Dr Jelena Vulevic on Delaying Ageing using Prebiotics and Postbiotics

This episode is brought to you by Nourish Me Organics, your gut health superstore. Nourish Me Organics is the premier online store for all things gut health, including probiotics, prebiotics, natural health supplements and home fermentation kits. So head to www.nourishmeorganics.com and use the code happygut for 10% off. Join Kruban Govinda, a seasoned food scientist and GU health expert. In this episode we chat with Dr. Yelena Vulovic on delaying aging using prebiotics and postbiotics.

Hey guys, C gave from the Gut Health Gurus podcast. I've got a background in food science and today I have an amazing guest. I've been wanting to speak to this wonderful lady for such a long time and finally the stars have aligned and we're having this conversation. Long awaited conversation. Yelena vc, welcome to the show.

Thank you, Criben. It's a pleasure to be here. It is true it's been over over a year. I think that we've been trying to arrange this date. So yeah, I'm happy to be here.

Thank you so much. And what I'd like to to get at the start of the show, Yelena is is straight from the horse's mouth, who is Jelena Vulovic.

So I'm first of all I'm a mother. I think that's the most important job in my life. But I'm a gut microbiologist. That's what I did my PhD in. I spent 12 years doing academic research and then I transitioned into industry working for about eight or nine years. And then four and a half years ago I decided to join in with my long term work partner, George Georges and we formed a company called Vermico. So that's really the shortest introduction of who I am.

Great. What a way to start the show. I'm just going to throw a little bit of a curveball at you. When I say the word Nikola Tesla, what does that mean to you?

It means it's a name I've heard since I was a kid. I was born in the country that used to be called Yugoslavia in Sarajevo. So I'm Bosnian and I came to the to London in UK in 1992 as a result of the war there. So Nikola Tesla, obviously being born in the same country where I was, was a big name when I was growing up and a name I heard from my grandparents and then throughout the school. And I hope everybody in the world has heard that name because he's an important guy, not just because of the car that Elon Musk invented, but of many other things that he's done.

Yes, certainly Nikola Tesla is a, an immense inspiration for myself and the amazing work that he's done. So hopefully, as scientists we can be somewhat in a fraction of the shoes that Nicola wore. And Elena, I think I've been following your work on LinkedIn for some time. That's how we particularly met. But you, you've been involved in quite a few studies when it comes to the gut microbiome. And I'd like to start the show off because I think many people struggle with some sort of connection between the gut microbiome and the immune system. So how does the gut microbiome influence our immune system?

First of all, I'd like to say the difference between the microbiome and the microbiota because I find it a little bit annoying when I read things. The microbiome is the collection of genes of the microbiota, which are living organisms present in this case in our gut, but not only in our gut, literally everywhere, on and around us. The microbiota, which is probably the term I'll use most of all because that's what refers to the guys that are living and there is really not only influential when it comes to the immune system, but also they are the main guys that manage the immune system throughout our lives. So when we're born, we don't have the immune system. We get what we need from mother's milk, if we're lucky and we're breastfed, we get lots of things from the environment. And of course today all the new formulas will try and introduce as many things as possible to help that immune system and help the protection. So especially during those 40 days of life when we don't have the immune system, it's the microbiota which is inside our guts that's really driving the protection mainly of the infant against everything that can go wrong. And then, so that's where it all starts. And then throughout the life, the microbiota manages and is constantly involved and interacts with the immune system in a good and in a bad way, which depends obviously on our microbiota makeup, but then on everything else, you know, who we are, where we are, what we eat and so on. So the connection between the two is very strong and very real. And they cannot really be split into two. Even though they are two different entities, they constantly interact.

Right. And very early in your, your journey you did some work with ulcerative colitis. Now a lot of people struggle with ulcerative Colitis. So firstly, how about we define the term and then what are your key takeaways and findings from the work that you've done on ulcerative colitis?

So ulcerative colitis is actually the reason why I decided to study microbiota. Because in the last century, in 1995, when I was a student, well, I read some works from Hippocrates, but then that led me towards few other things. And then I found studies from a Japanese group whose name I can't remember now, I do apologize to them, from 1980s, beginning of 1980s, where they looked at certain components from the microbiota, and these specific components could be involved in colorectal carcinogenesis. But first of all, through the initiating some inflammatory responses that are resembling ulcerative colitis. So ulcerative colitis is an inflammatory bowel condition, one of the two. The other one is Crohn's. And the only difference, well, not the only difference, but the main difference between them is the location. And it's a lifelong disease. We don't have any treatment really. So the treatments are always just the management of symptoms which are related to standard things like GI symptoms, maybe pain, bloating and so on, but also bloody diarrhea. It's not good to have it. And there's a very. It isn't really known what starts the ulcerative or how it starts the ulcerative colitis, but there's a very strong link between the genetics. So you do need to be genetically predispositioned between the inappropriate response of the immune system and inappropriate microbiota makeup. Now, whether the microbiota reacts to whatever happens within the body in terms of the immune system, and is there therefore not so good, or it's the other way around, is the question I've had for almost 30 years and I'm still unable to answer. And that's not just the case with the ulcerative colitis, but very many things, though I have changed my mind about the microbiota from where I was 30 or 20 years ago to where I am today and how I see it within the human body.

You mentioned the difference between these two conditions being the location. So how about we delve a little bit deeper into the locations of those two diseases?

So the ulcerative colitis always starts at the rectal region, and it extends distally from the rectum upwards into the colon, whereas Crohn's disease could really appear anywhere within the gastrointestinal tract. And it can be patchy. It doesn't have to be all in a continuous, affecting a continuous region of the gut, but you can get it all over, even in your mouth. So that makes treatment of Crohn's disease somewhat more difficult than ulcerative colitis, but they're equally difficult to treat and to manage symptoms.

And what options do people have in terms of alleviating some of those, the symptoms associated with those diseases?

There are some standard medical treatments, though I'm always on the side of the lifestyle, a modification of the lifestyle that includes diet, obviously, so removing. Because a lot of people who have ulcerative colitis or any form really of gastrointestinal disorder will be or will eventually become, as a result of their condition, intolerant to various environmental pollutants, factors, including dietary components. So removal of those, recognition of those, and then removal of them is always a good way forward. Things that obviously modulate the microbiota, because microbiota, even though we don't know which way the road is going, is influential. There's plenty of evidence out there that not only the symptoms, the GI symptoms, but also the inflammation and the amount of inflammation that enters the body and more importantly, the intestinal barrier, which is really the key, in my opinion today, as opposed to what I thought 20 years ago, can be influenced heavily and is actually influenced only by the microbiota. So a lot of things like prebiotics and probiotics and postbiotics today are things that people need to try. The only issue there is that there are so many things out there in the market and we are all so different. So very often, often, as it is the case with any condition, there would have to be a lot of trial and error trying things and then finding out what works for you. And I really have to say something here that, you know, we live in a world where everybody expects things to happen yesterday. Well, when you deal with the gut, such a dynamic and a huge environment, it is impossible really to expect things to happen overnight. So I always tell people that when you start something, give it at least a month, but ideally three months if you want to deal with huge things such as inflammation before you make a decision, oh, well, this is good for me. Or not. Obviously, from the beginning, let's say after the. During the first week, most people can experience symptoms that aren't very good, but if they continue into week two or three and they really troublesome, then of course, I mean, that's not the product for you. But to decide it's good or not, you've got to give it more than just A few days or even few weeks.

That's so true, Yelena, because it takes, and imagine it takes some time to develop these problems, perhaps even a lifetime of poor choices, and then we have this expectation that we're going to solve the problem by taking a pill or some sort of intervention. But I completely agree with you. That is so true. I have so many questions. The first obvious question is you mentioned that these dysfunctions are a combination of genetic factors, but also certain microbiota. Is there a particular signature of organisms that you found in your studies that could be used as perhaps a marker in future?

So if you asked me that question 10 years ago, I would have told you, yes, there are certain markers, and it is still true. There are certain markers. And in the last, especially in the last 10 years, so much work has been done with microbiota and the microbiome. So of course there are a lot of things we can take out of there. However, where I stand firmly today, based on my work and my experience, is that it is impossible to define healthy microbiota. So what comprises healthy microbiota? Is a basic question that I've spent so many years, and how many people spend so many years, and we still can't answer that basic question, what comprises healthy microbiota? Because microbiota is influenced by so many different things, is the human who's also influenced by all those different things, and then the interaction of the two that is oh, so complex. So until we can answer that question, what comprises healthy microbiota? All the biomarkers that we currently have are useful and in some cases are not only useful, but we can rely on them. But to apply that knowledge to a population level or to every single person that's suffering with any kind of disorder or a disease is very, very difficult because we've seen, I'm sure you've read, I've seen it in my own hands, taking people who on paper look identical in terms of their genetics and their background, their diet, lifestyle and so on, and yet they have completely different microbiota. I have worked with people with ulcerative colitis whom I followed for a year, and I took their samples, their stool samples, and analyzed their microbiota every month over a year. And during that one year, even in that same person where everything was controlled, including the treatment and the diet and everything else, they had very, very different microbiota makeup. So I would have to say that, you know, it's a difficult question to answer and I wouldn't be able to tell you, well, X, Y, z, is good. However, we do know that certain members of the microbiota are beneficial. So you want to try and increase those with the diet and lifestyle and additional functional food ingredients. And then we also know that certain lifestyle and certain components of the diet are bad. So obviously you want to keep those down, such as, you know, high fat diet or eating too much meat or not exercising or smoking or drinking too much and so on. But I think most people probably know that without needing an expert.

That's an amazing insight coming from such a, such a key researcher in the field. And you know, it's very humbling to, to, to make that statement that we, we don't know enough yet. But it's, it is a, it's still a nascent field. I mean it's been around for a while, but it's still a nascent field. And it will take some time, I think, to peel back some of the layers and get more insights into how these body genetics, our microbiota react and how we can solve some of these problems in future. So I think there's. Sorry, keep going.

If, if I can interrupt there. I do think, because I was some five years ago when I came to this realization, I asked my question, I asked myself a question. Okay, so what do I do? I've spent all these years trying to modulate the microbiota, looking for the healthy looking microbiota in order to exert a benefit onto a human. And now I've come to this realization that I'm never going to answer that question. So what do I do? I give up and do something else or what do I do? There is an option and I do think one day we will answer that question. It's just that day is not today and I don't think it will be in the near future. However, there is a lot that we can do because microbiota is influential, we know a lot about it. So the thing that we can do and the thing that I've decided to do with George is to extract the benefit from the microbiota and bypass the need to change it. Bypass the need to even. I don't want to change, I don't want to say bypass the need to change the lifestyle because we should all try to have a balanced lifestyle, but at least help a little bit that need where if you're going and trying to modify the microbiota, you don't really have to change your lifestyle as well in order to get the real benefit. So bypass the need of all of that. Not worry so much about the Microbiota, but concentrate on the human, concentrate on the tolerance, because it's very simple. It doesn't really matter what's microbiotic. It doesn't matter what's the environment. If us humans in our immune system can tolerate whatever comes our way. So if we can increase that tolerance, then we can manage a lot more than we're able to do if our tolerance level is down. And we can do that by extracting the beneficial compounds from the microbiota that we know and have been around for a long time, time, and bringing them back into the human body without the need to interact with the microbiota. And I think that's the way forward. That's what postbiotics are, and that's where we decided to concentrate on. And I do believe that's the new frontier in gut health. And I don't want to say the only one. It's not the only one, because all the others obviously have their space and an important one, but it is the new one, the one that could bring the whole of gut health together and not just one component, which is microbiota.

I'm so pleased that you brought that up, Yelena, because it is absolutely on point with the way my thinking is in this current, this current time, place in time. I think it's really about the metabolites that these microbiota produce. And then in your work, trying to replicate some of these metabolites and then using them as a. Almost a personalized nutrition tool. So, firstly, I think the audience might not be familiar with a postbiotic. Certainly, I think probiotics and prebiotics have become very trendy, so people get that. But what is a postbiotic?

There are few definitions, and there's some controversy with those definitions depending on where you look. But put in simple words, a postbiotic is what a probiotic produces when they eat a prebiotic or any other food. So it's beneficial compounds that probiotics produce, and those are produced daily in our guts. They're also produced in fermented foods like yogurt or kimchi and all the rest. So that's really what postbiotic is. It's the metabolites or the end products or however you want to call them. Now, some definitions say that postbiotic must also contain dead components of bacteria or other microorganisms. But I think that's. That's going into real scientific details and maybe not that important.

I love that simple definition. I think it serves the word postbiotic very well. People might be familiar with things like butyrate but one that is certainly an expert on is a compound called Beta Gauss. So how about we jump into that rabbit hole and explore beta costs a little bit more. So firstly, what is Beta Gauss and how is it made and what are the benefits? There's a lot of questions there, so we can go slow.

Okay, so B Gos, or Beta Gauss, as you say, which is correct, is actually a prebiotic. It's not a postbiotic. So it's a prebiotic. There are lots of prebiotics on the market. Not just on the market. There are lots of prebiotics in foods. The beta galactoligosaccharides, that's the short or the longer version of GoS, in my opinion. I have spent a lot of time working with all sorts of prebiotics, natural, synthetic, and however you want to call them, beta gases, which naturally don't really occur in anything other than breast milk, human breast milk we're talking about here. And even then, they structurally resemble some components of human breast milk, oligosaccharides, which are extremely complex and change throughout the day, even throughout the feed of the baby. So they are the closest, structurally closest to human milk oligosaccharides. So they are the best immunomodulatory prebiotics that you can have because of what they do in human breast milk. Now, as opposed to fructoligosaccharides, for example, which or faucets, which most people are probably familiar with, that are one single structure. Galact oligosaccharides are a mixture of varying oligosaccharides of varying length and also chemical structure. This chemical structure that they have depends on the origin of the enzyme. So from which bacterium they are produced, that is a key in their functionality, meaning how they're going to behave when they arrive into your gut and how they're going to interact with not only microbiota, because all prebiotics or well designed prebiotics will support beneficial components of the microbiota, influence the diversity and all that. All prebiotics will do that. But these specific prebiotics or certain components of their structure will also interact directly with immune cells. And that interaction will depend on the chemical structure, and chemical structure depends on the origin of the enzyme. So most commercial gases come from one strain of bacilli, which is all right as a prebiotic. But a better idea is to take actually enzymes from a probiotic such as Bifidobacterium. Lots of people have heard of it, we have plenty of evidence out there that These guys are good because we then not only select for their growth and increases their increase in your own gut, but we also then bring about a lot of other benefits that those bacteria have early on and their interaction with the immune system. System. So we've worked previously with gases, and I just have to add something here because a lot of people call galactoligosaccharides things that come from soya beans, for example, but those are not galact oligosaccharides I'm talking about because soya beans, galact oligosaccharides are actually something very, very different structurally. So we've worked previously with galact oligosaccharide bimuno, and this time we have developed a different one which is also from Bifidobacterium, but from Bifidobacterium breve, because bimuno is from Bifidobacterium that's dominant in infants. And this time we have chosen the bacterium that's dominant in adults that gives it a little bit more, a lot more, I would say, benefit when it comes to adult population and its interaction with the immune system. So those are prebiotics, very special prebiotics, probably, or in my opinion, the best ones in the market. If that's what you're after and you want a prebiotic, go for trans galact oligosaccharides or beta gases.

In what situation would someone consider using a beta gauss?

Using Big Os? Yeah, so you could, if you, if you're. Look, we all, none of us have a perfect lifestyle. I've never met a person who has a perfect lifestyle. So I think everyone should take some form of a functional food ingredient which does not necessarily have to be beat a gossip. But then people who suffer with gastrointestinal disorders such as ibs, for example, would benefit from. For anybody who wants to improve their, their own probiotics give them a bit of a kick in the gut. It is a substrate to take.

Great. The, the connection just dropped off a little bit there. So perhaps you could repeat that. What, what is the benefits of beta gauss? I think the last point you made was around something around the immune system, but I think we better repeat that section.

So the beta gases, well, for anyone can use them, as I said, anyone who wants to support a little bit more their lifestyle and support their own probiotics that are already in their gut and give them a little bit more kick when it comes to the immune system. But more specifically, people who suffer with gastrointestinal disorders such as ibs or want to treat similar symptoms. So ulcerative colitis is one of them could also benefit from beta gases. But we do have an upgraded product which is a postbiotic. And that's something else that is a real postbiotic, not just prebiotic compounds that actually interact with us humans and not the microbiome. The thing I said earlier in our chat.

Elena, the burning question after that previous information about GOS is what do you think are the key benefits of beta Gauss?

So it's a prebiotic and it is in my opinion the best prebiotic out there because of all the things I've said. So it's the best thing to take if you want to support your own good guys. So your own probiotics that are already inside your body and have been there for a while and know how to deal with you and your environment, lifestyle and everything else. So it gives your microbiota a bit of a kick because it gives the ability to those good guys to thrive and flourish in your own environment. And that obviously has a lot of different benefits coming from the microbiota. It improves diversity, which we all know is very important when it comes to microbiota. But in addition to that, they also certain components of those beta galact oligosaccharides will directly interact with the receptors and the immune cells down the gastrointestinal lining. So it gives an additional benefit which most or nearly all other prebiotics cannot do. Because prebiotics are mainly there to feed the bacteria, they are food for microbiota. I don't want to say just bacteria, but galact oligosaccharides have that additional benefit that they can interact directly with the immune cells to, to an extent anyway.

Is any particular organisms in the gut that helped by beta galactose? Is there certain species or strains that the bigos helps to boost up?

The beta galactosidase is the enzyme required to deal with those. So there are a lot of different organisms that have them, but the main group that we really want to support are bifidobacteria. They are the guys. So the beta gases really target mainly bifidobacteria, but not only. And of course this is going to have a knock on effect on other bacteria, but that's their main job to support the growth and increase the numbers and metabolic activity of bifidobacteria in the gastrointestinal personal tract.

People, people often anecdotally mention benefits of God, something like sleep, stress, mental health. So a broad question is, is how. How is the Gut and the brain connected. And how could goss be benefiting in this regard?

Well, the gut and brain are connected through this vagus nerve, as we know. So the gut produces a lot of compounds, including the neurotransmitters, etc. That are then transported via the blood barrier and interact with the brain. Nearly all microbiota in the gut will, or I don't want to say nearly all, actually all, every component of the microbiota or every member of the microbiota will produce something that can interact not just with the brain, but with every organ in the body through the interaction with other members of the microbiota, but also mainly through the interaction with the immune system, because of course the immune system is also influential in the response of the brain. So that's, that's how they are connected. They are connected through this vagus nerve. And now the microbiota produces a lot of compounds that are beneficial and in this case bifidobacteria. And I don't think it's, I don't think it's right to say that only bifidobacteria or lactobacilli produce those beneficial compounds. But what's right to say is that our knowledge today sits on something like that. That's where we have the most knowledge. So I am a firm believe believer that when it comes to, when it comes just to pure science, academic work, then we can talk about lots of things. But when it comes to maybe giving an advice or giving something practical people can use and incorporate into daily lives, then we should really stay within the field where we have the most evidence. And today that's where we have the most evidence. So these guys are known to produce a variety of different compounds, including the neurotransmitters, they influence the hormones, etc, and that's how they are connected to the brain. And not only brain, but also the endocrine function, which is extremely important within the human body.

Yelena, that's a perfect segue to go into a particular study that you were involved in around Bifidobacterium brevi BB091109, around the inflammatory status and endocrine function of a postbiotic derived from this particular bacteria. Are you able to provide more information about this study and some of your key findings?

I need to just take a step back and you may not be able to include all of this in the actual podcast, but never mind. I want to start with what is gut health before we lead onto that study. So gut health to a lot of people is all about microbiota. Gut health to me is not just microbiota. It's all the things like digestion, absorption, absence of illness and so on. But the key to achieving gut health are two entities. One is microbiota and one is barrier, intestinal barrier function. So the good gut health depends on the interaction, on the not on interaction. It depends on this intact gastrointestinal barrier and the fine tuned communication between the microbiota and the immune system. I think I touched upon this barrier function earlier and I'm just gonna say it again. So the, the barrier function or this almost the mechanical barrier that's between the human and its outside environment, and the microbiota sits on the outside almost even though it's inside our gut, is crucial for literally everything that's going on in the body. Because if this barrier is intact and healthy, then almost, it doesn't matter what goes on on the outside. But when the barrier is not doing so well, that's when the problems start within the gut. So locally, but also systemically in the brain or in the. Well, in any organ in the body, including the endocrine function. So why is this important? Well, it's important because of the inflammation. The low grade inflammation, as we know today, underpins literally everything that can go wrong in our body. From the wrinkles on our skin to Alzheimer's and type 2 diabetes and anything, any chronic condition. The only things excluded are infections and obviously genetic disorders. So this buildup of the chronic low grade inflammation comes from the environment, and the environment in this case is our lifestyle, diet and the microbiota that processes all of those components. So the microbiota drives the amount of inflammatory compounds that enter our body. And this gastrointestinal barrier is there to either prevent or let the entry of those compounds. So the inflammation, the low grade inflammation, it builds up, it's a natural process that builds up in our body because that's what is causing aging. Eventually when we have too much of this low grade inflammation, which we cannot avoid, I mean that's what happens. We're human, we have expiry date and I think we should have an expiry date. I don't think humans should live forever because look what we've done with the planet. But that's another topic. So as this low grade inflammation accumulates, accumulates, eventually it gets to the point where we can't tolerate it anymore, where this barrier becomes porous and it becomes unable to deal with it. And that's where we really notice the effect of aging. So this Inflammation, low grade inflammation is important. The barrier is extremely important. And in fact, the most important thing is how much we can tolerate. If we can tolerate a lot, we can stay young. By young, in this case, I mean healthy for longer and we can deal with things. If we can't tolerate it, or we have really quite inappropriate and terrible lifestyle and diet and so on, well, then we're gonna get sick very quickly. And I think that's what we're seeing today. We're living way longer than we did 20 or 50 or how many years ago. But actually most people spend a lot of those years being sick, ill, or requiring some sort of a treatment. So I've forgotten now what was the main question with my introduction? The postbiotic.

The postbiotic, yes.

So knowing that the microbiota is influential when it comes to interaction with the immune system and the keeping this barrier intact, and that the microbiota produces a variety of compounds, including the compounds that can prevent the buildup of this inflammation or the translocation of the inflammatory compounds into the blood and into the human body, which I just hopefully explained is very important. We've decided to concentrate on those specific compounds. So we've decided to extract those specific compounds from one specific strain of bifidobacteria. And maybe not so important, I mean, if it is, you can ask me, why have we chosen that strain? But we've decided to extract those compounds. They are exopolysaccharides, so they are types of sugars, let's call them like that, for the simplest explanation that these bacteria produce, as indeed many other bacteria produce. And they have very, very specific function because they, they act as TLR4 agonists. If I'm going too, too technical here, please tell me, but basically the lining of the human gut with the majority of the immune system is, has all these different receptors which are like keyholes. And then the bacteria have all these different compounds that they produce. And these compounds, if they are the right ones, can either open or close or whatever the door. And these keys that the bacteria hold depend their function and their functionality and how well they can interact with the immune system depend on their chemistry. So we've chosen to extract these specific compounds that can affect a specific part of the immune system. And in this case what they do is they block the receptors down the gut lining. And by doing that, they reduce the amount of inflammatory compounds that enter the body. So in a way what they're doing is they're fooling the immune system that everything is fine. Don't Worry about what's going on on the outside. There's no need for you to go into the overload and work too much and spend too much, you know, you are fine, everything is balanced. And that's what this specific postbiotic is from Bifidobacterium breve. Knowing that it affects inflammation or actually it reduces the amount of inflammation. We also knew or hypothesized that it's going to have an overall or a systemic effect, even though it does not enter the body, on the amount of inflammatory compounds and also hormones, specifically in females, because. For example, cortisol, which is not specific to hormone to females. Sorry, but cortisol is a stress hormone and I think most people know that when we're stressed, this is when we increase the inflammation in the body. This is not good. Too much stress is not good for anyone. I think that's probably well known. But what it does, the stress increases this low grade inflammation in the body. So cortisol is one of the hormones that can be affected. And reduction of stress has many, very many effects on the brain and the rest of the body. But another interesting thing is that with females and me being dhim, I had to concentrate a little bit on that. When we go through the perimenopause and enter menopause, what happens is that sex hormones, namely estrogens and progesterone, drop. And interestingly at that same time, what happens in the female body is that we become more prone to inflammatory conditions. And what happens then is actually that the barrier, the barrier function that I keep mentioning all the time becomes more porous, more inflammatory compounds are let through. So it seems that the estrogen in a female body or the sex hormones in the female body at least regulate the amount of inflammatory compounds that enter the female body. So taking all of this into consideration, we've decided to test this specific product in a female population. Age I think was 40 to 55. So those would have been of the age that are going through perimenopause or maybe have entered menopause. We haven't really asked them those kinds of questions and see the effect on well known inflammatory markers such as cytokines and the C reactive protein. For example, cortisol being an important hormone related to stress. And then of course the sex hormones, estrogens, progesterone. We also looked at the human growth hormone and the dhea which controls the amount of sex hormones. And our hypothesis was that if we can line that if we can prevent, if with our substrate, this postbiotic, we can kind of block those receptors and therefore reduce the amount of inflammatory compounds that are coming from the diet, lifestyle and everything we're doing in this life. We should be able to also reduce in blood and in saliva the inflammatory compounds and the cortisol and at the same time in this female population increase the sex hormones that would naturally be dropping at this age. And that's exactly what happened in this study. We have seen significant effects on all of those that I've just mentioned, or most of them anyway, the most important ones. And we have seen that in fact increase over the three month period that we have tested. We have seen it increased over time, but also against the placebo. And we have also seen interestingly a positive effect in some of those four weeks after we stopped the intervention. And I think that's probably in my mind that's always nice because for a lot of those compounds, for a lot of food ingredients or the microbiota modulators, once you stop taking it, you very quickly go back to where you started. And I think one of the reasons for that is the thing I mentioned somewhere at the beginning, the difficulty in modulating the microbiota and the advantage of this approach where you're bypassing that and interacting directly with the immune system, is that you can have more of a benefit and a more of a lasting benefit in the body. Hope I answered that question.

Oh, that was brilliant. And it's incredibly fascinating to hear the outcomes of this study and the profound impact that it had on that particular female cohort that you chose. Just, just a burning question. Why, why do you think that the, what's the mechanism behind you could theorize on this? What's the mechanism, mechanism of action behind why the benefits endured? Because it was a postbiotic, so it's a certain chemical compound that's been ingested. But why does the benefits endure?

Because what happens is the, the, the thing I, I said earlier is that, you know, we're born and then we start our descent towards death. And during, during. Well, we kind of, we don't go like this, you know, we kind of go like this, isn't it? Because we, we have the child great and adolescence, and then things start going down the hill. And so during that period, what happens and how fast we go down that line depends on how much of that low grade inflammation we accumulate. And actually that has an effect on our immune system and how. Well, our immune system, which I do believe is the key really in the human body, in addition to the microbiota, which is outside, but the key to Everything that goes on and how well we perform and everything else is the immune system. So if you have something that can take away a little bit of that or improve a little bit of that tolerance, give a little bit of a break, let's call it like that, to that immune system, then that effect should, in theory, and I'm only here, you know, this isn't proven, or maybe it is, but I don't know. It's certainly not something we've looked at. But this is just me thinking out loud because it would make sense to me and knowing how it does work, that, you know, if you give a bit of a break, it's like if you. If you do a lot of running or something, and then, you know, you give yourself a little bit of break, the chances are that the next day you're going to perform better than if you just go out there every day and run. Maybe not the best analogy, but that's where I'm leading. I think what it's doing is it's giving it a bit of a break from daily dealing with all those inflammatory compounds. And so the immune system can therefore perform a little bit better after a given period of time. But don't take my word on it. It's just an idea.

That's an amazing idea, Yelena. It's almost like there's a buildup of this chronic inflammation, and then the postbiotic potentially manages to clear some of the information away, allowing the immune system to function more optimally, resulting in an enduring benefit. So that's. That's amazing. And I have to ask you, why did you choose that particular strain?

So we were set on finding a strain of bifidobacteria because of, as I said earlier, there's a lot of knowledge around those guys. And both George and I have worked with those bacteria extensively over the last 25, how many years. So it made sense to concentrate on them since we knew them quite well. So we were always going to choose bifidobacteria. And then we wanted to, because we really. Where we're going with this whole concept and where the company that we started, this healthy aging, this thing that I started mentioned, so not living forever, God forbid, but matching the lifespan with the health span, living healthy for as long as we can. And so we then wanted to work with bifidobacteria that come from a healthy human who's also old, all their healthy human. And so a lot of different strains of the bacteria were extracted from our donor that we have chosen on a lot of different things, but mainly they had to be healthy and old. And then they were tested for their ability to produce different exopolysaccharides. And we have looked at these different exopolysaccharides and their ability to interact with different immune cells and so on. And this particular strain, Bifidobacter bread performed the best and so that's why it was chosen.

Wow, that's an incredible insight into the process of, of how you selected this particular organism from a, a healthy donor. Amazing, incredible, incredible insight. And I'd be remiss if, if I didn't ask you about the connection between the gut and skin because you, you seem to be one of, one of the, a very knowledgeable experts in this area. And, and firstly, is there a connection between bifidobacteria brevum brevi B9BB091109 and your Y skin? So we can talk about why skin a little bit, but is there a connection between the two?

Yes. Well, that's that ingredient, the VMK223 or the postbiotic that's in the paper is actually the Y skin. It's exactly the same capsule that is in the commercial product in Y skin that was tested in that study. So, but, but you see most people, you know, and I said this before, you know, there's one thing doing science, there's completely another offering that product to a consumer onto a market. So we believe, and just if you can remember some of the things I said, this low grade inflammation, the results we have shown the fact that there is a delayed benefit of it and what it all means is that it delays in a way. Aging does not stop it, it does not make you look 10 or 20, I don't know how many years younger. If that's what you want, I think you need to have plastic surgery or whatever is in the offer today. But it delays that aging effect. And when I say aging here it's I mean making you sick, making you unable to move, making you unable to or not unable, but less able to think, and so on. So that is what that VMK223 does and that is what the results from that study are showing. It is delaying that aging effect in this case on a female body, but it does in the male body as well. We just for the purpose of the study had to choose just one. Now how is that connected to the skin? So the skin is the mirror of health basically. And whatever goes on, whatever wrong goes on inside the body eventually is going to show on the skin. There's a very, very strong connection between the gut and the skin through this gut skin axis, same as there is between gut in the brain and gut in the heart and metabolism and so on. And these compounds that are produced in the gut will eventually get to the skin how? Through the interaction with the immune system. So it is not a topic. Or hydration or something like that that comes from the outside. It is pushing that benefit and the balanced immune system, the reduction of those inflammatory compounds overall in the body from the gut onto the skin. Now one of the issues is, and I think maybe we're a bit ahead of ourselves when it comes to selling this product is how do you explain this to people? And also the idea is that if you're pushing it from the gut and you want to see that healthy skin or the delayed aging effect on the skin, then you should not be applying too many topical treatments. Because if you do that, then you have a bit of a problem. Right? You're trying to push things out from the gut onto the surface, but at the same time you're applying something onto the surface and pushing it back in. So. But that's what the white skin is. It's that exact ingredient. And in addition to, we have done other, other studies, these have not been published yet and they are more consumer orientated where we have looked at the effect on the skin and we have a significant effect on skin components using the skin scanners over a period of three months. But that was different study. Even in those females in that same study we have looked at those components as well, but they're not, they're not included in the publication that you have seen.

Awesome. There was a slight delay when you were speaking then, so you were mentioning something around the benefits being pushed from the gut onto the skin. But then the connection kind of broke a little bit. So maybe just explain a little bit how that mechanism works.

So the, the guts and skin are connected through the immune system again and everything that goes on in the gut eventually shows on the skin. So if you are able to balance and reduce the impact of those inflammatory compounds that we talked about earlier, eventually you're going to see the effect on the skin not making you look 10 or 20 years younger, that that's not the effect, but making you look healthier. Making you look. Yeah, well, that, I think that's probably the best term to use. So making you look healthy, delaying that aging effect that would come from inside your body and your lifestyle and your environment and your age and everything else.

Perfect. Summary, I think it, it lends to the creed of this concept called inflammaging. I think it's been circulating in that kind of wellness community for a long time. So this particular compound has the ability to perhaps mitigate some of those inflammating risks. So that's perfect. We better start to wrap. We're going to run out of time pretty soon. Just, just a couple more questions. Being, being someone, Dr. Yelena, on the forefront of this microbiome microbiota research.

What.

Do you think is the future direction of this research and what are you hopeful about?

I do think we're at the crossroads at the moment where a lot of effort, a lot of brains, a lot of minds, a lot of work and a lot of money has gone into the microbiota microbiome research in the last 10 or so years. And we've come to that realization that we have some issues with the modulation of the microbiota which has its place and should never be abandoned. I do believe that postbiotic concept or the similar application, so extracting the benefits from the microbiota, which we know and have, we don't have anything clearly 100% defined, but we do know quite, we know enough at the moment to go down that route is the way forward. And I do believe that a lot of labs and a lot of companies and a lot of people within this field are starting to at least think about that concept. So I see that as the next generation, let's call it like that of works and the products and so on, that will be coming onto the market. And that is until we're able to answer that question, what comprises healthy microbiota. And then we can go back to where we started 20 or 25 years ago of just modulating the microbiota in order to exert the benefits.

That's amazing. I'm so excited for the future. Do you think that the advancements in artificial intelligence technologies are going to help in this field?

Definitely, because. I have different opinions. I'm in favor of artificial intelligence for a lot of the things. For some others I'm not. But in this case, artificial intelligence I think is extremely beneficial because you can one deal with a lot of data with a lot of information. In our case, we are using artificial intelligence to feed different components, different data, different chemical structures in order to. And I think where artificial intelligence in this case is going to be most beneficial is for personalized nutrition and personalized medicines or the treatments. Because eventually when we get enough data from the response of a human and also enough data from all these different compounds, we will be able to design treatments and design products that are on a personal basis, taking into consideration genetics, environment, and all these complicated things that at the moment we can't really deal with. So in that thing, in that case, I think artificial intelligence is not only beneficial, but will also become useful and is already a useful tool.

Amazing. In complete agreement. I think that with the advancing of these technologies, it's such an exciting period of time to be alive. And I'm really excited to see where the, the technology leads us and what advancements in microbiome research result from that. Dr. Yelena if there was one thing that someone could do for their gut health today, what would it be?

I always, I get asked that question a lot. I get asked the question a lot of what should I eat? My response is that the one thing that one should have in life is balance. And that goes for everything. It is. You've got to do and eat everything. And that has to include bad as well as the good aspects. Because there isn't one thing that is so good for you other than sleeping, drinking water. You know, there are those basic things that you should be doing or eating every day. So moderation and variety will result in that balance. And that is, I think, one thing that everyone should take and do, moderation and variety in order to have that balance. And if you have that balance in your body, with your lifestyle, with your diet, with everything else, your gut should be fine. Of course, if you suffer with certain conditions and so on, then you've got to concentrate on those. But we're talking about, you know, people who, who are supposedly healthy.

Wonderful. What a perfect way to end the show. I'm deeply appreciative for you coming on and sharing some of this amazing, cutting edge science to our audience. So thank you so much, Dr. Yelena Vulovic. I hope I've said that correct.

All good.

Thank you so much.

Thank you. Thank you for inviting me. It was a pleasure talking to you. Thank you.

Thank you.

We hope you enjoyed this episode of the Gut Health Gurus podcast with Dr. Jelena Vulovic. If you found this podcast valuable, leave us a kind review and five stars on Apple Podcast, Spotify, YouTube, or your favorite podcasting app. If you want to connect with our host, Kriben Govinda, please follow him on Instagram, Facebook and TikTokthealthgurus. Also, check out our Gut Health Gurus Facebook group. With 17,000 members ready to help you on your journey to amazing gut health, this episode is sponsored by Nourish Me Organics. Head to www.nourishmeorganics and use the code Happy Gut for 10% off. Make sure to check out their range of gut health supplements until next time.