossing the blood-brain barrier and what's happening there? Siobhan: I mean, it sounds fascinating. I know they've actually found specific bacteria Siobhan: in cerebral spinal fluid, so in brain tissue. Tell us more about this.

Guest: Well, it's another exciting topic of research, but like I said, Guest: again, the causality, it's very vague. Guest: The studies which you mentioned, they actually find oral bacteria in fluid in Guest: brains and in cerebral fluid of people who have deceased from Alzheimer's disease. Guest: So these people didn't have healthy barrier or anything.

Guest: They They already had most things were deteriorating. So when you find strange Guest: things in the brain of very, very ill people after their deaths, Guest: the question is, were the things there because already nothing was functioning properly? Guest: Or were they there at the first place and did they cause the disease?

Guest: We don't know that. So there's a lot of research going on, a lot of animal research Guest: showing, yes, that oral bacteria can produce structures which resemble these Guest: blocks in Alzheimer's patient brain. Guest: But is this really happening that way also in the human brain and in the time Guest: of the disease course? Because it takes years. Guest: And when you find these organisms there at the end stage, is the question.

Guest: What were they doing there all the time they cannot grow there Guest: they're in very low numbers so it's not Guest: very convincing that their role is in initiating Guest: disease but yes there is again Guest: association with dementia and poor Guest: oral health and there are explanations for Guest: instance if you lack your teeth because of the Guest: poor oral health and your teeth has been extracted you cannot Guest: chew properly so you tend to eat more soft

Guest: foods and there's research done that if you Guest: don't chew you don't train the muscles Guest: the chewing muscles are really very Guest: lazy and not chewing will make Guest: you cognitively go a little bit backwards Guest: we see it in elderly if they are in elderly homes Guest: eat only the soft foods the cognitive health Guest: declines compared to ones who are chewing healthy foods so it's it's all connected

Guest: so this this general thing that that oral cavity needs to function properly Guest: affects your well-being including your mental health that's. Siobhan: Fascinating because there's a lot about resistance training and cognitive health Siobhan: and how important it is but i have never thought about the masseter muscles Siobhan: which are your jaw muscles as being part of resistance training if you like that it's it's you know.

Guest: A muscle workout it is and people forget about it people think oh i can only Guest: sit in a wheelchair i can do anything no you can chew wow. Siobhan: That's yeah that's very interesting so um Siobhan: just going back to the dementia aspects so they have found i think it was p Siobhan: gingivalis it crosses the blood-brain barrier and was found in these fluids Siobhan: or in brain tissue um they mentioned something called gingipanes what are those and what do they mean.

Guest: Yeah those are uh proteases those are Guest: enzymes which can cleave proteins so these Guest: these uh proteases help this bacterium to survive in strange environments and Guest: that's why it can go into cells so uh this how does it do it by passing the Guest: blood brain barrier we don't have evidence that it's able to do it. Guest: Like I said, we do find these bacteria, but then the blood-brain barrier was Guest: not functioning well anymore.

Guest: But these ginger pains have special talents, yes.

Siobhan: Would you get bacteria in healthy brains, as far as we know? Guest: No, we don't have evidence for that. Siobhan: So just moving on, because I have a list. People were so fascinated by this Siobhan: topic, Professor Zahra, and I have a list as long as you are more questions. Siobhan: I'm just going to pick a few. Siobhan: If we just start with one that was very popular about biotics, Siobhan: so prebiotics and probiotics for oral microbiome health.

Siobhan: I wonder if you could just outline what those terms mean and what the evidence is for using them. Guest: Well, probiotics are bacteria beneficial for our health. Guest: So for whatever health, it could be gut health, mental health, oral health. Guest: And prebiotics are substances which allow these beneficial bacteria to grow happily. Guest: So for oral cavity, we can use both pre- and probiotics. Guest: There's less research done compared to the gut pre- and probiotic research.

Guest: Most probiotics, so bacteria for good health, actually are gut bacteria, Guest: meaning that, well, we are using the bacteria in oral cavity, Guest: which maybe do the best job in the gut, but not in oral cavity. Guest: So there's still plenty of work to do to develop better probiotics specifically Guest: designed for oral health. Guest: But there are advanced studies already. Siobhan: Toothpaste, for example, there's a huge range of prices with toothpaste.

Siobhan: Would it be correct to say i mean some people use just salt water i mean i know Siobhan: there's controversies about fluoride Siobhan: at the moment what are your views on toothpaste choice and the oral. Guest: Microbiome if. Siobhan: There are any views.

Guest: Yeah the the great advantage of of Guest: toothpaste is that we can add substances there which Guest: we think which definitely help which work in the Guest: westernized society where we eat unhealthy where Guest: we eat a lot of sugars so that's why we do put Guest: fluoride in toothpaste because fluoride is shown really to Guest: help preventing these cavities if Guest: you eat healthy you don't need fluoride but hardly anyone Guest: manages to survive without any snacks so yes

Guest: you can keep brushing just with salt solution just with plain water as long Guest: as you brush because mechanical removal of this biofilm helps already but you Guest: cannot get with your brush everywhere so the The reason that we use toothpaste Guest: is that it has substances which can stay there and do their work after you've brushed. Guest: So it will stick to the remaining biofilm and still do the work.

Siobhan: What about mouthwashes? There's been a lot of negative views on mouthwashes Siobhan: and the oral microbiome. Could you explain those to us? Guest: Again, it depends what's in the mousewash. What's the aim of a manufacturer Guest: for that particular mousewash?

Guest: If you see mousewashes which are there with fluoride, like supporting teenagers Guest: who have orthodontic braces and they have difficulties with getting this toothbrush Guest: everywhere to remove this biofilm, Guest: then rinsing with fluoride-containing mousewash helps to prevent these white Guest: spots or lesions next to the braces. Guest: So that's perfectly safe. Guest: Then you have mousewashes, which are claimed that they kill 99% of all bacteria.

Guest: I would really not advise using those if you have no issues with your oral cavity. Guest: If your dental professional suggests that you should use a mousewash, Guest: then discuss which one is most suitable for you. Guest: Because just choosing something very aggressive means that 99% killing means Guest: all your good bugs will be killed first because they are there in superficial layers.

Guest: So you will kill those. And these deep crypts, deep pockets with these less Guest: beneficial bacteria will still stay there because mousewash doesn't get there. Siobhan: So I was particularly interested in this idea of nitrates and oral health and systemic health.

Siobhan: So there are these bacteria you may have to explain to me that if you use mouthwashes Siobhan: and you're removing them, Siobhan: these bacteria that can transfer nitrates in food to nitrites, Siobhan: can you explain to the listeners what that's about and how it could affect your blood pressure? Guest: Well, it's a really elegant story how our co-evolution with microbes made it Guest: happen that we have benefit from these microbes.

Guest: So what we eat, if we eat healthy, a lot of foods like green leafy vegetables, Guest: red beets, they contain a lot of nitrate. Guest: And nitrate is a molecule which in our body should be reduced to nitrite. Guest: And from nitrite, nitric oxide is being made. And this nitric oxide has a lot Guest: of physiological roles.

Guest: One of them you mentioned, regulating blood pressure. So in presence of nitric Guest: oxide, your blood vessels relax, and that leads to reduction of your blood pressure. Guest: But it has many other functions, so it's really a nice physiologically beneficial molecule. Guest: The problem with our body is that we lack enzymes which do the first step from Guest: this dietary nitrate to, Guest: It needs to be reduced into nitrite. We cannot do it. We are handicapped.

Guest: But these microbes in our oral cavity can. Guest: And why oral cavity and why not the gut? Because the next step happens into the stomach. Guest: So the reduction of nitrite into nitric oxide happens in this low pH conditions of your stomach. Guest: That's why gut bacteria don't have a chance to do anything about it. Guest: It has to happen in the mouth.

Guest: But then, again, you would wonder, do I have to sit with this red beet or spinach Guest: in my mouth for half an hour and chew and chew and chew so that these bacteria can reduce it? Guest: No, even that is not necessary. You can just swallow. And what happens, Guest: we call it entero salivary pathway. Guest: So you swallow the food. It goes into the gut. And then into the intestines, Guest: this nitrate is being absorbed into your blood. Guest: Blood brings it to your salivary glands.

Guest: And then it is actually concentrated back into saliva. Guest: You get your nitrate in saliva coming through your guts, through your blood, back to mouth. Guest: And then when you're doing something completely else, your oral microbes can Guest: peacefully just reduce the nitrate into nitrite. Siobhan: This is astonishing. So you're saying when I'm swallowing my beetroot soup, Siobhan: which is high in nitrates, I swallow it into my stomach.

Siobhan: It goes into my intestine, gets reabsorbed in the circulation and goes back Siobhan: to the salivary glands, is re-secreted into the mouth and the oral microbes Siobhan: chemically modify it further. Guest: Yes, and that's how you produce this nitric oxide, which you need in your body. Siobhan: So this nitric oxide increase has health benefits such as it reduces my blood Siobhan: pressure, will reduce my platelet stickiness, it will improve my blood vessel wall flexibility.

Siobhan: So all these brilliant things in my cardiovascular system, all that can come Siobhan: from beetroot and the oral microbes. I mean, that's incredible. Guest: Yes, even more important that not just beetroot, you can keep eating a lot of Guest: healthy things, but if your mouse doesn't contain these microbes who can do Guest: that, so exceptionally these healthy ones can do it.

Guest: And there are studies showing that they had a test group rinsing oral cavity Guest: with chlorhexidine, which is broad spectrum antimicrobial, and the control group. Guest: And then this test group actually could not reduce this nitrate anymore, Guest: and they didn't have the beneficial effect on blood pressure. Siobhan: Right. So rinsing with a broad-spectrum mouthwash could increase my blood pressure. Guest: Indirectly, yes.

Siobhan: Indirectly, yes. Absolutely amazing. So carrying on with the food and drink Siobhan: theme, beverages, so tea and coffee and their effect on the oral microbiome, Siobhan: what do we know about that? Guest: Well, there are studies looking at the different substances. Guest: We know that tea, for instance, has a lot of these polyphenols and a lot of Guest: antimicrobial substances, also fluorides in green tea. Guest: So a lot of chemical active compounds.

Guest: So we call them functional foods. The same goes for cranberries, Guest: which have been shown to have antibacterial activity. Guest: Also shiitake mushrooms, all kinds of stuff. We've also done research on extracting Guest: these substances and testing. Guest: So, yes, there are products containing these plant or food-based compounds used Guest: already in some oral care products.

Guest: So I think there are still a lot of possibilities because they're definitely Guest: friendlier to your microbiome than these aggressive antimicrobials. Siobhan: So what about smoking and vapes and the oral microbiome? Guest: Oh, there we go. Now, don't do that. Don't smoke and don't replace smoking with Guest: vaping because the effects will be the same. Guest: It really damages your microbiome. There's really elegant study done by a group Guest: of Purnima Kumar in Ohio State University.

Guest: And what they did, they looked at people without any oral diseases, Guest: but they compared smokers, former smokers and current smokers. Guest: And they actually looked at their microbes below the gum line. Guest: So in this crevice. And what they found that the smokers had microbiome, Guest: which was really already dysbiotic. Guest: It looked like as if they already had this periodontal disease.

Guest: Well, there was no disease, but microbes already were very, very towards that state. So don't do it. Guest: That's what I already mentioned, that for periodontal disease, Guest: one of the risk factors is smoking. Siobhan: Yeah. What about alcohol? Guest: Yeah, alcohol. Alcohol, I think... Guest: Lots of alcohol is not good for anything and also not for your oral cavity because

Guest: some bacteria can metabolize some molecules from alcohol. I think it's acetaldehyde Guest: and that can be cancerogenic. Guest: So you don't want to have those molecules swimming around in your body and that Guest: oral bacteria happen to be able to make those. Siobhan: And when we talk about toxins, we don't usually think of medications as toxins.

Siobhan: But when we talk about human microbiomes, it often is the case that various Siobhan: commonly taken medications can be very disruptive to our human microbiomes. Siobhan: Is that the case for the oral microbiomes? Guest: There's not very much research done. There's research on antibiotics. Guest: So we know that, well, our own group, we did study a large EU project that antibiotics, Guest: we were looking at effects in oral cavity and in the gut, the same individuals.

Guest: They were healthy and they were followed for one year after antibiotic exposure. Guest: And we saw that the gut really showed severe destruction of the microbiome, Guest: while in oral cavity it stayed stable. Guest: But those were healthy individuals. If you would have a disease and you would Guest: have repeated antibiotic courses, then we definitely would see that oral cavity also will collapse.

Guest: And we do see that there is a loss of diversity and the beneficial bacteria Guest: are gone and these opportunistic pathogens can take overhand. Guest: Yes, there are effects which are certainly not beneficial. Siobhan: So we have one interesting question about intimate relationships. Siobhan: So kissing and oral sex and its effect on the oral microbiome, Siobhan: has that been researched? Do we know anything about that? Guest: Oh, this is a very interesting question.

Guest: I was searching on this and I know that there is one study done in Amsterdam Guest: when they opened the world's only microbe museum. It's called Micropia. Guest: And by opening this museum, they asked couples entering the park, are they a couple? Guest: And if so, are they kissing intimately? Guest: And yes, when they say yes, they asked them if they want to participate in the study.

Guest: So what they did, they took a sample from the oral cavity before they kissed from the both partners. Guest: And then they asked them to do the French kiss, the very intimate kiss. Guest: And then they took another sample. and then they also asked one of the partners Guest: to rinse with probiotic-containing drink and then again kiss the partner. Guest: So then they compared all these different samples. Guest: The conclusion was, well, if you are a couple, you don't really share a lot

Guest: of microbes. Not in that small study. They couldn't find it. Guest: And once you have your mouth full of these probiotic microbes and five minutes Guest: later you kiss somebody, You transfer part of them, but this part was very, Guest: very small and disappeared very quickly. Guest: So again, it shows that what's in your mouth is protecting you from all the Guest: things coming by, passing by. Guest: It will change if something happens to your general health.

Guest: If your immune system is malfunctioning, if you are having some immune system Guest: suppressive therapy, it will be different. Guest: So definitely, if you're healthy and nothing is strange, then you're perfectly Guest: safe kissing whoever you want. Guest: But of course, do it safely. All other forms of sex, I couldn't find any studies Guest: on that, how it affects oral cavity. Guest: But I did find that oral microbes have been found in vaginal flora of women who have vaginosis.

Guest: So again, that it disturbs microbes at different sites in the body. Guest: So yeah, it can have both ways some effect. Siobhan: Now, finally, there was just one question here on the impact of cosmetic procedures. Siobhan: So, it's braces, dentures, fillings. Siobhan: Do we know anything about the effect of those on the oral microbiome? Guest: Well, there's also a lot of research ongoing, especially these clear liners, Guest: like this new kind of braces, which you just carry.

Guest: So, I'm very curious what that does to the ecosystem. But the braces, Guest: we know, actually do not so much, except that they allow accumulation of biofilm Guest: much more than without braces. Guest: That's what I already mentioned earlier, that these people have difficulties Guest: keeping everything meticulously clean. And there are these block retention sites Guest: due to the physical brace itself.

Guest: And that's why this biofilm can remain there unnoticed and can't start damaging your tooth enamel. Guest: So then you have to really need some help. some professional needs to help you Guest: clean it so that's the only thing and when you remove braces we see that microburn Guest: returns back to to what it was because you can clean again everything very easily Guest: and normally when the teeth are in correct shape it even gets better than before you had braces oh.

Siobhan: Professor zara thank you so much for sharing your incredible knowledge uh with Siobhan: us today it's really clear and it should be to the listeners that this community Siobhan: of beneficial microbes that live and work in our mouths are vital to so many Siobhan: aspects of our general health. Siobhan: And your work has made such a significant contribution to this fascinating area of medicine.

Siobhan: I shall be watching what you do next with great interest. So thank you so much Siobhan: for coming to talk to us today. Guest: Well, thank you for picking up this topic, finally. And thank you for having me. Siobhan: Thanks to the listeners for tuning into this episode of Microbiomedics. Siobhan: Stay curious, keep flossing and we'll see you next time. Intro and Outro: Thank you so much for listening to this episode of Microbiomedics Podcast.

Intro and Outro: We really hope you enjoy the content and we welcome your feedback. Intro and Outro: We'd love to hear any suggestions you might have for microbiome topics that Intro and Outro: you'd like us to cover and we also appreciate listeners' questions and we'll Intro and Outro: endeavour to answer them in the next podcast.