The Oral-Systemic Connection

Periodontal disease touches nearly every part of whole-body health.

In this episode of Let’s Talk Oral Health by GUM ®, hosts Rachel Chau, DDS and Martijn Verhulst, PhD (Sunstar) sit down with a household name in the world of periodontology, Professor Emeritus Bruno Loos. Together, they dive into the fascinating and irrefutable intersection of oral health and systemic diseases. The conversation also explores emerging insights on inflammation, immune fitness, and how trends like Ozempic and artificial intelligence may reshape the future of periodontal care.

Transcript

Welcome & Guest Introduction

Rachel Chau, DDS 0:18

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, Martin Verhulst. Hello. Hello, Martin. Today we are diving into the fascinating intersection of oral health and systemic diseases. And for that, we are very happy to welcome a household name in the world of periodontology and an expert in periodontal medicine. I'm talking about Professor Bruno Loos.

Prof. Bruno Loos 0:49

All right.

Rachel Chau, DDS 0:50

Hello Bruno.

Prof. Bruno Loos 0:51

Hi. Thank you for inviting me.

Rachel Chau, DDS 0:52

Thank you for being with us. We are thrilled to have this conversation with you.

Prof. Bruno Loos 0:56

Yeah. Thank you for inviting me and having me here and seeing the headquarters here in Switzerland.

Rachel Chau, DDS 1:04

I think you have uh you had a small glimpse of the uh the vibe with in the building with the Japanese uh paintings, the Japanese VIP room. So you understood that Sunstar has Japanese origin, and with that, it has actually an intrinsic holistic approach to all health. So you are a professor emeritus at ACTA in the Netherlands.

Prof. Bruno Loos 1:28

Yes.

Rachel Chau, DDS 1:28

So ACTA being the academy of dentistry uh over there. Tell us a bit more about your uh your your your background.

Prof. Bruno Loos 1:36

So, okay, thank you. Um yeah, I'm I'm Professor Emeritus in periodontology and from ACTA, and ACTA is actually the academic center of dentistry in Amsterdam. And uh I've been working there for 32 years in the department of periodontology, and um I have been engaged, of course, in in teaching and research and uh patient care in the department, and um and also teaching a lot for postgraduate students, becoming a periodontist, and um yeah, with a lot of pleasure and still ongoing with current uh PhD students.

Martijn Verhulst, PhD 2:17

Yeah, and before your time in ACTA, um you also spent some time in the US, if I'm not mistaken. Could you maybe share in a few sentences what uh what you did?

Prof. Bruno Loos 2:26

That was a long time ago. Uh I did my um um periodontal training in the US, and uh after my clinical training for three and a half years, I uh went to um the State University of New York in Buffalo, Buffalo University and uh Department of Oral Biology, and there I did my PhD, right? And I studied also oral biology.

Rachel Chau, DDS 2:50

And I understand that ACTA is actually what links you two together because there is some sort of a special bond between the two of you. So Martin, maybe you can tell us a bit more about that.

Integrating Oral Care into Diabetes Treatment

Martijn Verhulst, PhD 2:59

Yeah, sure. I mean, uh it's true. Um before I joined Sunstar Company, I was um doing my PhD research in ACTA, and that was under supervision of Bruno. Um, so I always say I have actually two fathers, my biological father and my academic father, and Bruno is my academic father. So um, yeah, for me it's a very nice uh opportunity to also work together again after 10 years when I started my PhD research, and now we are back in the same uh yeah, same environment. And I remember from my time in ACTA, there was always um we had we used to have these weekly meetings, you know, uh to discuss progress with the research. And it was always Bruno asking me whether we were sitting alone or with colleagues, it was always Martijn. Can you maybe explain again what are you doing with your research? Uh, can you maybe repeat what are you trying to investigate? What are you trying to show? And every week it was the same. And to to me, at times that was a bit annoying because um you know you had to repeat yourself every time, and I was thinking, doesn't he even get what I'm what I'm actually doing? But then later I found out there was, of course, a way to keep you sharp and keep the sort of the focus on on what you're doing, and and you need to be able to always explain what you're doing, and that's actually very nice because that's exactly what we're going to do today. Because this time I'm not the one who's being uh asked, can you tell us what you do? But we're going to ask Bruno.

Rachel Chau, DDS 4:19

Yeah, but maybe we can start with you. What were you doing?

Martijn Verhulst, PhD 4:22

That's a good point, yes. Exactly. So um, my uh my research was focusing on the as Bruno's research always does on the oral systemic link. Um, and we were investigating um whether we could implement an oral care protocol in diabetes care, so in primary diabetes care with family physicians, and see if we can bring the two disciplines of medical care and oral care closer together, work closer together, and then see what does that actually mean for the patient. Um, and in the end, we found that when you actually do that, you can achieve improvement in quality of life of the patient because that was the the primary outcome of the research. Um, and we did several other projects related to uh to the oral systemic link, but that that was really the the key focus of the research. Um, trying to yeah, to to bring the two disciplines of medical and dental care together, and instead of working in silos, try to work as one task force for the benefit of the patient, and that was actually what we uh what we showed.

Prof. Bruno Loos 5:25

So, yeah, it was uh I think um a very unique uh project because we really worked together with um 22, I think, family 24 uh practices, family doctor practices, yeah, and uh family physicians. It was uh it was very good, and um and it was an RCT, yeah, a randomized controlled trial, so it was nicely set up. Yeah.

Martijn Verhulst, PhD 5:52

So yeah, it was a lot of work, but it was uh worth it.

The Irrefutable Link: Type 2 Diabetes & Periodontitis

Rachel Chau, DDS 5:55

So but it's like a reunion actually for you today, and the topic of your research is actually a nice entry point for our discussion because uh we are talking about the oral systemic link, and we know that the link between oral health and diabetes has been one of the most well-documented relationships, bi-directional relationships. And talking about all your uh experience at ACTA, your work, you have done a lot of work on this topic of diabetes, and you have published many dozens of papers on that. So, my first question to you, Bruno, would be could you maybe unpack uh for us all the most important learnings uh after all these years of research on the topic?

Prof. Bruno Loos 6:44

Um no, but I think in in terms of the relationship with diabetes, um uh after all those years, the the relationship between uh diabetes, particularly type 2, and uh periodontitis has never been refuted, has only been strengthened. So it is very clear, and today we even better understand why uh this relationship exists. It's the fact that when people having uh diabetes type 2, and particularly when it has not been completely diagnosed or uh is in a prediabetic phase or poorly controlled, uh the patient is more susceptible for in inflammatory conditions, in infections in everywhere in the body, and also blood vessels may be um uh affected, and uh the whole immune system is affected. So, obviously, or logically, uh, we can also realize that when people have inflamed gums, that will worsen because of the diabetes, the diabetes type 2. So uh, and that means worsen uh periodontal inflammation and it will uh accelerate and uh the progression of the disease. So, that is uh to wrap up that we really understand, and it's not that difficult. The periodontitis in that respect is not different from another systemic disease or inflammatory process, it's negatively affected by uh poor diabetic control. So people with poor diabetic control will have more inflamed gums, will have uh progression of their periodontal disease, may have periodontal abscess formation, and uh unfortunately. So in recent years we even uh yeah think and research has shown that uh many people that have been uh referred to our clinic for periodontal disease and periodontal treatment uh may have a state of prediabetes or even diabetes while they are unaware of it. So in our clinic, having these patients it may be a sign that they have diabetes. So we even shift that in the periodontal clinic you could theoretically identify new patients for the diabetes, having diabetes. So, yeah, I hope uh this is a very short uh summary, but the link uh is clearly uh present. Yeah, as and established it's very established, and and actually you have to realize that the prevalence of people with diabetes among patients with periodontitis is at least double as the as the prevalence in the general population.

Martijn Verhulst, PhD 9:49

Yeah. We always um talked about um periodontitis being one of the uh complications of diabetes, uh right. If you have diabetes because of the chronic inflammation, you see that you develop um I, you know, eye disease, eye disease kidney disease, um, neuropathy, so your nerves become damaged, and periodontitis fitted into that line of complications, and that was, I think, already introduced in the 90s. Um, but I also remember um when I was doing the research myself, and there was the moment in time where there was a lot of attention on the other way around of the association because now we're talking about diabetes being a risk factor for gum disease and for you know periodontal inflammation. But the direction is not just in that direction, there's always there's also another way around. Maybe you can elucidate a little bit on the on that direction also.

Prof. Bruno Loos 10:38

Yeah, I think um uh we have to realize that any form of chronic inflammatory condition in the body can disturb the metabolic condition and uh balance in the body, and uh can disturb you can say the sugar levels and the levels of insulin, and and uh can increase the uh insulin resistance that is found in uh diabetes. So having an untreated inflammatory condition, including periodontitis, may uh speed up or worsen the pre-diabetic phase into uh full blown diabetes, or having people not having diabetes maybe speed up uh their um their movement towards having pre-diabetes. So, uh yes, indeed. In periodontitis is not unique. I I want to stress that it is it it should be it is something for other inflammatory diseases as well. But of obviously, we are talking about oral diseases, and periodontitis is one of these that can uh worsen the metabolic condition and insulin resistance. Yep. So that is the the the two ways, and um, and even I know of an uh Korean study, a big large um epidemiological study that has shown that people um with periodontitis, um, you can see that they develop the the diabetes faster than the control group without uh periodontitis.

Martijn Verhulst, PhD 12:25

Maybe of the Korean uh enhanced equivalent study. Yes. Yeah. And I also remember when talking to the family physicians, sometimes they said, When I have a diabetes patient who's poorly controlled, and I'm doing everything I can, I'm doing as much as I can on diet, on physical activity, I'm even increasing uh the drugs, and you still struggle to get good glucose control, and then later they found out that there is a chronic inflammation in the mouth going on that sort of disturbs their treatment efficacy. And that again sort of emphasizes that you cannot ignore uh oral health when you are treating a patient um systemically. Yeah. And I think that was quite a nice uh yeah.

Prof. Bruno Loos 13:06

Yeah, it's an example of where uh the dentist and the physician um yeah, should work together. And uh the physician having his diabetic patient that he should or he she should ask, uh, have you been to a dentist lately? Have you been checked for gum disease, periodontitis, and uh vice versa, and uh a periodontist or a dentist who sees a patient with severe periodontitis should be aware that there might be underlying uh diabetes.

Martijn Verhulst, PhD 13:39

And there's of course the nice evidence that when you uh correct me if I'm wrong, but it's also I think in the EFP guidelines acknowledged that if you treat periodontitis in diabetic patients, it can result in an improvement in in glucose control. That's correct. Taking away the inflammation can really bring down the blood glucose in a way that is clinically relevant.

Prof. Bruno Loos 13:58

But it's actually not specifically the blood glucose, it's the ATOC and that has been reduced, although uh the literature uh shows it's it's significantly reduced, but it's never reduced to the level on average to the level um below the threshold of diabetes, unfortunately. But by the way, these studies have been very interesting, yeah, because uh the reduction in HBA1C due to periodontal treatment is uh about a half percent, and uh it has been recently confirmed by the Cochrane Institute also, and they claim there's no further intervention studies needed. Um but these this reduction in HBA1C is on top of their normal treatment, right? Because they uh people are recruited to have periodontitis and diabetes, they have a diagnosis of diabetes, they haven't been treated by their physician, and then we do the periodontal treatment, and then you get another uh reduction. So it's uh it's a powerful therapy, periodontal treatment.

Cardiovascular Disease & The Role of Oral Bacteria

Rachel Chau, DDS 15:07

But if you say diabetes has an irrefutable link to periodontitis, it's not the only one. Uh another focus of yours during your research was also cardiovascular diseases, which is also very much linked to a periodontal disease in general. Can you maybe also tell us about the evolution of the understanding of this link and where we are at now today?

Prof. Bruno Loos 15:31

Yeah. Yeah, I uh it's about um you can say 40 years ago that the first time it was mentioned that there might be a link between oral health or oral diseases, periodontitis, and cardiovascular diseases. And that was uh shocking, very interesting, of course, and uh made people much more aware. And um, over the years, many, many studies, cross-sectional and longitudinal studies, have continuously proven that there is a um association between oral health or oral diseases, actually, and um cardiovascular diseases. So that is also like the diabetes link, it is a link between and particularly the periodontitis and cardiovascular disease, is a link that should not anymore be uh doubted for. It is definitely existing. However, as we move through time and uh a more recent uh development is that on an epidemiological level we realize that it is not the whole periodontitis population that might have an association with cardiovascular disease. Within the periodontitis patients, there are subgroups, some or or some clusters or or silos or buckets, uh what Jim Beck calls them, of people that are much more um have a much bigger association and link with cardiovascular disease among these patients with periodontitis, and other patients um may have more links to other systemic diseases. So uh it is a challenge for the future to sort out which groups of periodontitis patients are more related have more the relationship with cardiovascular disease and diabetes versus a group that we have have found in recent years in research. A group of periodontitis patients has much more a um a link and associations with uh respiratory diseases and rheumatoid arthritis and other types of immune diseases. So it's um uh as we move forward in science, um we see that uh where we had in the past pulled all the patients together and had average scores, we would do find out that there's definitely individual differences, individual groups of people, rather than everybody the same. It's intuitively uh normal, but we didn't do it before. But now we can with more advanced statistical techniques we can cluster people and um and find these things out. By the way, there are also periodontitis patients not having a link between cardiovascular disease or the diabetes, luckily. Yeah, so that's another group of people.

Martijn Verhulst, PhD 18:41

Yeah, yeah. We're going to into the the underlying mechanistic discussion in uh in a few minutes, I suppose. But besides the besides these epidemiological studies, uh you also have quite quite some knowledge on um more the fundamental research behind uh this association between periodontal disease and cardiovascular disease. For example, peep researchers finding oral bacteria in the atheroscleroscleric. Um could you maybe shed a little bit of light on that before without going too much into detail on the underlying mechanisms, but uh some of the key findings that we that we did in the past uh decades on this association?

Prof. Bruno Loos 19:21

So the indeed, if you uh look back at the last uh 20 years, we have been trying to explain mechanistically uh how periodontitis can be associated with cardiovascular disease, and that was actually a quest towards a causal causality of periodontitis into peer into cardiovascular disease. And uh today I think we really better understand that like periodontitis, cardiovascular disease is also multi causal. There's multiple factors that work at the same time to eventually get uh get to the true disease event. It's not one thing, so it's not only bacteria coming from the mouth, uh, but it it is one of the explanations why uh atherosclerosis is atherosclerosis developing that there are bacteria from the oral cavity in the circulation, and they might uh dislodge into atherosclerotic lesions, and even if they are dead, their components can stimulate the immune system, can stimulate inflammation in the vessels, in the blood vessels, coronary arteries, for example, and um so that could worsen the uh atherosclerotic process. Uh but the oral bacteria are not the only bacteria that have been found in there are many types of bacteria found in atherosclerotic lesions, and mainly, and mostly they're not alive, they are dead, but somehow packaged into uh large macrophages and foam cells and giant cells, but can still have their mechanistically their LPS, their lipopolysaccharide or their endotoxins that can stimulate the immune system and exacerbate inflammation in such uh lesions. So, but that is one mechanism, but there's also the issue of uh say autoimmunity that uh because of the periodontitis, autoimmune cells develop, autoimmune antibodies uh develop. So there's various processes what can explain mechanistically um how the immune system in uh Is affected by periodontitis and having a negative effect on the um on the generation of atherosclerotic lesions and can worsen the situation. But let's um be fair. To me, uh causality of periodontitis to cardiovascular will never be found, even though there's overlapping genes and the mechanisms we talked about and the the inflammatory mediators that from the oral cavity spill into the circulation. It all adds up, but not per se that periodontitis is a causal uh problem because we didn't talk about cholesterol and exercise obesity. So the two diseases, what they do is they share uh genetic components, they share lifestyle factors, uh negative poorer lifestyle factors, and other aspects that why they co-occur.

Obesity as an Inflammatory Disease

Rachel Chau, DDS 23:02

I think that's actually the next segment that we're going to talk about uh the comorbidities, the fact that there are several diseases that can be um can actually work together, unfortunately, like diabetes, cardiovascular disease, and obesity, which is a comorbidity but also a disease by itself. And um maybe you can also you you talked about the mechanistic link uh between periodontal diseases and cardiovascular diseases, but it would be nice if you could also do that for the link between obesity and our health.

Martijn Verhulst, PhD 23:35

Yeah, yeah, and the role of obesity in the relationship between you know all those chronic diseases, it looks like it's all interconnected.

Prof. Bruno Loos 23:42

Yeah. And uh the thing is that obesity we can consider a disease, actually an inflammatory disease. Um uh in fact an inflammatory disease of the uh lipid tissues in the body, and particularly in inside the belly. Um so it the cells are chronically inflamed, and when they are chronically inflamed, we call them they are under stress, and they release uh many more pro-inflammatory cytokines. So you can say the the fat cells are not just qua just quiescent cells, they are very active and they pump out these pro-inflammatory mediators, and that uh, for example, can lead to insulin resistance, so that can induce diabetes. But uh the pro-inflammatory mediators are circulating in the body and they can uh can also affect the existing gingivitis or periodontitis and can worsen that chronic inflammation. So uh from obesity you can get an enhanced progression of periodontal disease, for example, of periodontitis, or worsened gingivitis, which is a huge risk factor for periodontitis.

The ""Ozempic"" Effect: GLP-1 and Oral Health

Rachel Chau, DDS 25:07

We understand the the the the link between uh excess body weight and and overall health, but which is actually interesting in the sense that we know that obesity is on the rise in the world. It's actually even more uh prevalent than famine, as you said earlier. So there is also now all sorts of uh uh treatments that are uh that are tried to uh to uh to cope with that issue. And one of the recent trends that is heading uh that are the headlines is the use of Ozempic to reduce uh the body, the weight. So can you tell us a bit more about what first how it how does OZIMPIC work?

Prof. Bruno Loos 25:50

Yeah, so OZMP is actually a uh synthetic or pharmaceutical agent that mimics uh a natural hormone in in the body, and the natural hormone is GLP1 that actually um is binding to a receptor, and when the receptor is uh activated by this natural hormone, it will give the person uh a feeling of um that he has enough, he ate enough, so uh that he is uh feeling not hungry anymore. So that's one aspect. Uh secondly, it is a um when the receptor is triggered, it um takes care of the uh it it'll say reduces uh reduces the pro-inflammatory mediator release of cells, so it works also anti-inflammatory, and in that way it also has an effect on the immune system. And uh because people or we think that people eat less because of that feeling of I'm not hungry anymore, uh they also lose weight. And the Ozempic is popular uh suddenly, although it is a medication for diabetes originally for diabetes, because it will increase the insulin production, it may help to people to lose weight, and uh maybe the loss of weight also helps to reduce inflammatory status, we don't know exactly, but it all comes together. So the analogue of the natural hormone binding to the receptor GLP1 RA receptor antagonist, that's the pharmaceutical analogue that uh mimics a natural hormone and uh has not only an effect on the insulin but also on the hunger feeling, on body weight, on immune systems. So suddenly it is very interesting because for people to lose weight, but also um it has an anti-inflammatory component to it, and that might be interesting even in the field of periodontitis or periodontology for uh yeah, reducing inflammation in general and maybe reducing the inflammation of periodontal lesions.

Martijn Verhulst, PhD 28:19

I was going to ask about that because uh I know I know you know there's some preliminary research and some in vitro and animal studies on the effect of Ozempic on on periodontal health. Um, are there some interesting trends or findings that could be interesting for the future?

Prof. Bruno Loos 28:36

Yeah, so um first of all, there's in vitro work. People have tested uh the the analogue, the drug uh in periodontal ligament cells, and uh when they are stimulated with a um inflammatory component, uh like LPS or endotoxins, they they pump out less amount of inflammatory mediators when there is also Ozempic uh present or the the analog. Ozempic is more the generic uh brand with which we should say the GLP1 RA. It's difficult to remember. Yeah, Ozempic is easier, yeah. But there are many uh semiglutide and others. Ozempic will be happy. Um and so uh and also uh there are um uh preclinical studies in in animals with an experimental periodontitis model where they show that the animals having uh the drug are showing less alveolar bone loss and less pocketing and less inflammation in the experimental periodontitis model. And also people have shown in a one, yeah, there are some very few clinical studies, but one clinical study where people with diabetes and periodontitis were treated for periodontal for the periodontitis, got periodontal treatment when they were on the Ozempic, their treatment was much more successful and their inflammatory status went down much better than when not on having the Ozempic. So it's uh it's it's a drug uh I call it a positive side effect. We as periodontists should not prescribe it, but uh when patients are having it or getting it prescribed from their physician, uh, and and if they have periodontitis, uh the periodontitis treatment will really add up uh in yeah, becoming more healthy, the patient.

Martijn Verhulst, PhD 30:33

Yeah, we we talked about this before today, of course, and um I I quite liked one um angle you mentioned is uh once a patient starts the treatment with Ozempic, that's sort of a milestone in his life or her life, um, where you start taking care, actually, prop proper care of your of your health, of your overall health, um, which may then also be a nice reminder or a good starting point for a professional in the oral care field to remind them. Don't forget if you now start taking care of your uh systemic health, why not also start to boost that by also starting to take care of your of your oral health? Because it's uh it's as we said now several times, it's linked. Yeah. So it could be yeah, I quite like that that that approach you mentioned of.

Prof. Bruno Loos 31:22

Yeah, I think that that that is uh is good, and and also the use of uh or the the better oral health uh care the patients have, brushing and and interdental care um is a moment that uh taking the Ozempic, having the treatment for periodontitis, becoming more healthy, losing weight, and then uh also improving your own oral health by better oral health care at home, daily oral health care.

Rachel Chau, DDS 31:52

That would also uh support the in dis interdisciplinary care of the patients. Yeah. Because as you said, Ozempic is not prescribed and should not be prescribed by dentists. So it should also be in the in the speech of the of the physician uh to take care of the of the gums, basically.

Prof. Bruno Loos 32:10

Yeah. It would be good if if physicians realized that uh the drug that they prescribed would have beneficial effects also for gum disease. Definitely. But we should be careful, it is preliminary work and uh we have not a lot of data. No. But it is a uh interesting drug with you can say positive side effects and doesn't harm the period periodontum. No.

Understanding ""Immune Fitness"" and Lifestyle Coaching

Rachel Chau, DDS 32:39

Even though it's a hypothesis, you still uh said that there is this anti-inflammatory uh side effects of Ozempic or GLP one that could be interesting, which leads us to the common denominator of all these uh chronic diseases and periodontal diseases, which is inflammation. And with inflammation, there are also um the biomarkers of inflammation that we could also now screen. But before we go into the biomarkers and which are the most uh well-established or well known, um inflammation is also linked to the concept of immunity, as you said, and the immunity fitness particularly. So maybe let's start by define what you mean by immune fitness.

Prof. Bruno Loos 33:24

Yeah, and it's a term that um I have uh seen in the literature, the general immunology literature, and uh it is a term that that really helps to understand the that your immune system or your host response the way you wanna call it, uh has a certain le can have a certain level of fitness. People know about physical fitness, they go to the gym, etc. But your uh immune system can also be trained and boosted and uh and be performing well, and that I call uh immune fitness. There are many aspects that uh can affect immune fitness. Let's take a few examples. If you uh have um uh a poor diet, for example, very little fruit, uh, so you have very low levels of vitamin C, then your immune fitness will be uh lower. If you are uh short of vitamin D, for example, your immune fitness might be lower. And uh whenever you have in your system inflammation, like from obesity, your immune fitness may be lower. So there are many aspects in the lifestyle part, but also unfortunately in the genetic part that determine a certain level of immune fitness per person. You can do something about it. You can um you can boost your immune fitness again by having a good diet, by losing weight, by stop smoking. Those are all aspects that help to boost your immune fitness. And uh so it's a term that I have been using for um also in my patient care. And they say, ah, okay, so that is something I can do myself. And um your immune fit say there are three clusters within the total multicausality of periodontitis: the genetics, the lifestyles, and having a unfortunately in systemic disease or condition. Those three determine the level of your immune fitness. Controlling your systemic disease is one aspect, like diap controlling diabetes, but uh in the lifestyle part, you can uh people can stop smoking, lose weight, so bec uh take care of a good diet, and there are many more aspects, having less stress, etc. That all of it can boost the immune fitness. So it's it's a term that um that makes it understandable and uh and is useful. But I didn't invent it, I I picked it from the immune immunologist.

Martijn Verhulst, PhD 36:19

Yeah. Yeah, we often talk about uh also in you know in in internally in our company and in our in our content articles, we all often talk about the concept of immune fitness. Um, but what can what is the role of oral care professionals in trying to work on the immune fitness? You mentioned mentioned a few clusters, but of course, uh a hygienist or a periodontist or a general dentist. They're not per se lifestyle experts. They of course only have a limited time with the patient. And so, uh what what would you would be your recommendation on how to make the most of uh of the possibility of of you know they are there in in frequent contact with the patient. How how to leverage that time to work on those uh those clusters?

Prof. Bruno Loos 37:03

I I understand the what I wrote uh somewhere sometime in one of my papers is that that the the dentist, the periodontist, the hygienist is not only you know somebody who is a uh is an oral care giver and and performing all the time a procedure, but also is part of a you can say a team of coaches that helps each person in their in their lifestyle, yeah. So we should take up a a bit a piece in lifestyle coaching, and that uh Martin is not so difficult because we see problems in the mouth, so we can say one of the things you can s you can do is stop smoking, yeah, and in the dental field to stop smoking has been really worked out, and there are stop smoking uh techniques and and and also referral addresses for it. So that's one thing, and we can talk about uh their general health, how it affects their oral health, and we can recommend to seek help, for example, for overweight. Yeah. So many things are not so easy, but we should do it.

Martijn Verhulst, PhD 38:21

Yeah. So um so there's actually a bigger role for oral car professionals to uh too.

Prof. Bruno Loos 38:27

And that kind of fits also you mentioned in the very beginning of our uh in this uh discussion uh the holistic care. Um the dental professionals are uh taking care of um the patient and not only of the organ the mouth. We should take care of the patient, and that means there's more behind the mouth itself, it's the whole patient, and the uh the condition of the whole patient affects the the oral cavity. So if we want to get good results of our therapy in oral for the fight of oral diseases, we should think about the other factors that affect the oral health.

Rachel Chau, DDS 39:14

So we have now a better understanding of what immune fitness is. Can you maybe detail a bit more about the mechanism on inflammation with its biomarkers, they're all the most well-established ones so that we can understand better the cascade of inflammation?

Prof. Bruno Loos 39:32

That's a very, very difficult question. Um biomarkers are um in fact markers of inflammation and uh that have been used to you could say characterize the inflammation, but it doesn't mean per se that they are also playing say the pivotal role in the inflammation, it might be a byproduct, so we have to be careful. Biomarkers is just a marker and not per se the true uh um molecule that is part of the pathophysiology pathway in in certain ways. Most of the time it is, but we have to be careful. But anyhow, just a way to recognize inflammation. We use we like to use biomarkers, but today, still the the typical biomarkers as like interleukins and prostaglandins uh are um yeah are important in the whole inflammatory process and can be used as as markers of ongoing uh inflammation. There is for years already the the interest to to say, can we screen for periodontitis using these particular inflammatory markers or biomarkers? So that has been done. Uh but always I I doubt if it is uh some useful tool for for the dental professionals because we have the patient in the chair and we can do quickly an oral examination and see if there are uh if there's inflammation of the gums, bleeding gums, etc. So the screening for periodontitis is more something that could be useful in a physician's office or in a hospital where people are treated for other diseases and where the physician is very uh knowledgeable and understands that also processes in the mouth like periodontitis can contribute to the difficulty of controlling the disease or that it contributes to disease. So physicians may be interested in having a simple screening tool for periodontitis. And there I think if if companies like yourself are interested in developing screening tools, the biomarkers, the immune markers might be the first uh choice.

Rachel Chau, DDS 42:16

If you say it's not really for dentists but more for physicians, then you mean not uh based on uh the the gingival crevicular fluid, for example, rather on blood or on salivary tests?

Prof. Bruno Loos 42:30

I think the the um it is rather difficult to um to take a crevicular fluid, gingival crevicular fluid, and that process of taking gingival crevicular fluid, crevicular fluids, it's a different GCF. GCF that's good is um is something that um you you can easily do use your probe and see the inflammation or bleeding on probing. That is my I can say personal view. I know there are people who say, okay, we have a chair side diagnostic test for periodontitis, but we should be able to diagnose to at least screen quickly and then do an extensive diagnostic procedure. So the screening is more, I think, for outside of the dental office. That's my personal view. And then inside the dental office, it would be nice to screen for, for example, unknown diabetes. Yeah. So the dental office can say focus more on can we help the holistic approach to the patient? Can we screen for diabetes or cardiovascular disease risk? And um, so that is a different thing for the dental office.

Martijn Verhulst, PhD 43:45

You have quite some research on that as well.

Prof. Bruno Loos 43:47

Yeah, we true, because we found that um uh quite some people uh in the periodontal office patients have uh higher risk for cardiovascular disease event in the Next 10 years than people without uh periodontitis. And again, we talked about it before: the diabetes, the prevalence of diabetes is much higher, and also unknown diabetes in the dent in the periodontitis, in the periodontal office, people with periodontitis. But the biomarkers are uh is very interesting, and I'm I'm involved in that uh research. If we can see if there's for physicians or even for home use a set of salivary biomarkers that we can use for screening of periodontitis, diabetes, uh cardiovascular disease, if it's present in the mouth and being uh and we have to find out, we are still in the process if it is really if you can find unique protein signatures or other uh metabolomic signatures or microbiological signatures that correspond to the um to underlying diseases.

Martijn Verhulst, PhD 45:04

I remember you were talking about the fingerprint, the salivary fingerprint. Yeah.

Prof. Bruno Loos 45:08

So that would be because I think uh having one marker is never going to uh help us. It it it must be a set. And today, in in the omics time, uh using proteomics and multiple proteins, uh we're hopefully we can we can find a set fingerprint of proteins that could discriminate patients with and without diabetes or unknown diabetes or their high levels of glucose. Having high levels of glucose, we can measure glucose in saliva. So there are there are things to do that we can measure in the oral cavity. Actually, we are in a very nice position as dental professionals because the mouth is easily accessible as a gateway to the rest of the body without taking blood. Although we haven't found the right uh markers yet.

Rachel Chau, DDS 46:04

But salivary then, right?

Prof. Bruno Loos 46:06

Yeah, so it could be yeah, I can say oral fluids. Let's make it oral fluids. Yeah. So that's a mix of saliva plus ginger fur flicker fluid if you ask people to rinse, for example, have oral rinses.

Rachel Chau, DDS 46:19

I would like to talk now about uh um a trip you made in the US. You said that you spent a decade almost uh in the US uh earlier in your career, but actually beginning of this year, you also spent a mini sabbatical at the Harvard Dental School of Medicine.

Prof. Bruno Loos 46:37

Yeah.

Rachel Chau, DDS 46:38

Why? Why did you go there? What did you do there?

Prof. Bruno Loos 46:41

Yeah, so it was um a good opportunity uh after I don't have much uh not so many responsibilities anymore in the department except for the research and the PhD students. That um a nice opportunity to travel around, and uh I was invited by the dean, uh William Giannobile from Harvard School of Dental Medicine to spend uh a short period of time there. So it was um it was very nice, and uh I thank Sunstar for sponsoring me as well to spend some time there, and uh so I had a what we call indeed mini sabbatical. It was um very nice time to spend some time in the department of uh oral medicine infection and immunity with uh Professor Ferris and also the department of regenerative medicine of uh Dr. Giannobile to um to uh meet people in their labs and to exchange ideas about the research that was uh ongoing. I was invited to um write some um uh review paper, so I thought this is a nice sabbatical, it's a nice moment to find some rest and uh secluded moments to uh to write on this um uh review, so that's what I did.

Salutogenesis: Why do some people stay healthy?

Martijn Verhulst, PhD 48:02

I think uh the one of the papers that we are very interested in is uh because it's a topic you do not really hear that often. I, for example, had never heard of the topic before we uh before we prepared for this podcast, which is the salutogenesis. Yeah. Uh salutogenesis is a term used in the medical field, um, but now you also hear it in the context of periodontology. And um, yeah, as we do not know anything about it, we were curious to hear your thoughts because that's one of the papers you're going to write or are writing following your uh sabbatical.

Prof. Bruno Loos 48:35

Yes, yeah. So um that was um one of the um main things right about salutogenesis, and that's um a term also for me was rather new, but it's it actually is the opposite of pathogenesis. So basically, what we what you look for in biological terminology is to uh to see which factors are inherent or characteristic of a person that makes the person resistant to periodontitis. So, why is the person not developing any periodontal disease? Uh, what salutogenic factors are there inherent to that person? And uh by studying that I followed a little bit my multi-uh causality uh model for periodontitis. I said, okay, now I have five clusters of causal factors for periodontitis. Let's see within those five clusters which factors uh can be found uh that are really protective for periodontitis. Yeah. So uh I looked for genetic factors, and there indeed is literature that shows that certain genetic variants are associated with not developing periodontitis.

Rachel Chau, DDS 50:00

If I paraphrase what you are saying, salutogenesis would be the factors that create health, and pathogenesis would be the factors that create disease?

Prof. Bruno Loos 50:10

Is that it is not create, but are the factors that some person has that makes him more resistant to the to the disease.

Martijn Verhulst, PhD 50:22

So you're approaching a person from a state of health rather than because we're always used to talking about disease, and always when we talk about patients, we talk about disease. But this focuses on the health of the patient and why try to understand why that person is still healthy despite some factors that in other people would cause disease.

Prof. Bruno Loos 50:40

And actually, what I learned, and we uh, because I wrote it together with uh Mark DeFires and Will Giannobile and um Hatis Haturg uh Hasturk from Forsyth Dental Center, also in uh Boston, by focusing on why somebody does not develop the disease actually helps us to to even more uh focus on those factors when they have the disease, and to understand if you can change certain lifestyle factors that may help to become in a higher state of immune fitness, coming back to it again. Yeah, but so we have genetic factors that appear to be in the literature uh yeah, helping a person to be resistant to periodontitis development, but a big uh chunk is the lifestyle factors. People who are not obese, people are having a very good diet, a balanced diet, are low, you can say, on a Western diet and high on Mediterranean diet, intake of olive oil, all that not smoking, um, and and particularly looking at the diet of people who become 90, 100 years old, then uh without any diseases. So there we learn from what lifestyle factors are that help to maintain a normal, balanced immune system that protects against the development of a destructive inflammation, periodontitis is destructive inflammation. And uh also that on itself helps also to be um resistant of developing other diseases, so those people who are lucky not developing any um form of diabetes, other inflammatory diseases also will not have that extra factor to stimulate or to push the progression of gingivitis towards periodontitis. So that is uh a little bit what uh what we did, and also we looked at aspects of the microbiota in the oral cavity because there are also yeah, certain what you can say abiotic, eubiotic uh components of the oral microbiota.

Martijn Verhulst, PhD 53:02

We had a conversation in the last season of Lester Oral Health on primary but also primordial prevention. Yes. And there seems to be a lot of overlap because he's, as you said, uh you know, the there's the the cluster of lifestyle factors that are part of this salutogenesis concept. But I quite like the fact that I mean primordial and primary prevention focuses on those factors mainly, but the concept of salutogenesis goes beyond that because it's not just that cluster, but you also have oral hygiene and you also have genetics, yeah. It's a whole um set of factors that keep a patient healthy. Yeah, and I that emphasizes sort of the holistic approach that we have. We're not just cleaning mouths, but if you take into consideration the lifestyle and the genetic background and the development the person goes through through life, you have a much better picture of why this person develops disease or stays healthy.

Prof. Bruno Loos 53:55

Yeah, people some people are more lucky having the right genes, for example, and also you can say the uh resources to consider their their own health and be in charge of their own health, uh that helps. Yeah, that helps. So, in a regular dental practice, many people do not have yet periodontitis, but um it could be they develop in in some time, they may develop periodontitis. But if you are aware as a dental professional that there are factors that make the patient more resistant, so then you can always say, uh, I see some gingivitis that can derail at some point to periodontitis. But if you can uh maintain a certain lifestyle and uh stay healthy and realize that you should not smoke, but also think about if you develop any disease that you take care of it, yeah, then all in all your your you can say your immune fitness and your total strength is increased, and you may also protect yourself against the development of periodontitis.

Martijn Verhulst, PhD 55:09

Little side quest, maybe um that's just a thought that now pops in my head. But do you think there's also uh that this concept of solitogenesis is maybe also what underlies these what we call blue zones in the world? You know, you have these little zones in the in the world where without a really clear explanation people get a lot older than the area directly around it.

Prof. Bruno Loos 55:29

Yeah, uh so the but that could be genetic, yeah, because people in in certain areas may have marriages, right? So that's a possibility, yeah. Uh but also the the type of diet they have and their culture. Exactly. So in the salutogenesis paper, it became a massive paper. We we also talk about cultural differences, right? Yeah. And uh the concept of salutogenesis, maybe that's also actually came from um survivors of holocaust uh experiences where it was seen that certain uh survivors um although have suffered from major life-threatening conditions could uh cope with that, yeah, could deal with that and and could stay healthy while other people may suffer from post-traumatic stress, uh etc. And um that is where the concept initially was um was studied and brought forward. Old age in a rather healthy situation, uh even though they had these uh Holocaust experiences, and um so it's not only it's not only, and that is also for our period of field interesting the lifestyle in terms of diet and and and the genetics, but it's also um mind over matter. It's that uh how you can cope and deal with certain lifestyle life stressors, I mean. So we we have to keep that in mind. That was interesting, uh, another aspect. We haven't mentioned much stress, but that is another aspect we have to uh reduce your immune feature.

Martijn Verhulst, PhD 57:21

It seems to be a big uh psychological uh aspect as well.

Rachel Chau, DDS 57:25

Body, mouth and mind actually also take into account.

Prof. Bruno Loos 57:28

Yeah, yeah, yeah. But uh I think an a very important um take-home message of our discussion today is that uh we have to realize the diseases, the chronic diseases we are working with periodontitis, others were cardiovascular disease with diabetes. Uh these are multi-causal diseases. So it's never only stress or only bacteria or only genetics. It's always a combination of things that make somebody eventually susceptible for the disease. Yeah. Yeah.

The Future: AI & Predictive Dental Medicine

Rachel Chau, DDS 58:05

But before we wrap up, um I would you said that uh the paper on salutogenesis is becoming massive. But apparently your your sabbatical to uh Harvard School of Dental Medicine was very productive because you have another paper uh where you talk about the past, the present, and the future of periodontology. And it would be nice, I think, for before we wrap up to um to see what you think of the evolution of the pure dental medicine. Looking ahead, what do you see uh in the future?

Martijn Verhulst, PhD 58:36

Is it massive as well? The paper?

Prof. Bruno Loos 58:38

Uh no, no, no, no. It's going to be a very short paper. Okay. It's uh it's more what we call perspective. But uh yeah, the future it the obviously it's very difficult to um to foresee what happens in the in the near future, and we are always kind of uh using the current times the uh the uh as to um um extrapolate from the current times to the uh to the future, and um but the the the further future is is very difficult, but I foresee enormous uh use of the artificial intelligence. That is what I think happens. I'm very fascinated by the possibilities. Artificial intelligence particularly is designed to predict. So if we talk about a chair side test at some point, uh we don't need the biological chair side test anymore. There will be other, we can say, tools where there is absolutely none uh not invasive and not using the mouth itself but rather using questionnaires or uh medical histories, dental histories to predict if somebody might develop uh periodontitis. And um I'm helping a student on an AI model using dental records to predict if somebody may develop periodontitis. And uh recently a nice or large paper came out that uses medical records to predict more than a thousand diseases in the next four years, five years, ten years. So that might be the direction that we may also go into if you think about periodontal medicine and the relationship between the mouth and the overall health. So dental professionals at some point, or maybe not even in the dental office, but you can give certain type at a certain moment you can give certain questionnaires and with algorithms behind it, uh can say you have a higher risk. It's everything is probability, yeah? So you may have a higher risk or higher probability to develop diabetes, to develop cardiovascular disease. And the dental office is quite a nice place because we talked about it, we see patients every year or twice a year. So you can monitor and redo those questions. Patients go more often to a medical office if there's a true problem. So if you can use future artificial intelligence tools to predict, that would be very nice. So that would be uh uh some sort of a utopia for me. Yeah, and uh I would also would love that the future is that um dental offices or periodontal offices, let's keep it sure as simple, is that they combine all the records and that you get a good data set to uh develop uh um AI algorithms for predicting diseases and periodontitis and the progression of the disease, periodontitis. That's yours and also predict who needs more interdental uh brushes and and more attention for that. That would be very useful.

Rachel Chau, DDS 1:02:13

Yeah, yeah. Interesting times uh lie ahead.

Martijn Verhulst, PhD 1:02:16

Yeah, and that's the that's your views on the future of periodontal medicine. Um you mentioned the PhD student already. Um what's in it for you in the in the near future? Um, you said already, um, being an emeritus professor, stepping down a little bit from from teaching, and and of course treating patients as well. Um you're focusing now on your PhD students. Um is there some nice projects going on? I suppose so. What the what is the what is it what is ahead of you in the in the coming years wrapping up those uh those uh research projects?

Prof. Bruno Loos 1:02:46

It will come naturally, I think. Um but I'm very interested in in um how periodontal medicine and and the whole field of periodontology develops itself, and uh I would like to stay active in it. Yeah and um I will collaborate and uh help young colleagues to uh to to do their research. That's uh that's my um goal in life and also my pleasure in life.

Rachel Chau, DDS 1:03:14

I think we have come to an end of our conversation. So thank you very much, uh Bruno, for sharing all this deep, insightful uh information with us and with our audience. It's really been uh an honor to have uh to have you with us.

Prof. Bruno Loos 1:03:30

Thank you very much. Well, thank you, Rachel and Martin. Thank you very much. And uh it was my pleasure as well and my honor to be here. And uh I would like to congratulate you and your company also with your um yeah, with your uh mission and vision on on oral health and general health. How you uh work on that topic is uh very nice. Congratulations. Thank you. Thank you. Thank you.

Rachel Chau, DDS 1:03:57

We'll continue in that direction then. Good.

Prof. Bruno Loos 1:03:59

Excellent.

Rachel Chau, DDS 1:04:01

Thank you all very much for tuning in. Well, I hope that you enjoyed the conversation and that you took some advice for your daily practice. Marta and I will be happy to see you again at our next episode with a new conversation and a new guest. See you soon.