Is Killing Bacteria the Wrong Way? The Future of Oral Microbiome Modulation

In this episode of Let's Talk Oral Health, hosts Martijn Verhulst and Rachel Chau sit down with Professor Wim Teughels, a leading researcher in oral microbiology from KU Leuven. Together, they explore a major shift in dentistry: moving away from the broad elimination of bacteria toward the "stewardship" of a healthy, resilient human oral microbiome.

Transcript

Welcome And Guest Introduction

Rachel Chau, DDS 0:19

Welcome to Let's Talk Oral Health by GUM, your thoughtful conversations on Oral Health and Beyond. My name is Rachel Chau, and I'm here with my co-host, Martijn Verhulst. Hi Martijn. Hello. How are you?

Martijn Verhulst, PhD 0:30

I'm very well.

Rachel Chau, DDS 0:31

For today's episode, we are very honored to welcome an expert on All Microbiome. And with him, we are going to dive into the fascinating world of microbes and their interactions between themselves but also with the mouth. I'm talking about Professor Wim Teughels. Hello, Wim.

Prof. Wim Teughels 0:49

Hi, Rachel and Martijn. Thank you for having me here.

Rachel Chau, DDS 0:53

Thank you for accepting our invitation to come to Sunstar headquarters in Switzerland. We are very happy to have you with us.

Prof. Wim Teughels 1:00

It's my pleasure.

Rachel Chau, DDS 1:01

We are very eager to uh start the conversation on our microbiome with you. But before we do that, uh let's start by introducing you a little bit to our audience. So you are a professor of periodontology at the University of Leuven in Belgium. Can you maybe tell us a bit more about your career, your

A Dentist Who Fell For Microbes

Rachel Chau, DDS 1:20

uh research area, and uh what you do over there?

Prof. Wim Teughels 1:23

From an educational point of view, I'm I'm a clinician, I'm a dentist who actually got uh interested in oral microbiology during his uh dental training. And and it's a little bit of a strange story, but I actually got interested uh in oral microbiology by being lazy. And the story behind that is that in my I think third or my fourth year of dental school, I need to write up a thesis like everybody, a master thesis. And I didn't really feel like writing too much and doing an extensive uh uh literature research. But I had a friend who was doing a PhD in oral microbiology, so I thought if I do something in that field, he will give me some data and I can write an easy, easy master thesis. So I applied to the period department to connect up and to work together with my friends, and I was accepted, but they connected me to another PhD student who uh basically pushed me to work day and night in microbial culturing, one plate after the other, and I fell in love with these bacteria, so I ended up in in oral microbiology. So the rest is history doing the normal postgraduate uh oral microbiology uh PhD. Um during my PhD, I came into connection with Mike Newman from uh UCLA and basically was now the head of the Carensus uh textbook. Uh we connected well, we started to to chat about microbial interactions. This led to the probiotics field, and and my career started up. So now I'm focusing primarily, not only, but primarily on microbial modulation uh and and modulation of the oral ecology. And you you do research in this field of microbiology, but you also still treat patients, if I'm not mistaken, right? I'm I'm still uh very I think almost 40% of my time is still patient treatment. And I really see this as an advantage. Um, in the old days I I felt always bad because you have this really big basic scientist that really can go dive into the molecular microbiology, which I couldn't understand, but I was also not a real clinician. Now, so many years later, I really see it as an advantage because I can talk to the both sides and I can easily bring experiments of things that we notice in in the lab to my patients really fast, but also treatments or or changes or experiences of my patients. I can really easily bring them back to my lab and see what is the reason behind that and how we can use this. I really feel myself more as a translational research, bridging the the two fields, and I'm very happy with that. I I would not want to have anything else. So it's not a very common combination, as you said. Usually the very either very fundamental basic researchers, or you have the the very much clinic clinic clinical practice focused uh type of uh that is the the fun part because I can actually use that outside of the um of the oral oral microbiology field. So I'm also involved in in some environmental probiotic, pre-biotic uh modulation projects. And also there, my my contribution to the project is often the translation of things to to real life settings and and back. So that's that's a thing I love to do now.

Rachel Chau, DDS 5:08

But we are definitely going to uh tackle into these two expertise of yours during our conversations because we are always trying to indeed bring science, in for scientific information to our audience, but try to also have an application, a pragmatic uh application to uh to that, since our audience uh uh is mainly overcome professionals. So maybe let's start to dive now directly

The Shift From Pathogens To Ecology

Rachel Chau, DDS 5:30

into the topic. And I would like to uh start with the uh the shift that we have encountered in the past years from the concept of period pathogens or chyrogenic bacteria towards a balance of the ecosystem. Can you maybe set the stage for us and explain uh this paradigm shift that happened?

Prof. Wim Teughels 5:52

So when I I still was a student, um what we often did was we looked for specific pathogens. We knew, okay, periodontal disease is related to these and these and these pathogens. For 2 decay, we have the typical strep newtons, uh, strepsobrinous. Um and and we were focusing on eliminating these pathogens. So often when when I still was a student, we were taking microbiological samples to see what was there. At the end of therapy, we were checking whether or not they were still there or not. And often it was a disappointment because they were still there. Now, over the years, logically, we see this shift and a change in our understanding that actually almost every human being is being colonized by these pathogens. They are everywhere, but we start to understand that there is this whole bunch of bacteria that we were not interested in in the 2000s up to 2010 that actually play a crucial role in oral health. So the importance of something which we call commensal slash maybe beneficial bacteria became way more clear. And then uh pioneers like like Philip March uh came up with the concept that look, it is not these pathogens that are of importance, but it's the whole microbial community. It's not only about their numbers, but it also how they interact with each other, how they interact with the immune system, how their metabolic activities, which virulence factors that they produce. And this is all regulated very tightly between these groups of bacteria. This made that by by 2015, something like that, we actually left the concept of looking at specific pathogens. We we know that the old pathogens that we know basically from from the 60s, the 70s, that they are in a way a little bit of a marker organisms for how what we call now dysbiotic your biofilm is, or how bad your biofilm is, or good our biofilm is, but it's not a treatment target anymore. They can give you an idea, an indication, but it's it's not a treatment target. So um sorry to interrupt that, but what at that point in 2015, what triggered that that change of perspective? Because the there has always been this belief, at least for a few decades, that these were the pathogens that you need to eliminate. So, what exactly was the new insight at that time that that you know? I think it it it was um two things. On on one hand, it was the the Philip March ecological um plaque hypothesis that that came up around that time, where you really had uh both for for 2TK and for periodontal disease, the shifts. Um, that was one thing. Then we had also the the Keystone uh theory, which came up from uh George Hagen, sorry for the name, Hagen Dali. And and in a way they they match to each other. There's also the period where we we started to have insights with the whole genome sequencing. So we started to realize that there is way more than just these 1015 bacteria where we have been been uh focusing on, and that even in healthy situations they they were still there. So we couldn't find one or two or three typical pathogens, what you would normally find in an infectious disease. But we saw that things changed when when you went from health to disease and and and back, and this was basically the basis of the whole concept that maybe we should go away from the classical approach of killing all the bacteria in their own cavity to shifting them because probably it's impossible to kill them. And then a second um angle came with the recognition, the understanding that these beneficial, I will call them beneficial bacteria, that they actually play an a very important role in keeping these these balances um straight, yeah, so that they were suppressing the outcome of patches, but that these beneficial bacteria were also very important in uh modulating the host response, modulating inflammatory responses. And this leads actually to the current concept of microbial balances and um trying to create stable ecologies rather than eliminating bacteria.

Rachel Chau, DDS 10:56

But then when you talk about balance, you are then uh mentioning

Eubiosis Dysbiosis And Resilience

Rachel Chau, DDS 11:00

eubiosis, to which we have to oppose, you already mentioned it, dysbiosis. So can you detail a bit these two uh two notions and what happens when dysbiosis strikes?

Prof. Wim Teughels 11:13

Eubiosis and dysbiosis are are two terms that you will hear more and more also in the future. So when we are talking about ubiosis, then we are talking about uh a biofilm microbial ecology which is in balance with health. So most often this relates to high numbers of beneficial bacteria, lower numbers of so-called pathobions, pathogenic bacteria, and something which induces uh a low inflammatory response. This is eubiosis, something which relates to oral health, periodontal health. When we talk about dysbiosis, then we're talking about the situation where you have an outgrowth of certain groups of bacteria, most of the time, bacteria that are um recognized to having a lot of virulence factors that are able to trigger the inflammatory response. So this biosis is often also connected towards an increased inflammatory response, increased bleeding on probing, um, increased furulence. So these are the two extremes. Now, what happens is due to environmental changes, uh an ecology can go from an uh eubiotic state to a dysbiotic state. Now, one concept is is still important there that is resilience. So eubiosis is although it's it's a healthy uh situation, it's actually a very stable situation. This this ecology really can withstand a lot of pressures from outside and still remain in a ubiotic situation. Now, when you went from ubiosis to dysbiosis to a pathogenic state, unfortunately this uh stability, this resilience uh also establishes. So also the dysbiotic state can be a very stable situation. And this is actually hampering treatment because if treatment is not uh really focused well, uh immediately, although you can induce a little bit of the shift in this biosis toward eubiasis, the resilience will bring it back to a dysbiotic change. And this makes that maybe in the future we have to work in in on these biofilms in other ways in order to bypass this resilience, to bring it in a different state, probably a eubiotic state, but again with sufficient amount of resilience. Going back to this eubious, dysbiosis, trying to think about it from a I almost say like a temporal way, and the way how it associates with health and disease? Of course, I can imagine dysbiosis is associated with disease, periodal disease, uh carriers, whereas ubiosis is considered with a stable healthy situation. Does um a dysbiosis always precede a disease? Or it's a bit of a tricky question, like a chicken and the chicken and the egg. You know, what comes first? Um, how do those two situations, so dysbiosis to disease state, how do they relate on a in a temporal basis? Based on on the most recent data, you can look at it from different perspectives. So, for instance, for dysbiosis, I could say, well, Martin, what's first there? Are the the pathogenic component of your biofilm growing out first? And is that then reducing the beneficial component, or is the pathogenic component growing out because you're losing the beneficial component? On the other hand, you could say with inflammation, do you first get inflammation which improves the dysbiosis, or do you get first dysbiosis and then you get inflammation? Probably it's something that runs a little bit in parallel, right? But based on on very recent data that I saw, some molecular biologists seem to tend that you can already see dysbiotic states before there are clinical signs of disease. It might be that that the dysbiosis trigger to something precedes, at least it precedes the clinical science. Yeah. That is very sure. If it precedes inflammation, I'm not sure. I think it's really a a coordinated, balanced interpretation. Yeah, yeah. We always refer to this like this vicious cycle. Um but then even in the cycle of work, of course, it's a question where where does it start and how do you break that cycle? Yeah, and and that's that's always, I mean, as you said, it's a tricky question, but it's an interesting concept, I think. Yeah, it is.

Rachel Chau, DDS 16:03

But I would like to come uh

Inflammation And The Hidden Systemic Link

Rachel Chau, DDS 16:05

back to something you said about working on resilience, basically to make it work in our favor. What are the factors that could affect the resilience and that we could work on?

Prof. Wim Teughels 16:16

Resilience is is um one of these newer concepts. So the factors are are still a bit always with a question mark. Uh, but what for sure is in favor of resilience is is a good oral hygiene. Basically meaning uh a good plaque control, a good biofilm control. Don't let it come too much. Although I admit that I have for sure seen patients that have a huge amount of plaque, have actually hardly any biofilm control, and are extremely resilient towards periodontal disease and 2 decay. They exist. This is the minority of the people. On the other hand, it has a lot to do also with with inflammation. I think if if you can keep a low grade of inflammation, low grades of inflammation will actually be will help in resilience. Or the other way around, if there is a lot of inflammation, the chance that you stay in a in a resilient uh eurosis state is is very low. You mean a local local inflammation or a systemic inflammation or both? Actually both for me. Uh I I in my perspective, based on what I've I've read and seen in the literature and in studies we did, I think that we don't have to underestimate the systemic inflammatory pathway. I think this is extremely underestimated. The local is very easy that we understand. I mean, you have a uh gingival sulcus, a periodontal pocket, there is bleeding, there is a lot of serum, so there is protein. These groups of of pathogenic uh bacteria are often proteolytic, so they can use it, and these proteins can inhibit, for instance, the peroxides that are in the biofoam that keep the pathogens under control. It becomes a a different story with systemic inflammation because it is not that extreme. You you don't really you often don't see it, but it's a low grade of inflammation that is uh actually triggering uh the immune cells to be hyper-responsive. So you get a different type of microphagus, for instance, just because there is systemic inflammation, it's something you don't see immediately clinically, you don't see extreme redness or whatever, but it makes the patients more susceptible to going into a dysbios state. Yeah, yeah. So your inflammatory response is more uh exaggerated than it would have to be today. So that that's why I I I really think that um we have been talking for a long time about the oral health systemic health condition, yeah, yeah, which is something which is really well established, where we have really evidence that it is there, how it works, for which diseases it's important. But now you feel that within the at least at the moment in the scientific community, we are more thinking in the other way. I would call it the gut microbiome or microbiome connection, where we are wondering to which extent the gut microbiome and the systemic inflammation that it is causing. We all know this from all sorts of um irritable bowel syndrome, Crohn's disease, how how important this is. Yeah. So we are now wondering how much the maybe this biosis or eubiosis in the gut microbiome, which also exists there, is actually influencing the the oral microbiome. And I'm honestly personally I'm I'm a big believer that it is a very underestimated pathway what we that we are looking at. And it might be very surprising how strongly the gut microbiome is actually influencing the oral microbiome without knowing communication line in the gum gut axis, I mean if if you think about how we have data these days, how the gut microbiome can influence, for instance, depression. So there is a gut brain access, very clearly shown, very nice research, both in animal research, in clinical trials. I mean, if the gut microbiome can do that, then it for sure should have something on especially because they're they're part of the same tract. Yeah, part of the tract. And and you have a constant inflow. I mean raw bacteria coming into the gut might be a little bit more difficult for the gut bacteria to come into the cavity, but in theory, with with the new translocation mechanisms that I see being understood now in in science, how these bacteria can travel from one remote site in the human body to the other remote site, then I would not be surprised that it would also go go into the other direction. Yeah, yeah. Maybe it's not even the translocation itself, but it's through other mediators that we maybe don't do not even measure yet. No. Um for sure. But but for sure, the the inflammatory pathways and and the immune modulation is is is a very important one. Uh um it's not all about the bacteria, it's the combination between the host and the bacteria, and the immune system is there, they're a very important aspect of.

Rachel Chau, DDS 21:56

You mentioned one of the factors, just to come back to the resilience. um to how to module act on it. You mentioned the oral biofilm, basically the how to uh take care control the oral hygiene

Biofilm Networks And Why Disruption Matters

Rachel Chau, DDS 22:10

that allows them to uh work on the oral biofilm. Can you maybe talk a bit more on maybe um when you have an accumulation of uh of a biofilm you have communication probably between the bacteria like some some uh some sort of influence on the roles of each other so how can you maybe detail that to us to understand really the role of the biofilm in resilience?

Prof. Wim Teughels 22:34

The biofilm allows a very close communication between between different sorts of bacteria and it it's it's very well known that um a biofilm is just not uh a a bunch of bacteria that are by coincidence text to each other so they actually build intensive networks collaborative networks where they use each other's uh metabolic pathways now this means that the whole biofilm process is very uh biofilm buildup process is very specific but this also means that if you disturb this process you actually can slow down the transition of of of biofilms uh towards going into a diseased state because each time these biofilms or or the bacteria in these biofilms need to re-establish these metabolic networks and that takes time the fun part there is because we start to realize that there are these metabolic networks is all also points of engagement. I mean if if we know which metabolic networks are working we could interfere with this metabolic network both in a positive or in a negative way in order to try to strengthen the the the resilience and prevent basically because what is strengthening resilience is preventing the outgrowth of of of certain maturation to to a certain level indeed so there are options there also for interaction for sure. I think one uh one factor the final factor that we uh we want to mention by the way this is uh all based on also a topic that we explored in a recent white paper that we published so that's why we we go in this certain direction of course but we we have the factors of um the biofilm we have the factors of the immune of the immune function but there's one very important factor that's also influencing uh this whole um uh topic of resilience and that is the the the saliva mm-hmm the importance of saliva because maybe maybe you could um elaborate a little bit on the on what is the role of saliva and and how can it support resilience both in a in a healthy and in a diseased uh dysbiosis state saliva is is often they say that it's a mirror of systemic health yeah so a lot of the saliva is being more and more used as a diagnostic marker for for several systemic diseases so it's actually a very active product which is composed of of a lot of metabolites that come in close contact with your biofilms. So saliva has uh an important for instance buffering capacity it's uh an important mediator to to regulate uh inflammation so if if your saliva is is buffering well your biofilm is is most of the time from a 2TK uh perspective in eubiotic state yeah what you clearly see is if you have patients where for instance the the saliva flow salivary flow is reduced like cirrostomia then you see that these biofilms way go way easier

Saliva As A Buffer And A Signal

Prof. Wim Teughels 25:50

to a dysbiotic state so that actually shows that your your saliva um amount but also probably quality yeah is very important in in keeping your eubiotic state of of your biofilm makes sense yeah so same goes with with with in diabetic patients we know that these these diabetic patients are more susceptible to certain certain oral diseases which relate on one hand obviously to systemic inflammation but also to changes in in in biof in saliva recomposition we have discussed about the ore microbiome you talked about one of its ability uh so the resilience um however I would like uh to tackle one of your core interests um one of your research interests which is actually what you said the modulation of the ore microbiome can you tell us uh why why you would you be interested in modulating or microbiome and what's the goal uh for me the I find oral biofilm modulation of the sorry this is my my baby this is one of the poolest things that that exists there and and it it comes a little bit from the aspect that as a clinician I realized that I could not sterilize the oral cavity I understood that actually the biofilm which is there has a really protective role that we have to start thinking alternative ways because obviously everybody knows about the antibiotic resistance but we start to realize and the data are getting really really clear there is also something which is called antiseptic resistance that is and developing so there should come new ways in order to modulate and especially with the whole um ecological hypothesis it became clear to me that that we have to balance more and more these these uh these biofilms because they are protective on their own I have enough patients again I already took the example that are 60 70 years old where the hygiene is bad and they don't have any disease and it's actually very protective. So a little bit by coincidence I ended up in in in the probiotic research in I mean the initial research that I did was on microbial interactions the crosstalk what could they do? It easily went into what is now being translated as probiotics work. Then you start that okay what am I doing modulating biofilms so you start to look further but there's also this prebiotics concept the postbiotics the symbiotics then you find predatory bacteria then you find stories about people who do fecal microbiome transplantations so you start to imagine that maybe people will do oral microbiome transplantation in the future and suddenly you're surrounded with all sorts of treatments that are all focusing on keeping the oral microbial number in check keep keeping them in balance and bringing these biotic states back to symbiotic states um or to eubiotic states without really without really focusing on what are the are there still pathogens or not? Again I I don't care about the fact that there are still pathogens or not. I care about what is the balance is there are there more beneficial species than than than pathogens and does it influence inflammation? Is there a low grade of inflammation? And as long as I have patients that have a lot of black with low amounts of inflammation and I'm I even was saying to my students uh two days ago that I don't care that the oral hygiene of these patients

Why Modulate The Oral Microbiome

Prof. Wim Teughels 29:55

is not optimal there is no inflammation everything is in balance the the oral microbiome is happy the host is happy so why should we change this? It's fine. So you're approaching the microbiome more from a health health point of view than focusing on the disease point of view. It circles nicely back to what we mentioned in the beginning of course with the whole paradigm shift it's yeah it is it is not focusing on the pathogens it is stabilizing the if if the the situation is a healthy state uh situation is stabilizing the oral microbiome making sure that if there is a factor that could push towards this biosis that the microbiome has enough resilience to withstand that uh that push yeah the challenge yeah so it this could be that that even sometimes the patient says okay I have a more stressful period in my life then we have to make sure that I mean this is a trigger to go into this biosis very clearly that that the microbiome can can withstand that that trigger and and that it's resilient enough to for a few days or a few weeks can withstand the trigger to to go into this biosis. But this is something that is is emerging it's it's not that easy um and it it's trying to figure out okay which are the factors where we can work on with this patient and how can we strengthen this. And there the the most developed domains are at the moment for sure the probiotics the prebiotics is is is an emerging domain but also there we get we are getting more and more positive results. And that is the way how but also even with with certain antiseptics I have to be honest I'm not completely against antiseptic but there are antiseptics where we have shown in our own group that they are actually pretty well in in preventing a dysbiotic shift rather than than just being used to to kill they actually can prevent these these shifts.

Rachel Chau, DDS 32:10

But it's also a matter of using the antiseptics in a strategic way because we cannot just say no antisepti it depends on indications.

Prof. Wim Teughels 32:20

You really have to know the the indication and and what to use when the problem is there are no guidelines around it. It's extremely difficult. It's an extremely difficult field also so finding the right antiseptic for the right indication there are some some things I mean after surgery after tooth extraction obviously that that's our the very clear the very clear uh indication when to use a an antiseptic boundaries but when we go into daily healthcare prevention then it becomes already a way more difficult difficult story. So honestly for me in in my own practice with with patients I really play with with the three factors which are the probiotics the antimicrobials although I use the antimicrobials there in order

Probiotics Vs Postbiotics In Real Products

Prof. Wim Teughels 33:20

to improve the effect of the the probiotics and the prebiotics maybe we can come back to these uh superbenes that you just mentioned probiotics prebiotics but maybe can you just start with the basics redefining first the probiotics for our audience uh their mode of actions what they do a lot of these terms that handle on on the word biotics and you have probiotics prebiotics postbiotics and symbiotics a whole bunch of things that are actually very difficult from from each other and and you really need to understand what are the differences in order to understand what products can do and and which products could deliver what they promise. So the the best known work is the word probiotics and uh when we talk about probiotics we are talking about products that contain living bacteria with beneficial effects on general health oral health now beneficial is is is a little bit double in the sense that they can be there in a dormant state but still if they are rehydrated they will become metabolically active and they are alive. This is in complete uh contradictory or opposite of something which we call postbiotics so postbiotics are products that also contain bacteria but they are in a dead state and these are products that uh you could ask yourself but yeah but why would you give uh a patient dead bacteria it doesn't make any sense well there are two two reasons for that one of them is that the fact that these dead bacteria can actually by their the products that are in in in in in the product by the uh with their cell wall composition they can already stimulate the uh inflammatory responses in a certain direction that's one thing second thing while they are preparing these postbiotics they are often producing all sorts of antimicrobials which can be in the product in the postbiotic product it's maintained in there the big advantage for for companies with with working with postbiotics is that in terms of stability in terms of uh production it it becomes way easier because you can include a postbiotic in a toothpaste or in a mouth which is an easy format that the the patient understands and is is used to using. And that's something that's not possible with a brome it's not possible with the current probiotics or unless you're going to use very fancy techniques and then you're going to have a toothpaste which costs about 100 euros for one one toothpaste, which is impossible. So basically all the products which are on the market that are toothpaste and that claim that they're a probiotic toothpaste unless the toothpaste is yogurt and has a shelf life of two weeks it will be a postbiotic which is fine. I mean it it doesn't matter it's it's just another concept another way of interacting. If we are really talking about probiotic supplements probiotic products it is almost all of the time in a tablet form in a in a powder form something which needs to be rehydrated basically probiotics work on on the two parts of um oral disease can work on the oral microbiome that's one thing and on the host is is the second uh part so in terms of of what effects have been shown on the oral microbiome is that uh these probiotics can actively produce antimicrobials I mean don't forget that that current penicillin was actually a uh something which was was produced by a fungus right so for these probiotic bacteria they produce all sorts of antimicrobial substances that can actually kill um bacteria pathogenic bacteria that are living around them that's one thing on the other hand they can interfere with the colonization of other pathogens they can influence uh virulence um gene expression of other pathogens so all the aspects of of which are taking place in a uh in a biofilm are influenced or can be influenced by is probiotic bacteria it is not that one probiotic strain will do all of these effects it's really strain dependent what they are doing but they clearly can interfere with the microbiome that is very clear. Maybe for the audience who do not understand the whole species genus uh type of differentiation of bacteria what exactly um would you how would you explain a strain specific activity like for example the ones that you used in your research yeah so strains if if we look at bacteria obviously they have names yeah uh so we are talking about Streptococcus mutants porphyromonas gingivalis so this Streptococcus or porphyronus is the genus and mutants or gingivalis is the species but it is a little bit like the genus would be we're all human and the species we are men but Martin you know you and I we are completely different men. Yes yeah we don't look the same so we should ask her we should ask Rachel but I think she will agree. We don't go there I don't want to go there. So and this is a strain difference. So the individuality is the spray the strain level and so within the postphilbonas gingivalis group or within the streptococcus mutants group you have different strains and they all behave completely different. They are as different as you and me this is also reflected in probiotics

Strain Specific Effects And Guideline Confusion

Prof. Wim Teughels 39:40

so it's it's very it's very nicely shown in um the gastrointestinal field that if you take for instance uh a lactobus plantarum probiotic and you look at its effect on irritable bowel syndrome that one strain can be very effective in reducing diarrhea in reducing abdominal pain while if you give the other strain also it's also lactobus lactobusculus plantarum it actually increases abdominal pains it increases um stomachache and and and diarrhea so selecting the right strain up to a strain level is extremely extremely difficult and it's often forgotten in in literature and and in in daily practice.

Rachel Chau, DDS 40:30

But then referring to what we are just saying and appealing to your clinician uh activity this um uh difference of activities of strains does it relate somehow or or can you explain how the that could maybe impact the EFP uh position on probiotics because the EFP mentioned or in the recent guidelines they said that um the probiotics are not necessarily recommended because it might not be have an additional uh effect as an adjunct to uh subting instrumentation and they don't even know if there is any effect in controlling the inflammation. But maybe you can give us your input on that considering what you just said about the different activities of strains.

Prof. Wim Teughels 41:18

Because I think this is a a major flaw in in the EFP uh guideline. That is what they actually did and and it it's a very logical step but it shows that you don't really understand how probiotics work. They actually took all the literature they had on probiotics because it was called a probiotic and they just threw it on one pile and did it some meta-analysis and they they looked at the effect and they saw there is no statistically significant effect. That is what they did. Now I was just explaining to you guys look there is there are differences it's not because something which is called a probiotic that it's actually effective for all of the diseases so the big problem with EFP meta-analysis which is uh the basis of um this this guideline is that they combine probiotic I'm not even going to say strains species that we know that are not effective for periodontal disease they can be effective for 2 decay and not for periodontal disease and they combine it with uh species that are effective for periodontal disease so if you would separate those out those studies that use species where we know that they're effective for peariodontal disease then you see that there is a highly significant effect but they just threw it together. And actually if you go to the original meta-analysis of Nikos Donos where that they used to make this uh consensus statement then actually Nikos wrote down that he saw for certain probiotic species I remember sentence yes clearly clearly that there was a better performance train yeah now this makes that that we are facing actually a very strange situation within the EFP because what you might not know is that actually in the recent EFP clinical practice guidelines for periimplant mucositis they are actually saying that the use of probiotics can help in the prevention and in the treatment of periimplant mucositis. Was it because you were part of the meta-analysis this time or no actually no so in both met uh in in in both consensus meetings I was not involved in in the analysis of this data which is logical in the one where they voted against probiotics I was present in the ones where I was not present they voted in favor of the probiotics now what is the difference between the both things it is that the period Mucositis, by coincidence, all of the clinical trials were done with one probiotic strain and species where we know that from a periodontal point of view it's effective. So it's a pure coincidence. All of these studies were done with that probiotic strain. Right. And then you clearly can see that should have been that analysis, it should have been a sub-analysis of the uh of probably the meta-analysis in the EFP guideline was done technically perfect. Yeah. But it was flawed from the beginning because they threw everything on one pile, whereas that they should have started with um putting data apart. I'm I'm very critical. So I'm not happy with the EFP practice guideline about we do not recommend to use probiotics as an adjunct to non-surgical parallel therapy. But I'm also not completely happy with the guideline that, okay, we suggest to use probiotics, because what they should say is they should specify the species, at least the species. So it's not now that it's like now they say, okay, you can take whatever probiotic and it will help against peripherucositis. No way. It will depend on the species, it will be probably depend on the strait, it might even depend on how the manufacturer makes the product, and it even more and more data seems to indicate that it might even depend on the patient. That not every patient responds in the same way to the same probiotic. A lot of work ahead for the uh revision that will happen in a few years, probably. It will have uh yeah. It will be another fight. But I mean for me, what is at the moment the most important thing is that by that time that there are way more clinical trials that can support or disapprove the effect so we can have a have a better idea, better view on what's working, um what's not working, and also especially how should we work BT sticks because it's not like popping on antibiotic tablet. A probiotic is is more complex in in terms of of its use.

Rachel Chau, DDS 46:04

Maybe we can detail that because it looks like indeed on probiotics we have a lot of uh of studies, a lot of research that has already been been known. One of the most uh famous supplements, probably. But you said prebiotics may work differently. So can you detail

Prebiotics That Feed The Right Bacteria

Rachel Chau, DDS 46:20

that?

Prof. Wim Teughels 46:21

So what are prebiotics? Prebiotics are actually substrates that uh sweet are not living bacteria, it's it's could sweet as food for bacteria that is being given to an ecology in order to stimulate the growth and the or and or the metabolic activity of beneficial bacteria that are already present in that ecology. So it's a little bit like giving a fertilizer to grass. I think that that's the best way I've heard um to describe prebiotics. And in a way, it's a super interesting concept because it takes away one of the downsides or the difficulties of probiotics. One of the difficulties of probiotics is getting them into the oral cavity and letting them colonize there. And we know that colonization is not permanent with probiotics. With prebiotics, you actually have already the beneficial bacteria being part of that ecology, so they're always there, just stimulating their growth or you're stimulating their metabolic uh activity. So that really differentiates probiotics from prebiotics. Now, finding prebiotics that interact with the microbiome is, in my opinion, way more difficult than probiotics. Because probiotics you can throw in whatever you want. With prebiotics, you have to be really careful that you're not stimulating wrong patterns. The bad ones and the bad ones as well, maybe. And the bad ones as well. Because I mean, now I'm going to say something very controversial. But if you want to prevent periodontal disease, the best prebiotic would be to give your patients high doses of sucrose. Because the high doses of sucrose will acidify the environment. The periodontal pathogens will not like that and they will not grow. They will be really unchecked. But what you get in return is rampant carriers, there we go. Radical carrier. So this is, I mean, don't take now sucrose, don't tell me uh Wim Teughels I said that that sucrose is a prebiotic, don't use, but it's it's the concept which which is there. So finding the right prebiotic supplements is uh it's tricky and and difficult. Maybe then do you have another example than sucrose just to I'd been been doing uh research myself on on prebiotics, but often these newer molecules are quite expensive. So the the ones which are on the market at the moment and which are affordable and and um seem to work are for instance um nitrate. This is one of the the very uh very emerging prebiotic, and then we have the L-arginine of uh some some um commercial companies that really seem to they they primarily work on on buffered pHs. That that is their major uh, especially the allarginine. When we go to nitrate, for nitrate the story is a little bit different in the sense that it goes into stimulating nitrate-reducing bacteria that are associated with health that can also help in buffering. But the super nice part of nitrate is that um the nitrate-reducing bacteria, the beneficial bacteria, are actually involved in something which is called the nitrate, nitrite, nitric oxide pathway. And that becomes really important because the end product of this pathway is nitric oxide, which is extremely important for general health. So it controls blood pressure, it is important in wound healing, and so on. So, what I am telling here is that the oral microbiome and the nitrate reducers in the oral cavity are actually connected to systemic health. And by promoting them with a prebiotic, with the nitrate, you actually could not only improve oral health, but you would also be able to improve systemic health, general health, preventive.

Nitrate Pathway And Nitric Oxide Benefits

Prof. Wim Teughels 50:45

So not only by when there is disease, you try to improve oral health, because we know about the oral health, systemic health link, but actually by stimulating the oral microbiome, specific parts of that oral micro, you actually could create a uh eubiotic state, but not only for orally, but also systemic benefits. And this nitrate, nitrite, nitric oxide pathway, it's only possible because of the oral pathogen uh the oral bacteria. It's incredible. It's it's an incredible system. I I don't know why anybody didn't think or realize this earlier, but actually the system is that um this is the breakdown pathway. So you have nitrate, which you get from the green vegetables. When Martin, when your mother said Martin, eat your green vegetables, she was really right, it's important. Nitrate is being converted to uh nitrite that goes through through uh the stomach, but the nitrite cannot be converted to um so nitrate, nitrite, nitrite to nitric oxide is not uh not possible. So what is it's being done is that uh the it's being recycled through the kidneys and it goes back to the the saliva, and there the the nitrate is being uh exposed to the ore bacteria, the nitrate reducers who bring it to nitrite, and nitrite is then later on uh taken up again into the stomach and comes in the circle uh systemic circulation and becomes reduced to nitric oxide with all of its benefits. But there are no cells in the human body that that can do this. The only place where this happens is in your cavity. And that is, for instance, this is shown in several studies where when you use broad spectrum antimicrobials that actually bluntly kill all of the bacteria in the cavity, you could see that these patients have increased blood pressures. Also, don't see normally if you have been doing some some workout, you have a uh a post-workout hypotension, your blood pressure goes down. But this is not happening with patients that use very broad, very aggressive uh antiseptics. And we also know from a Mexican uh survey or Mexican study that people who use frequently use antiseptic maltruses, and this was uh determined to be three times a day or more, they actually have higher risks to develop diabetes and several systemic autosystemic diseases that are related to reduced nitric oxide um situations. Incredibly fascinating. So the the link of these nitrate reducers and with systemic health and and the cavity is extremely important. Yeah. I I have one last point on the on the prebiotics topic. Uh you mentioned that for the postbiotics, usually when you see toothpaste or a mouthwash that claims it's a probiotic, it's actually postbiotic because probiotics cannot be delivered in these types of products. How is that with prebiotics? What is the usually usually the mode of delivery? I I well you already mentioned nite nitrates being consumed through through vegetables. You know, but how how how does it work for more the I would say artificially produced prebiotics? I think I mean if if we think about oral health, these are typical products that can be delivered in crude piece amount. That would be a very logical uh way mode of application. So it's topical, topical application. This is the the way I would go unless we really can have proof that the GI microbiome is really influencing the oral microbiome. But then we need to go for completely different prebiotics. So, for instance, for the GI microbiome, uh the gastrointestinal microbiome, the prebiotics are often fiber prebiotics. Yeah um and this Gaussal FOSS. The issue is there that it takes the microbiome a long time to really digest them and cut it out in different pieces. This is there, the microbiome is different because the passing time is really short. So you need to have other prebiotics that are fastly metabolized or taking on by in your biofilm or biobacteria. So, therefore, a topical local application of a prebiotic is the way to not the typical prebiotics for GI health.

Rachel Chau, DDS 55:20

But it seems like, yeah, prebiotics have their advantages, like probiotics, but somehow probably we you can combine them into what we heard as it means cosybiotics, but there are these combinations, but maybe also with other micronutrients, or what's your take on that?

Prof. Wim Teughels 55:38

The symbiotic is is one of, again, these biotic takes, and it means that you combine a probiotic and a prebiotic. Now, the combination can be done for two reasons. So one reason can can be that the prebiotic is uh stimulating the probiotic, so it's specifically there for uh the probiotic. Another reason can be that you just have a probiotic and you have a prebiotic which do not interact with each other, but you use them for another one. So these these are the differences. Next to that,

Symbiotics Micronutrients And Patient Differences

Prof. Wim Teughels 56:10

there are a whole bunch of uh of micronutrients where we in in literature have some evidence that they actually can help in modulating microbiome, but also most of the time steering inflammation. We should not forget that, especially when we're talking about periodontitis, periodontitis is actually a group name of, at least that's how I look at it, of different diseases that have the same clinical image, bone loss around teeth. But it's not one disease entity. I mean, it can be that for one patient, it can be because the the patient is is has a low uh for the vitamin D or vitamin C score. That is something which is is very well known, and and I also see this in my patients. So often when I see, I'm not going to say the the the old, I mean old, the 60-65-year-old uh patient who comes in with severe periodontitis, okay, that's something else. But if if the the 35-40-year-old uh person comes in with periodontitis, I actually do a uh blood screen, and I screen for the micronutrients, for for vitamins uh and the presence. And often you see, especially in in our countries when there is not a lot of sun, um exactly winter time, you see that the vitamin D depletion is often there. And we have a lot of of evidence that that shows that vitamin D is really important in um strengthening the immune response. Probably works through the immune system. It works through the immune system. So combining these supplements together with with prebiotics is for me a very logical, logical step. Um, because we cannot, based on the clinical picture we get from parallelitis, it's extremely difficult to find out what is now the etiological component in this patient. Is it a depletion in micronutrients? Is it uh a hyper responsive uh inflammatory response? Is it a hypoinflammatory inflammatory? Is it uh certain microbial perturbation? Even viral infections have been described in in the literature? So it's it it's very, very complex. So by supplementing with these these products with with micronutrients, you could, based on the literature, you could improve their effectiveness. For me, this is a very logical step and a very logical combination.

Rachel Chau, DDS 58:49

Still for the moment a budding uh area of research, like some something still uh in development, not necessarily.

Prof. Wim Teughels 58:57

Oh, yes, Rachel. I have to admit that what I'm talking now about is really something which is emerging over, I mean, for the the big public over the past five years. I know I'm working in on probiotics for 25 years now. We we're pioneering that, but now in the meantime, the prebiotics, the micronutrients are coming, and people start indeed to understand that it's this ecological balance, and that the way how we were working in the past that's not going to work anymore. So it's under development, but I'm quite sure that within the next five to ten years you will see way more and more these products popping up, these approaches coming, and the only thing what I'm hoping is that the products that will pop up and the approaches that are coming, that these are backed with science. Because one of the big problems that these pro microbials pro microbial therapies are suffering from is that there is this connotation that this is based on pseudoscience, which is not the case at all. Many of the claims are really based on on actual research evidence, but you need to be willing to look for it, to understand it, and then you will see that it's it's not some hocus pocus. And the the the whole field of pro and pre-biotics, it's what's happening now. Maybe as a final question, how do you see the future? What I see there's a difference between what I see and what I hope, but obviously I think what I see for sure is that we are going to go for sure in the direction of microbiome modulation and host modulation. Way more as a preventive measure and as a treatment measure, way more than just killing bacteria. I see that in the future we probably as dentists or healthcare uh workers will not be able to use any antibiotics anymore. And I feel even that they're going to restrict certain antiseptics. So we're going to be blocked there. Where I envisioned this is going is um this will be going, and I know people are

The Future Personalized Microbiome Care

Prof. Wim Teughels 1:01:20

using this word already from when I was still a dental student, universalized medicine. This is one of these words that we love to use back in the 2000s, 2010s, but nothing really happened. We are still treating our patients with the same techniques which are effective for most of them, but for certain notes. Now, what I see at least in the probiotic field, I'm I'm I have to be careful with the prebiotic field, is that we see that these probiotics are can also be host-specific. So it means that if we treat you here would be using a probiotic, it might be that it is effective in Rachel. It's effective in you, Martin, but they are not colonizing my oral cavity. So in a way, I I think that in the future we might find ways to figure out which probiotics are more for your health, which probiotics are more indicated for my health, not only for what they're doing, but also in terms of compatibility with my criminal health, and which ones are for you, Richard. So that is where I think we are going. Sounds like taking the paradigm shift a step further and more and more also considering the whole host uh relationship. It is because it's for sure. I mean, whenever I'm talking about oral health, in my mind it's immediately connected to systemic health. Oral health and systemic health are for me one and the same. Obviously, I'm I'm a dentist, I'm a peraleontologist, so I'm more relaxed in talking about oral health. But by improving this, by improving the resilience, by improving the microbial balances in the oral cavity, if I see what momentum we are in now and how research groups are starting to focus more and more on these ecosystems, it will not take a long time before our friends of the gastrointestinal field will be looking at the oral microbiome to get ideas. Yeah. Stop being people ask me what is happening in in the GI field in terms of but actually the big advantage that we have in in the oral field is that we can easily sample. We can learn it's so reachable. And this is what often the the the castor and envy us. Because for them to take a sample We all know where that's going. Okay. I don't have to explain that. Good. No, but it's true, yeah. We have a very fascinating environment. And patients who are regularly seen by professionals as well. And I think it's more fun to be seen by a dentist than by a gastroenterologist. I mean, many of our practition the practitioners are convinced of that. Um that is not not something that I think. I think the big challenge will be the opposite for the general practitioners, the the the uh gastroenterologists, the medical doctors to convince them about how important the cavity is for their own speciality. I think that is the challenge for for the coming years. Yeah. I think it's a nice closing uh remark, right?

Rachel Chau, DDS 1:04:28

On this note, I think we can uh come to a close to our conversation with you, uh Wim. Thank you so much for this exchange and for sharing your knowledge and insights with us and with our audience. It's been a real pleasure. Thank you all for tuning in and for being with us with uh this episode on the Ormacoparium with Professor Wim Teughels. We hope that you could leverage some of the insights shared with us by our expert and that you can use that in your daily practice. We will be back soon with a next episode with a new guest and a new topic. Until then, thank you so much for being with us and see you soon.