The Vaginal Micobiome with Professor Sarah Lebeer: a Triumph of Citizen Science.

Hello and welcome to the Microbiome Medic's podcast. I'm Dr Shivamak Ormak and I'm Dr Shina Fraser and we're your co-hosts. We are both GPs and lifestyle medics with a shared passion for microbiome science and we have spent the last five years deep diving into the world of the gut microbiome. We'll be translating the evidence and packaging it into actual bite-sized chunks so that you could harness the power of the microbiome to improve your own health and that of your patients. Just before we start this interview we'd like to remind our listeners to take a look at the Gut Mic Bion for Clinicians Course. It's available through BSLM.org.uk. It's a comprehensive course on the Gut Mic Bion which takes you from the basics to the clinical application of this fascinating new area of medicine. This course will empower you to use microbiome science in your daily practice. Hello and welcome to another episode of the Microbiome Medic's podcast. I've got Shivamak Ormak with me. I'm Shina Fraser. We're both busy GPs and we are both obsessed with everything microbiome. Today we're going to do something slightly different. All up until now we've really been focused on the Gut Mic Bion which is of course the biggest human microbiome we have. The most in depth and the most studied human microbiome. It's important to realise that this body of ours houses lots of different microbiomes and actually some of them are fantastically interesting and are just as important for human health as the Gut Mic Bion. What we're going to do is this episode is going to be focusing on the vaginal microbiome which is one that I think a lot of people might not automatically think of as being an important microbiome in the human body. We do and Shivamak has interviewed somebody who is a scientist and an expert on the vaginal microbiome. Shiv, tell us all about your interview and tell us why we decided to do this. I got to speak to the super busy Professor Sarah LeBier who is an amazing microbiome scientist who has really dedicated her whole working life to this area. She is a professor at the University of Antwerp in Belgium. She runs the LeBelab and she's got a group of people think about between 2030 that study beneficial microbes and particularly her passion and obsession is lacto-bacillus and lacto-bacillai. She looks at the genus of microbes and their ecological context. She looks at the evolutionary history and she's really trying to deep study the core mechanisms behind the beneficial potential of this incredible group of microbes. I was just so fascinated by what she was saying. She was so interesting and she's so knowledgeable. I could have honestly, I could have spoken for another two hours. What were your thoughts? Well, we're only doing one episode dedicated to the vaginal microbiome. We want to make it a good one. I think that this is a really interesting project and there's a lot of very important information that comes out in this. You are going to get a lot of very, very interesting information on the vaginal microbiome. I think, have a listen to this, but what I'm interested in is taking this knowledge forward and thinking about how we can use this knowledge. As a GP for me, I want to know the practicalities. I want to know, okay, we have this knowledge about vaginal microbiomes and what kind of species are in there and this is what you're going to find out in this interview. How do we then apply that knowledge and relate that to the sort of diseases that we see in the vaginal microbiome and throughout different times of our life? That was a really interesting thing about this. It's really important to remember that the vaginal microbiome does change throughout a woman's life. It's very, very different pre-pubertals. It becomes different again in early puberty. It changes in middle years and with pregnancies. It changes again postmenopausally. At different stages in a woman's life, they're going to have different issues with the vagina. That can make them more prone to different diseases. It's really interesting. I think, as a GPS, a lot of women with issues and diseases of the vagina, and it's important to know how these come about and how we can prevent them. I think it's probably helpful for us to just discuss the most obvious differences between the gut microbiome and the vaginal microbiome. The listeners on this podcast will be aware that the gut microbiome, we're always talking about a more health promoting ecosystem is one that has increased diversity, richness and abundance. We want lots of different types of microorganisms. The vaginal microbiome is strikingly different in that they're looking for reduced diversity. They are more health promoting vaginal microbiome contains mainly this genus, lactobacillus, which is a very complex genus and has many, many different species and subspecies in it. They describe five different types, I suppose, that are mainly dominated by one or other of these lactobacillus. The four main ones in the vaginal microbiome are lactobacillus chryspatus, lactobacillus innus, lactobacillus gentsanai and lactobacillus gacerai. Do not worry about the names. I'm just showing you that there are four different types. There's a fifth type, which is a more pathogenic community state type, which is kind of a mixture of pathogens and erobs, things like Gardenerella and Previtella. Don't worry about the names. Just know that there is this less, that I suppose, this more. It will be the equivalent to a state of dysbiosis. This is a state that's associated with bacterial vaginosis and other vaginal disorders. I'm going to hand you over to the expert. I mean, one of the world's experts in this area, the wonderful professor Sarah LeBierre, who I start off by just asking her how she became interested in this area. Here we go. Yes, actually, it's a very important area. I have a master in bioscience engineering. It doesn't exist in every country, but it's in a typical Belgian degree where you want to explore all aspects of the human body, animal body, science and more biotechnology centered. I got into the field of the microbiome when I did my master thesis. I could choose a topic. I had a professor who was working on pathogens, but also on this new field of beneficial microbes and probiotics. I was really fascinated by the beneficial aspects of microbiology. I actually started in the field by studying the mode of action of a well-known probiotic and how it could improve gut health and reduce gut inflammation. That was my PhD research. I met another professor working on HIV and he was fascinated by the way. I wanted to explore whether the normal bacteria in the vagina could help women protect against HIV infection. That was my first introduction to the vaginal microbiome field. A few years later, I had an opportunity to start my own research group and, as also typical for this podcast, so many people are already working on the gut microbiome. For my own research team, let's focus on microbiomes of the human body, whereas less research. We decided to focus on the vaginal microbiome and also the upper respiratory tract microbiome and also a little bit on the skin microbiome. I'm really fascinated by the daily light aspect of the microbiome. I collaborate a lot with GPs because I think a lot of diseases or disorders or discomforts are linked to the microbiome. We don't know a lot about it yet. Yeah, it's really interesting what you say about the gut microbiome, which is what the podcast has focused on to date. You'll be pleased to know that the first area we're going to explore outside the gut is the vaginal microbiome. It's incredibly exciting to be with you talking about this today. I think it's one of those subjects in society that's either when people talk about the vagina, they talk about is either sexualized or medicalized or sanitized. It's this wonderful opportunity to reframe our conversation in ecological terms, the idea that we've all got these incredible microbiomes that gut is the best known. The podcast has talked a lot about the gut microbiome. Can you introduce us to this metropolis, this microbiome in the vagina? Can you tell us something about it? There's one thing that is linked to the gut microbiome because anatomically there's an interruption between the gut through the anal region and the vagina. It's a totally different environment. It's what I, as a microbiologist, I like to see it as it's like a bio-reactor. It's a whole collection of microbes we females have in our body. It's a very highly concentrated It's right. Sometimes even the densities as high as in the gut, but it's a much in ecological terms, it's a much simpler community. So normally when women are healthy, they have only a few species that are dominating or really living in the vagina. Typical species are lactic acid bacteria or lactic acid. And they have a main function and they're reproducing lactic acid and that lactic acid, the main function we always think is that it keeps pathogens away. So it makes sure that our crucial organ or crucial reproductive tract is protected against pathogens, either bacteria, yeast or fungi and even viruses. But with my team, we also always say that this few on the vaginal microbiology is really too simple. They will do much more than just producing lactic acid and keeping pathogens away. It's like a whole metabolic organ with a lot of extra functions we don't know much about. So just going back to what you said, because when we talk about the gut microbiome and we're trying to work out how we can describe a more health promoting gut microbiome, one of the things is increased diversity, richness and abundance. So what you're saying about the vagina microbiome is that it's more health promoting is if it is less diverse, if it's just lactic acid line, would that be correct? Or how is it? What's the framework you use? Yeah, I think the framework is indeed the opposite. So the less diverse, the better. It depends a little bit on what are then the dominant bacteria. So we know if there are more lactic acid bacteria and if they're the dominant ones, so the community is less diverse and it's associated with more healthy outcomes, so less problems with pregnancy, less problems with inflammation or net retinas or unpleasant order. So the less diverse seems to be the dogma, although we are not sure yet. It also seems to depend a little bit on where people live and there also seems to be some hidden diversity on the meat. So I think the idea is not that you just need one microbe in Europe or China. There's still a community of different microbes collaborating together. Yeah, which brings me on to lactobacilli because when you're new to this area, it's very easy to think bifurdo bacteria is one type and lactobacillus is another type. But this is this very complex and heterogeneous group of bacteria. Can you tell us a little bit more about that? Because it can sound simplistic to say it's just lactobacilli. Can you introduce us a little bit to this very complex family of bacteria? Yeah, so in the vagina, the genus lactobacillus is important. It's one of the most Asians groups of bacteria and there are actually four species that are commonly found and the most important one is lactobacillus spatus. For example, in our own Belgian cohort, we found that around 43% of the women are dominated by lactobacillus spatus. Then you have a second species, which is also important is lactobacillus inurse. It's also very prevalent around, I think more than 20% of the Belgian women have lactobacillus inurse, dominus, micro-mode community and then we have lactobacillus jensenine, which is number three and we have number four is lactobacillus casseroid. These are the most common lactobacillus species in the vagina of women typically living in western areas. There are different species and they have a lot of common properties so they all produce lactobacillus acid. But I also have a lot of differences in different metabolic capacities, different, a little bit different, many factories producing other molecules. Actually, we don't understand why only these four species are so common and we also don't understand why one woman has a crispatus dominant community and the other woman has an inurse. We also don't know whether they can also co-occurse. So sometimes you have to just have a mixture and sometimes you switch after menstruation for example, one woman can become inurse dominated and the next cycle she has crispatus. So there's a lot happening in the vagina that we still need to explore. I think a lot of people still struggle with the idea of microbes being beneficial. We're in a world certainly with my medical training. We only focused on pathogens or these microbes that caused or could potentially cause disease and vaccinations and antibiotics. And of course with the COVID-19 that's pushed people even more towards this idea that all microbes and viruses are negative to health. But what you're saying here is that we have this community of microbes living in the vagina that produce lactic acid which presumably drops your pH, makes it more acidic which is deter's potential pathogens. Would that be correct? Yes. In this, that's what I really love about studying lactobacillus because I'm studying them for more than 20 years. The fact that they're real core beneficial bacteria. So they don't have any violence properties. They don't like all the potential toxins. They're actually also producing molecules that improve your immune system, that reduce inflammation. They're very soft bacteria. They also promote even good interaction with your mucosa. Maybe they're only little disadvantages. Sometimes they produce a little bit too much acid and can also be a disadvantage. But they're really good examples of beneficial bacteria. So when I focus there with my question on just the pH, that's far too simplistic. That's just one of the many things that they do. So we're talking again and similar way to the gut microbiome that you're getting conversations or cross talk between metabolites produced by these vaginal microbes and presumably the epithelium and even more distant organs with that big correct is there that sort of thing going on? That's definitely correct and that's also the fascinating thing. I think the cross talk between the bacteria and the immune system, it's becoming, it starts to become the explorer and we start to better understand what they're producing, how it can interact with certain immune receptors. The cross talk with other microbes that has long been ignored because they thought of a simple community they can live on their own. For example, at this paper we recently published in Nature Microbiology, one of the most novel findings. We novel things we discovered was that they collaborate and we see networks of even lactobacillus, different species co-occurring. So they seem to need each other for food, they exchange nutrients. Another fascinating thing we recently discovered in the lab is that some vaginal lactobacillus produce vitamins like vitamin B2 or riboflavin and even folic acid which is also important for women's health. There's something really fascinating and now we are saying why would they produce it to promote the health of the woman in which they live or is it also because they also need vitamins themselves and they need to grow and they exchange it as a nutrient. But for example, a metabolite I never thought they would produce but by serendipity we found it in the lab and another area I'm really fascinating but we haven't done real work and if we just know that some genes seem to be present in the genome, it's that they seem to be able to produce neurotransmitters or at least neuroendocrine metabolites and I really would love to explore better day. If they produce it, whether it can go to the bloodstream and even have systemic effects because you were mentioning adjonchrines work and the psychobiotics and we all think about them being present in the gut and I would love to explore better. A slimmer mechanism is happening in the vagina. Well Sarah, that is absolutely fascinating and it's just ringing so many bells from, you know, looking at the gut microbiome and I suppose sheen or an eye when we talk about it, it's really this incredible communication between you and your indigenous microbes and that they talk through these different channels if you like. So we talk about different languages, we talk about immune languages, we talk about hormonal languages and it's this wonderful idea that they're producing all these metabolites that are communicating with other tissues and organs in the body. And just going back to the B vitamins because I think in the gut I'm right in saying that the gut microbiome, microbiota can produce all nine B vitamins so you're saying it could be similar in the vagina as well. Yeah, we at least we know that some species they produce is vitamins so we know I'm a molecular genetic so we've seen genomes that have the capacity to produce it, we see it in the lab, we see it when we isolate them from the vagina where it's really happening in the vagina and has a function we don't know yet but it's, I think about what is happening in the gut microbiome research, I think it must be there or it must be possible. That's really exciting. What I think we should do Sarah then is go because you've mentioned this paper which is fantastic. I've got it here. I know I'm not meant to print things out and I'm meant to be reserving paid. and trees but I am a bit old school and when I get a nice paper I like to feel it and scribble on it and look at it so I printed it out. I really understand I have the same. Yeah so if I can say so it's called a Citizen Science Enabled Catalog of the vaginal microbiome and associated factors it's published in a very prestigious publication Nature Microbiology was published in October 2023 we will put links we really encourage people to have a look at these papers we quite often each podcast we usually introduce one or two papers and even if there's people listening out there who you know don't have a site's background these papers are so beautifully sort of produced that actually if you just look at the abstract the introduction you can learn so much and this one is really lovely because it's a collaboration between you and your very clever scientist in your laboratory with citizens and so tell us a bit about it and what it's named after and why you started it. Yeah the reason I started this was I was I already told you that I was studying HIV and infections in the microbiome and how the vaginal lactobacillac was liquid in hybrid pathogens but at certain moments actually we don't know well what's happening under normal conditions in all women and under healthy conditions so I wanted to take a step back and study the biology of the lactobacillac it healthy women and typically and I think it's the same in gut microbiome research but also in in in monology what people do is using mice or animal models to study to explore fundamental questions but one thing you need to know is for the vagina in mice there no lactobacillac so the vaginal microbiome is totally different and there's actually no animal where you see these dominance flexors so it's lactobacillac it's really something typical for humans and it's something that really fascinates me why is that the case. So I thought yeah I want to study the dominance of lactobacillac why humans have this unique association and I want to study it in healthy conditions so and now the only way to study them properly is by having human volunteers willing to donate samples now these are very intimate samples I've done some other microbiology project in the in the past and I was just pitching to my friends so I have this new idea I really want to study it I work studies outside the hospital without gynecologist but just self sampling would you be willing to participate and then I don't remember is it how Sarah it's it's a nice idea and it's important but you'll have to embed it in a little bit in a in a nitrogen sampling campaign you have to think about communication and so we thought yeah indeed if we are going to ask women to donate samples we have to give them back something in return we have to it's a unique opportunity to talk about microbiome in general but also the channel microbiome of the vagina in general and it's a part of the human body many women don't know all the details about it's linked to so many things menstrual menstrual cycle hormones either way we feel our sexual activity and I want to do it in an honest way so I decided to spend time on the recruitment campaign I also thought it would be quite difficult so I wanted to have a good interaction with communication specialist sociologist GPs very important and they they told us that many women that come to their practice they have problems with their vaginal health and often they don't really dare to ask or it's part of another question so we spend a lot of time interacting with them and asking them what do we think we should study my interest is a microbiome but what's your interest also we talked a lot with with how to say sexual education non-profit organizations we have re-embellagem and then in the end we said okay let's go for a microbiome sampling campaign but on one hand but it in a bi-directional way so that we have also things we can do in return one of the first thing we had time to do was decide on a logo and we and on a name so we named a project after Isala van Ditz Isala is a first female doctor in Belgium she studied more than 100 years ago actually she was not allowed to study medicine in Belgium she had to go to Switzerland as she came back with her degree she wanted to open a practice she was not allowed because she was a woman they had to really change the law and then she was allowed to open a practice in Brussels and from the beginning she was really focusing on women's health and vaginal health because for example she also had a lot of prostitutes in her among her patients so she was also really to honor her and also the logo of the project for example it's like an underwear logo with some nice pink and petrol blue colors and for me the key thing was that it was a very scientific project but not only that so we have we want to have a lot of humor and a nice ton of voice and we wanted to also have a tote bag and some like a nice sampling box not too medical but also to honor the the woman participating and then we had interactive for example we had conversation starters and we asked women what should we explore what should we add to the questions we will ask what do you think is important and so that was a start of all yeah what we call a citizen science project and then co-creation of projects oh that sounds wonderful and when I was reading through the paper I think you know introducing all these different areas and all these areas of expertise and citizens themselves I mean how did you find what was the take up and what was the response so yeah actually so we did all the efforts because we wanted to recruit 200 women because at that moment we had a look in the literature I think most studies were with up to 100 individuals and even though we knew that the for general microbiome is not as diverse as the good microbiome we really wanted to explore diversity in a proper way and so you need enough samples so we thought okay we 200 we would already be one of the best studies in the world and so we did all the efforts for the 200 participants everybody told us it was going to be very difficult the own world as it will be difficult to recruit them and you will have to pay a lot of attention so then we were ready to launch a call and we chose international women states or eight of March and then COVID the pandemic started so we decided to postpone but then at the end of March it was always been so much efforts and everybody's telling us that it will be difficult to start this project so we thought okay let's just launch a call and we just small press release and we will use Twitter and our Instagram with the young RPG students and my generation and all their generation but the response was overwhelming I think within 10 days we had more than 6,000 women willing to participate there was no shame at all the whole family is aware of willing to participate there was so much and to see as many women as it all finally it's important to explore and we will study that so really dense wow that's you know it's an incredible story because I'm just thinking when the NHS when we try and make people come in for tests or tests for a sex trans bit of disease you know you're constantly trying to get people in I think we frighten them away it's very medicalised what happened here that you because I've read that within 10 days you had over 6,000 people registering and you actually have to close it down what's going on here where's this energy and enthusiasm and wanting to belong to you know something like this what's happening what's your thoughts on it I think that was happening at some people said yeah it's it's part of what's we have one to take help into their own hands and it should not be medicalised too much so that was also important because we had very good kind of colleges university kind of colleges participating but we said no we want to take it outside the hospital it's not medical it's we we we're all studying the normal function it's not linked to disease we want to also highlight that a lot of things are probably normal so that we want to scan the whole health spectrum not alarm people and many women felt the sense of belonging so the nice thing is we didn't prepare for it but a lot of mothers which are daughters participates we had grandmothers and grand then the grandchild participating we had people in the elderly home willing to participate and in the sense of belonging okay let's and many women we did a feedback survey afterwards they said yeah they want to do something in return to other women so some said I have three healthy children I want to help other women in the future because my little data point might it's a little bit part of a whole collection but I can help the future generation of women with certain solutions we are not even aware of and other women they gave us advice I'd might be nice maybe you can also add a question on the type of underwear we were because I think it's important other women said are you all should also ask about food intake and we collect all all all suggestions and then we we added some to the to the question here so we I think it was also said like we made 10 amendments to the ethical committee file because we had so many tips from from the citizens to include the Sarah what What you're saying is when you're calling these women, citizens, and scientists, they truly are contributing in so many ways to the science and to how science is done. I suppose I find this incredibly interesting because I looked at the age range from 18 to 98, you had samples. Yes. And it's just wonderful, all these generations joining in wanting to learn more and contribute. And I think for me reading through this, it was a real reintroduction of the vagina into society as something other than what we're used to. There's a lot of stuff about people being concerned, people don't understand the vagina, what it looks like. Young women now aren't really taught about it. They don't know what's normal, they don't understand physiological discharge, or that slight odors can be fine. And people are made to fear this area. So as I said, it's all medicalised by people like me, when we ask people to attend for their smears or to get tested. And actually it's this beautiful organ that is doing so much good and has this community of microbes that are protecting not only the women but their partners, their offspring in so many ways. And it's just a lovely new perspective. Yeah, indeed, thank you for this nice summary. I think that's a whole message that came out of this study. And I also learnt, I think it's important to highlight a way I think when we started, we had a small team of maybe five core members designing the project. And we don't know everything, so it's so nice to collaborate with citizens and really take them serious because so many people have knowledge from their own experiences and they can be very valuable. Also for us as scientists, when you design, especially in projects related to microbiome, because every lifestyle, every environmental factor could almost have an impact. So you need to find a way to make choices. If it's only based on what's already in the literature, then you will just replicate what's already known. So you need to have enough novel sources of information for projects like this. Yeah, because you didn't just collaborate with citizens' sciences. I love the way you were collaborating with experts in nutrition and sociology and people who could communicate and also marketing very stylish, very fun, very human based as well. So it's a very joyful project. But we're talking about the lactobacilli and can you tell us a bit more about the variations? Because obviously if you're going from women age 18 to 98, what were you looking at? What are the other variations in terms of things like pregnancy or stress? So how did you tell us more about that? Yeah, very good points. So the whole idea was that we asked women to donate the sample so we could see their vaginal microbiome profile in a way as the community composition. But also we had a questionnaire. It took women almost one hour to fill in all these questions about lifestyle. And then we wanted to make a association to understand, okay, when you, for example, when you get older, do you get less lactobacilli or not? And age was, for example, a key factor we asked. And then we wanted to rank how important they are. So it's age the most important factor that determines your microbiome or if it's something else. And what result is age is important. So the older you get, the less lactobacilli you have and that's a very important point of attention. So we're going to link to the menopause because what's now well established is that you need estrogen to promote the glycogen production in your vaginal epitelial cells and this glycogen is a sugar source. It's the food for your vaginal lactobacilli because you don't have direct food in your vagina. So you need the source for nutrients for your lactobacilli. So if you have less estrogen, you will have less lactobacilli. But the picture was more nuanced. The good thing is there are still many women above 60 years old already, they have passed their menopause but they still have lactobacilli. So it's not all bad. And there are women. So it's not only menopause. It's something, and menopause was not the most important factor, determining the vaginal microbiome. So it's something we want to explore further because maybe Belgium, we know a lot of women take hormone replacement therapy and so on. We have to dig deeper a little bit. So age has an impact, but it's not everything. Then the second on the list, the most important thing was having had children and that's something we did not expect at all. So if what we saw with us, if a woman had a child, a child, given birth to a child, even if she had a miscarriage or an abortion, we saw less. Less of lactobacillus crispatus. So one species of lactobacillus, but more of lactobacillus gastro, so another species of lactobacillus. So it changed in species diverse. And we saw also more beefy dog bacteria and they are important for the small babies and also more streptococcus. So it was not that it was a worse microbiome after pregnancy but a different microbiome and we don't understand that at all. So we have discussions now what's happening during pregnancy? Is it because of the hormones, because of the anatomical changes? But because we also know already from other research, if you get pregnant again, then you have again more lactobacillus crispatus. So it changed again. So there is a link between the ski life stages. It's happening, but we cannot fully explain it at the moment. If I can just ask you one thing there, Sarah, because we've talked again on the podcast about the importance or the relevance of a mode of delivery. And again, we talk about essentially being sterile at birth, although I know there's some controversy about that. But if we assume that at the moment, as the baby comes through the birth canal, they collect these pioneers that then go to the form, the initial gut microbiome in the offspring. But we often talk about it coming from the mum's gut. Do you think that we're going to find the vaginal microbiome, the mother's microbiome, what she gifts her baby as she passes through the canal is going to be more important when you talk about the bifidobacteria? I think they're important. But what we know from literature and from our own research is that the vaginal microbes are also being transferred to the babies. They will be even part of the gut, but also on the skin. In the gut, they will not like the cylis CRISitis. It's very much adapted to the vagina, but it cannot survive well in the gut. So it will rapidly be buried under all the other incoming microbes in the gut, but it will be there in the beginning. The bifidobacteria, they're also living in the vagina. They can also be transferred from the vagina of the mother to the guts of the baby and the skin of the baby. And they can survive in the gut. So I think our study was one of the first to show that bifidobacteria, they are dominant. They can be quite prevalent in the vagina. So I think now in the future, where we want to really see what we call strain, the same real bacterium is transferring from the vagina to the gut of a baby. For that, you need very good tools. And it would also mean the same. For example, we also find the mostly lactobacillus, which are types of lactobacillus. They live in the vagina, not so dominant, but they are very good at surviving in the gut. And they also think that they will be transferred from the vagina to the gut of the baby. So it's open to all new areas. But yeah, you know, you're a GPS, so you know, during a delivery, of course, there's also a stool being transferred in this vagina, fluid being transferred. So it will be very difficult to dissect at all. It is difficult to dissect. But again, we're talking about narratives about women's body and women's health. I think it does change the narrative because it's one of those things when you hear groups of women discussing their fears about giving birth, they're really embarrassed that they might pass some stool or they might, you know, urinate or they're. This completely changes again the narrative that actually this is a, you know, a really important part of, you know, your babies gaining these important pioneers, these important bacteria. And it does change the story and perspective into a much more, you know, positive one and embracing, you know, all parts of our body, even those that society have put a big taboo on. I think we need to kind of break that taboo and, you know, embrace all this incredible information. So you're talking about age and pregnancy or parity as important, sort of, to the variations in the vagina microbiome. What about periods? Did you ask people what part of the cycle they were on or? Yes. So I think that was the type, the cycle was very important. You have the luteal face and the follicular face, so the face where you have a lot of acid. estrogen, you have also more lactobacillus, so that's crucial. So it's also connected to the fact that even when we're on birth control pills with estrogen, they also had more lactobacillus crispatus while they were using an spiral or intrauterine device with more progesterone, then they had lower levels of lactobacillus. So the hormones are, I think, next to age and having a children where the tourette major driving factor of the community composition. And what about you did mention that most of it was on, obviously in Belgium, the European women, what do we know about racial or ethnic differences in the vagina and mycrane composition? That's a very good question. I think it's one of the most also, in a way, how do I freeze it? So one thing, maybe first, say one thing, because we work so closely together with sociologists and communication specialists, one thing we did not ask was women, what's your race or your ethnic group you belong to, because it's like it is often connected to the way people live and where they come from. So we just asked them, where are you born? How long do you live in Belgium? And then we also asked about their lifestyle habits and what they eat. And so on, because we thought, yeah, for the microbiome, it doesn't really matter what your skin color is. All these other factors matter, because there are some very famous or the big microbiome, babies who say that women from a black ethnic group that they have a less beneficial microbiome that they have less lactobacillus, more gardener relus. And we think it's really biased because often they're from a lower socioeconomic status. They have less access to good food, less access to healthcare, and that also can get all impacts. So it's very crucial that this link to race and ethnicity should be carefully interpreted. So and there are also, for example, there are studies that also people, not only in investor countries, but also people, women living in Africa or in remote areas that have a less beneficial microbiome, again, less lactobacillus, but also we don't know that whether they were, how were they sampled? Some of the studies are in sexual or with sexual sex workers. And then of course, it's not the general population. So the tendency or the view now is that in other countries and Western countries women have a less beneficial microbiome, but I don't agree with that. I think it's just there are some mistakes being made in the sequencing. So that's one of the reasons we are also now starting our assistorhood project and we ask women from different countries to launch a similar project and really targeting healthy women and sampling. And also to understand that maybe they have a different microbiome, it less lactobacillus, but it's still a beneficial microbiome having the functions, keeping women alive because there are many, many parts of the story that could still be beneficial. So we want to avoid phrasing that's been from under-contestive, less beneficial microbiome. We don't know that. I think it's a very, very important point you raise and we know from the gut microbiome you can't say good, bad, healthy, unhealthy because we don't know it's far too complex. It's like looking at a community in a city and asking if they're good or bad. It's just impossible to say it's all to do with not just who's there, but what are they doing? And, but I think we need to be very sensitive about how we collect information, how we phrase it. And I suppose one of the things I really liked about your project was this idea that rather than people as subjects that are investigated, this was very collaborative and very empowering and finding out about yourself and your body and your vagina and your community and contributing to knowledge seems to me a really exciting way to think about doing science in the future, empowering people to want to take part rather than taking samples and then judging them against some arbitrary scale. So it is interesting. It's also interesting to me because you can get these huge numbers. And I think if we look at one, I don't know if you call it, "Sitants Science" or not, it started as that, the British got project which then morphed into Zoe and this, you know, people sort of argue, but they're getting huge numbers. So instead of I'm sure you'll be used to try to get, as you said, one or two hundred people in a trial and you're actually having to shut down your trial because you've got 6,000 registered in ten days. I mean, it's really exciting because obviously the higher the numbers you have, that's going to eye out some of the issues with research. So what are the pros and cons of doing science like this, as, you know, when you look at the project you did? And can you give us two or three things that are foreign against doing this sort of citizen science project? I think one of, you already mentioned, one of the pros is that you have a lot higher numbers for your trial. Also that it simulates, it's citizen-reviewed so you have your trial will be more. society-relevant and you know that you ask right questions. What I also liked about it is that we had a fun factor and we had also a nice design and we had a. It was really a collaborative effort of the team. I learned a lot from it so it's more rewarding as a scientist to do this trial because you have more sense of belonging and that you're doing things that matter. And for example, we had a lot of postcards from participants who said, "Oh, we love your project. Keep on the good work." So we had like, "Oh, people value what we do." So that was really nice. Cons, yeah, cons are, for example, it's much more expensive to do it. It takes time. I have a big group of researchers and I'm very, I think, work-life balance is very important. But if you're doing a citizen science project often we had to re-plan and we had to work a little bit later because we had to translate our website because suddenly we saw people from England were washing and so we had. We did a lot in addition to the normal working hours. So it's not something you can do every year. For example, you know it will be a hectic time. And maybe a third major disadvantage is that some things are out of your control. So if, for example, we did sampling projects in the past with gynecologist, they take a vaginal swap from a dedicated place in the vagina. They know where it comes from. They put the sample immediately in the correct file. It's going to the freezer and everything is unproperly. While now women took the samples themselves. We advised them how deep they had to be. We also said how many times they had to turn and then put the swap again in the tube and then bring it in the fridge and send it to us. But it's out of our hands. We didn't. We were not there. They did it properly. Sometimes it took one day before it entered our lab. Sometimes it took seven days so mistakes can have happened. But for us it was counteractive by the fact that we had so many samples. So if one woman made a mistake, no problem. We had no other samples. And then maybe also something very difficult was we wanted to study healthy women. What's the definition of a healthy woman? So in the end we said, "Yeah, if women say from themselves they feel healthy and they have a general good health, then for us it was okay because it's a citizen's science and we want to not make it a medical project. So there's no diagnosis, no GP who confirmed indeed you are healthy. Because sometimes it's okay. This woman says, "I'm healthy but I'm a medical history." And we say, "Oh, maybe it's not so healthy." But she was still allowed to participate because that was the idea of the project. And we talk about the ages that you covered from 18 to 98 and I understand that lactobacillus is dominant from puberty onwards. Do we know much about pre-pubety of the vaginal microbiome composition? I imagine that's quite a difficult area to examine and investigate. Yeah, and you did something I want to explore now in the future. So the dogma is again that it's only starts to be puberty that he then gets the increase in lactobacillus because of the estrogen. But there are some studies that it starts already a little bit earlier. And I have my also 13, she's already menstruated. So it's also interesting to see, "Okay, actually we should try to do it in this new generation of girls. I think they would be willing to participate to a trial like that if we embed it properly. We are now all six, but maybe we don't need swabs. So we can discuss with them maybe sometimes the first urine can also be a good sample because it's linked to the vagina. We see the same type of microbes in there. And we want to also do a co-creational project with them. Would you be willing to participate in a project? What's important for you for this generation? Which questions do you have? Because they also need to make a lot of important choices like this, which menstrual products are you going to use? You have now the cup. And you have this new type of underwear and not only pads, so there's so many things that is happening. And it would also be a nice opportunity to break some taboos before they are becoming sexually active. So it would be nice to start a project. not only to answer basic questions on science, but also help this generation which questions they have. Did you ask about things like tampax use, sanitary towels, vaginal doshing, or was that over and above what you were studying at this? I know definitely. We have asked about that. So one of the surprising things for me was that using a pad was negatively associated with lactobacillus respite. So if we worried the 24 hours before then we saw less of the beneficial bacteria. And we saw the opposite for the cup. So we had a lot of younger women already using the menstrual cup and they had more lactobacillus when they, even when they worried before. So tampax did not have a big impact. So maybe it's also good because they're also the additional storage budget toxic truck syndrome. We asked about cubic javing. He had a little bit of impact but not too much. We asked about dosing. We had not so many women doing it. We saw a little bit, we saw a reduction but not really change in composition. We asked about sexual activity for example. And the way we did it was asking women to draw a heart. We had a heart shaped on the tube and then it just needed to color it when that's a sexual intercourse at last 24 hours. And we saw a big increase in diverse microbes coming in. But then after if it was a few days later then it's it went to normal. So it's also part of like it's a normal thing of the human body and it's being tolerated. But just being asked these questions is really empowering for women. Just being able to ask all these you know that these intimate questions are of interest to someone and they're part of who you are. It's interesting isn't it that actually taking part in the project? As you said I can't get people to spend an hour doing a question there and yet they willingly gave up their time and were excited to be part of this. Yeah and that's indeed a good point you raised because we heard from many women that's just thinking about the answers to these questions helped them with some issues there or they were really reflecting and some women they thought that they were answering together and then they were started to talk about it and they started conversations about certain taboo topics which in the end were not so taboo I think that was one of the main lessons I learned that what I thought was was going to be taboo was actually not so much of a taboo. So I would I hypothesize that the project itself did that, destigmatized it and changed it into something that this group of women owned and were proud to be part of and that pride thing is you know yeah so it's interesting how much that your project was not only collecting information it was altering people's perspectives and society's perspectives you know in Belgium in that group of women not you know a large group of women and that will go on the discussion they'll feel more comfortable talking you know across generations it really did open up a lot of conversations I'm sure and it's interesting that doing a science project like this in itself is therapeutic in some way that you probably can never measure but you're getting the feedback I mean how many trials have you done where you get letters from the people in your research study thanking you for you know having them in the research project or you know lovely feedback like that I'm sure it doesn't it doesn't happen. So if all this incredible information that you've got in mapping out the vaginal microgbion in this wonderful group of women who I thank wholeheartedly and you truly are citizen scientists and you're teaching me so much and everything that you thought about wanting to belong to a project is coming to to fruition because we are all learning so much from your incredible contribution. So where does it so we've been talking about we've expanded our thoughts about the vaginal microgbion map we're learning more about the effect of people's age, menopause, pregnancy, their periods, we didn't talk about stress maybe we'll come back to that but drugs particularly HRT and the contraceptive pill diet again we haven't spoken so much about that but where do we move from saying well who is there which bacteria and we haven't even begun to talk about all the other microbes that will be there as well to what are they doing and where are you going to take this project or what can it help you with. One thing we promised the women participating in the future we would love to design novel diagnostics and the other hand is novel therapeutics so for the diagnostics what we now have which is map is that we have a reference map of what a healthy microbiome more or less looks like and then we use it for collaboration's clinicians on all kinds of disorders or diseases and we compare actually we basically compare and we hope to maybe find novel diagnostics for certain diseases and then the other part is we would love to explore certain novel therapeutic options what if you don't have a beneficial microbiome. What if you lack lactobacillus? What can you do? Can we just transfer lactobacillus to this microbiome and will it colonize or does it meet all our friends so how will it work so we are because we did not only store the DNA of the microbiome but we also really store the microbes the lactobacillus we have in our culture collection we have thousands and thousands of lactobacillus for every woman and we are doing microbiology screen experiments okay which microbiome is producing this novel vitamin or novel dichobantibiotic and we because we have so many samples we can do it in a proper way and so in the future we also hope to develop living therapeutics. So Sarah the one thing listeners will be wanting to know is about probiotics I wonder if you could just introduce us to the idea of probiotics for the vaginal microbiome and maybe start by saying what probiotics are. So the official scientific definition is that probiotics are live microordinates that when administered adequate amounts confer a health benefit to the host. So it's a quite complex definition and there are three key elements into it. It means that you have to take the liberty some live microbes in any kind of formulation whether it's an oral formulation targeting the gut but you can also use an oral formulation or oral product that even targets your vagina and then you have to take a sufficient amount which should be there it should be really made with a purpose and you have me to have sufficient bacteria or live yeast can it's also possible and then the third element which is a key element it should confer a health benefit and that's that's very difficult to prove it means that your bacteria should have or the probiotics should have been tested in clinical trials and that trial should have a positive outcome and this trial could have been done in healthy subjects or people without any official complaint or in a disease population but studies in a disease population are very difficult to do with probiotics because there are supplements and officially cannot do a clinical trial for a drug in with patients so the trials are difficult to interpret and choice are difficult to make. Wow because I did when I knew we were going to be talking I did look at the probiotics that are available in the UK and it's like the Wild West it's really complex even as someone who has a some understanding of how microbiomes work and the terminology I found it really complex so particularly for the genomic microbiome some of the probiotics I looked at they mentioned lots of lactobacillus but none of the species which you've mentioned so they seem to have a bunch of gut-related lactobacillus but none of the chryspatis or gastrogynous genus and I that you mentioned I mean what's the landscape in Belgium or how does it work? think the landscape is the same, think there are numerous reasons why current probiotics don't have this vaginal typical species one major reason is that the science is quite novel and it takes some average 10 to 20 years before such products are being developed but a second major reason is that the microbes said that species adapted to the vagina like lactobacillus chryspatis said don't grow well outside of a vagina and so they are difficult to put into a product because they love that environment and the nutrients are available and they have difficulties in growing in this typical fermenters you need an industry to make this probiotics so what what industry is doing is they put other lactobacillus that are similar and they put them into the products which is not always ideal but it will take time but I believe there soon there will be more women's health or vaginal probiotics on the market but let's hope that they will be properly developed. yeah it's really difficult for people because they just go in and see a big shelf of probiotics and maybe look at the vaginal microbiome probiotics and it's complex because it's easier for me to say or just steer away from them and yet I know there's a lot of researchers doing really excellent work who are equally frustrated by the fact that anyone can, it seems, produce a probiotic that says it supports vaginal health, and some of them don't really tell you they suggest two doses or two capsules a day forever. There's no duration, so it's quite expensive for people, and they could be taking something that's quite costly, that there's no scientific evidence of benefit, would that be correct? Yes, that's true, that would be correct. That's also frustrating for us as scientists, because regulations are currently so strict that producers of manufacturers make improvised, in a proper way, they are not allowed to put things on their packaging because they're not drug, so they cannot make any claims. But the disadvantage is that other manufacturers that have less high standards, they can put the same on the package. So for consumers, the only possible solution is to go to the scientific literature, which is very complex, and then double check yourself, because there are so many rules on how manufacturers can communicate on the app. So we're also trying, we're trying to find a way out of, okay, where to set the barrier to make also distinction, okay, sometimes there's good evidence out there, not fully ready to really fully recommend probiotics, but there are differences between different strains and different products and different species, so it can be of benefit. I think what I like to do as a scientist is look at the meta-analysis, all the articles that are out there together, and for example, when people are taking antibiotics, both for the gut, but also for the vagina, that's really a condition where you can disrupt your microbiome, both in the gut, but definitely also in the vagina, so then you're very vulnerable. For the vagina, definitely, you can get yeast or fungule infections, and for me, that's scientifically definitely a case where probiotics could be of benefits. Just a you deeply, you will also deeply select a bacillus, and it will be important to have to replenish them, and so then I would advise people to have, I don't know, yeah, I'm not allowed to say advise, but I think it would, if you want to explore it, it's really worth exploring it, and then preferably one with a lot of a lot of like to facilitate for the channel health, what we are doing in our lab, now in many different trials, is trying to get a better understanding of which lactobacillus IATIC orally, which traces species can really travel from the gut to the vagina, by the natural roots, if I direct them and the area of the skin, you have some transfer, because they need to end up in the vagina. Sorry to stop you Sarah, that's a really key point for me. I have to say, before I looked into this area, I presumed that if you were going to give a probiotic that was going to improve a vaginal disorder, it would of course had to be in a pestery or a vaginal form, and I find out that I'm wrong, and that you can get vaginal probiotics, but also people take it orally, can you explain to me how can that be? I think there's a very good, very good point, I don't take you wrong, you're absolutely right, it's just because of the law, so if you would put a lactobacillus in a channel, what I call formulation, a product that you can insert vaginal meat directly, it would be a drug, then you really need to do different kinds of trials, and that's also something, for example, we would love to do now with our lab, but you need to run a trial like that, you need millions and millions of euros, so they're much more expensive to execute, and it will take time before these real drug products are being developed, so what the industry is doing is just making oral formulations because then they can be studied, but also put on the market as food supplements, but the big disadvantage and you're 100% right is that you only get a lower dose into the vagina of this lactobacillus, you can get, and people have shown also in our lab, we see that they're transferred, so he gets the strains end up in the vagina, but in lower dose, so you might, is that really a problem, we don't know because lactobacillus, they can grow well in the vagina, so maybe you don't need a lot and you can still have lactobacillus production, and the lactobacillus production will help you keep pathogens away, so mechanistically this could work, but as you also feel, it doesn't seem ideal but it might be suitable for the sub, yeah, people who want to do something additional, that it can be of benefits, but as scientists and medical professionals, I think you would prefer the the direct root of administration and also the drug root of clinical trials to explore which ones are the best to use. It isn't intriguing, however, that even in reduced doses, that a probiotic life bacteria you take by mouth that travel down to the gut can end up in the vagina, now I presume that's possibly mainly via the, because the anus and the genital areas are near to each other, or would there be other pathways, because we know, intriguingly, for example, in breast milk, that you can get transfer of microbes from the gut to the breast, which I find mind blowing, could there be such mechanism here, or we don't know. We don't know, I think it's a very good question, I think it could be because we know that dendritic cells or certain immune cells in the gut stay simple bacteria and they can cross across the body, so I, and it's close, oh, close, we linked to it, I think it's possible, but it can also be through the skin, and it's something we would love to explore now in our own going research in more detail, but because it's happening, but in a low dose, it's not, it's very tricky to investigate, it's not easy. So one of the conditions I see a lot of is bacterial vaginosis, which is a common vaginal disorder, which for anyone listening, it's traditionally treated with antibiotics, either in the vagina or more commonly in the NHS orally, metroniders, or typically, which as you say Sarah, causes a, you know, tips the vagina microbiome into an imbalanced situation, and there's a high recurrence rate, and I did see quite good effects from probiotics, which seemed in some aspects to be superior to antibiotics with favorable outcomes. Can you do you know much about that, or? Yes, so I think the meta-analysis are quite positive, and in favor of using probiotics, and for a moment, it's, there doesn't seem to be a big difference between, so you need lactic acid, bacteria or lactobacillus that produce lactic acid, and the good data that are out there are with strains that we know that is ryefwell in the vagina, and I think that the all lactic acid have the property that they make lactic acids. So there seems to be some promise, and I know that many manufacturers are actually now using that, and often also similar strains. There are many women who have benefits from them, but also many others that don't, and that's also something we want to understand, okay, when you give a new lactic acid, when will it be able to have that function in your vagina? Does it matter which other microbes you have, or does your immune system has a role, or your hormonal status, and because you also need estrogen, because estrogen simulates glycogen in the vagina, and the glycogen is a sugar that your vagina lactobacillus needs to grow, and to have sufficient numbers in. So anyone who's listening here who thinks, gosh, this is very complex, you are absolutely right, this is so complex, and I really struggle with it. And as I said, I have got a basic understanding, now most doctors don't, they're incredibly busy, super bright people, but they haven't got an interest in this area which I have, and I'm struggling. Patients are told when they look at probiotics, or when they look at websites, or journals, or magazines, go and speak to your doctor. Now, they are being sent to people who have no training in this area. It's something we need to be looking into. I would love to be able to admit my ignorance, but signpost people to a brilliant, easy to use website that they could put in their disorder, and their details, and find the relevant studies. Is that something that anyone is working on? Yes, I know there are some people working in it. I'm part of the FIsAP, which is the International Scientific Association of Pro and Prebiotics. We are mainly focusing on the science, and we try to stay away from the recommendations, but others are doing this, and I have to look it up, and I can, if you want, I can send you some links, but people are trying to make this guide lines, which is very complicated because we are scientists, we are bound to certain rules, but we can communicate, and you have the manufacturers there, they have certain rules, they are not allowed to make any health claims, so they are very careful in informing the consumers, and they often only give information about your own product, and they don't compare products, which is what consumers want. want. And then you have the regulators who also are especially in Europe, they're very strict on what can be communicated. But on the other hand, you have so many products, products can come on the market without any claim and then it makes it even more complicated. So there's definitely a need for educated people to inform the consumers on which choice, which we chose you can make and what are the options so that people can try based on scientific evidence, they can try products for their conditions knowing that not everything has been proven yet and there's lots of signs that still needs to be done but at least you have some options because I fully understand if you suffer from problems you can sometimes you cannot wait 10 years before the product will be on the market and there are products on the market that based on the current scientific evidence could work so it feels sometimes yeah it's difficult to also give the good advice. It is difficult and I suppose on this microbiomellic podcast she and I try and be very pragmatic because the guidelines for the NHS can take anything from 10 to 17 years to to come and people if they've got a problem now they want evidence-based best-guess advice, a pragmatic approach so anyway we perhaps will do another podcast into this complex area but going back to what she and her and I do which is a pragmatic approach using lifestyle medicine modalities so that's looking at things like sleep, stress, physical activity, diet, is there anything there that has a good evidence-based that we know supports vaginal health? Yes actually that's also what we have studied to our surprise lifestyle had a rather big impact on the vaginal microbiome and in general eating healthy and sleeping well is also beneficial for vaginal microbiota. If you look at our own data on diets and this has also been observed in other studies we see that if you eat a lot of sugar it's not beneficial for your vaginal microbiota we see it's less associated with lactobacillag in the vagina and the other way around if you consume one of vegetables and especially fiber-rich vegetables and nuts and seeds who are rich in phytoestotrons then we also saw association with a more beneficial microbial. Anything augmented food or not specifically for the vagina microbiome? We saw some associations on fermented foods and probiotics we also saw some more beneficial ones but we're not sure yet whether it's direct association or not and it's definitely something we need to study in the more detail in the future but it could be because fermented foods they're naturally rich in lactobacillag. That's really often naturally rich in electric acid so it's biologically possible that some of these microbes also have a beneficial impact on your vagina. Okay that's incredibly helpful so those are positive take-home points that are going to be beneficial to your gut microbiome at the very least and possibly probably your vagina microbiome too and also is thinking of things for people to avoid so you've mentioned antibiotics are disruptors of the vagina microbiome and presuming doshing and over self cleansing could be in that category as well to avoid. Yes definitely doshing is a very bad idea. Using soap is like actually almost the worst thing you can do because soap has a high pH while you're a vaginal microbes they want low pH and so every time you do she would reduce the lactobacillag so that's really not a good idea. Using antibiotics of course also not but even also eating meat or sugars and also if your lifestyle is also not a good idea. Not too much at least. Yeah that's really really good advice. So listen I've taken so much of your time this has been incredible and I have so many questions I want to ask but maybe we can have another podcast in many months time and see where you've got to in your research. How can listeners find out more about this project and future projects that you're doing? So we have a website it's zalla.be/eand for English the English version and they really try to make a summary of all the research that is ongoing but we also have guest people writing block posts and everything related to the general microbiome and other aspects. That's wonderful. We'll put all those links in the podcast so any listeners who are interested will be able to find them at the end. Sarah thanks for your wonderful work Longmeer continue and thank you to the citizen sciences. Those women in Belgium I hope they're listening to this podcast and can see how important their contribution is to this this wonderful field of research and finally I think we should dedicate this podcast to Dr Asal Avondiis who's the first doctor in Belgium only a hundred years ago and you've named the citizen science project after her so thank you so much. Thank you so much for listening to this episode of Mike Bermidik's podcast. We really hope you enjoyed content and we welcome your feedback. We'd love to hear any suggestions you might have for Mike Bermidik's topics that you'd like us to cover and we also appreciate listeners' questions and we'll endeavour to answer them in the next podcast.