Our guest in this episode, Greg Leyer, PhD, has an academic background in deadly pathogenic bacteria, such as botulism and other foodborne illnesses. Now, he focuses on healthy bacteria and joins James to discuss benefits of probiotics for the vaginal microbiome.

While gastrointestinal health is thought to depend on microbiome diversity, the vaginal cavity requires a more homogenous population of Lactobacillus species. By producing organic acids—mainly lactic acid—lactobacilli help maintain a pH below 4, which prevents bacterial vaginosis.

Listen to the full episode to learn more about:

  • How and why taking oral probiotics affects the vaginal microbiome
  • Forms of microbiome supplementation, like probiotics, spores and heat-inactivated bacteria
  • Efficacy of probiotic supplementation in different geographic locations and ethnicity

And check out Dr. Leyer’s ongoing work:

The Vaginal Microbiome with Dr. Greg Leyer | Ep 285

James Maskell: This broadcast is brought to you by the Evolution of Medicine’s Practice Accelerator. For more than six years, we’ve helped doctors and health professionals build their own low-overhead, high-technology practice, making it efficient and effective at bringing in patients, educating them consistently, getting the right technology stack and building a strong, sustainable practice. If you want to find out more about the Practice Accelerator, go to goevomed.com/accelerator.

Hello, and welcome to the podcast. This week, we are going to talk about something that we’ve never talked about on the Evolution of Medicine podcast, the vaginal microbiome. I was introduced to Dr. Greg Leyer a few months ago, and he is a worldwide leader in this area. And there are some things specifically about the vaginal microbiome that are very different from the gastrointestinal microbiome, of which we have had a lot of content over the years on.

So, I thought this would be an interesting topic one, because obviously, there’s a lot of women coming to functional, integrative, lifestyle medicine clinics, and secondly, I think there’s an opportunity for new standards of care when it comes to things like antifungals for yeast infections and for bacterial vaginosis, and some of the issues that you are treating, whether you’re in women’s health or primary care, or in functional integrative medicine. Definitely an interesting half an hour, lots of great clinical content. Enjoy.

So, a warm welcome to the podcast. Dr. Greg Leyer, welcome, doc.

Dr. Greg Leyer: Thank you.

James Maskell: So, let’s start at the beginning. Obviously, probiotics, one of the biggest topics now in health, and achieved so much interest. I remember sitting, watching the U.S. Open one year, maybe 10 years ago, with my old partner, and seeing them talking about probiotics and how it heals the gut and so forth. This has been a very niche conversation that we had had with doctors in our weird world of functional and alternative medicine in the years before that, and now, it was on a commercial at the U.S. Open. I was like, “Wow, times are changing.” So, what got you initially interested in probiotics?

Dr. Greg Leyer: Yeah, great question. Actually, my academic training is in bacteria that will kill you so very opposite of a probiotic. It was all pathogenic, foodborne illness, botulism, things like that. So, that’s what I did my advanced training in, but my first job out of graduate school was with a large pharmaceutical company that had a nutritional division that was looking at this new topic. And this was in the early to mid-1990s, so almost 30 years ago. And how can we use healthy bacteria to promote wellness and disease mitigation, et cetera?

So, it was very early. The stat I like to throw out there is that back in the early ’90s, mid-’90s, there was one clinical study published a year in probiotics, and now, there is one a day. It’s just ballooned in interest and research, which has been great for everybody, the field, the researchers, and most importantly, the consumers.

James Maskell: Yeah, absolutely. My first introduction to it was 2012. I went to a conference, and I saw a two-hour lecture by Bob Rountree on the human microbiome project, and that’s when I kind of realized, “Man, medicine should be turned on its head in the next five years,” because this is almost the opposite of what people had thought about, how they thought about bacteria. And that was actually the very beginning of the Functional Forum. I think going to that lecture gave me the confidence to go in front of doctors and say, “Hey, look, this is happening, and if you follow this to its logical conclusion, we need to really think differently about how we’re treating patients.” So, I guess, let’s just start and lay the table. What is a healthy microbiome, and how close are we to knowing the truth about that, given how nascent this industry is?

Dr. Greg Leyer: Yeah. I would say that we have made steps towards improvements in our understanding of the microbiome. We have amazing tools at our disposal to study it in more detail than we probably could have ever imagined. So, what that leads to is more, “Gosh, that’s surprising.” I would say that, in many cases, marketing is a little bit ahead of the science in what we understand to be a healthy microbiome. I think it’s fair to say that different parts of the body has their own unique microbiomes. If we focus on gastrointestinal microbiome, we feel that species diversity seems to be linked with health and wellness.

If you look at a different location, the vaginal microbiome, that’s not the case. We don’t want to see species diversity. We want to see a more homogeneous population of Lactobacillus species that are strong acid producers to keep that particular niche healthy. So, we’re learning a lot. We continue to learn more. We learn about how bacteria are sensing and communicating with each other. But in my opinion, it’s still a very nascent field with lots more discoveries to happen.

James Maskell: Yeah. Let’s talk a little bit about those different microbiomes for a moment. Is there evidence to suggest that an intervention in one part of the microbiome will lead to changes in other microbiomes in the body?

Dr. Greg Leyer: Yes. I think the example that’s top of mind for me would be oral consumption of probiotics, specific probiotics orally consumed. So, it goes through the gastrointestinal tract, affecting vaginal microbiome composition in some cases. So, we can affect dysbiosis in the vaginal cavity through oral consumption of probiotics. There’s other evidence of systemic effects of probiotics, how an orally consumed probiotic will affect metabolism or lipid composition in blood, specifically LDL cholesterol levels. So, their effects are outside of where they reside.

And then, you have the whole immune component, where a large percent of your immune cells are at the epithelial layers of our intestinal tract, and it’s sensing friend from foe constantly. And oral consumption of probiotics has been shown to affect immunity, improve vaccination rates, reduction of atopic eczema scores in young children, the list goes on. So, there’s definitely systemic effects, but we do know that consumption of even a small number of probiotics, not only in total quantity in billions, but also in numbers—one, two, three strains—can affect overall community dynamics. And that’s really interesting to me.

James Maskell: Yeah, that is interesting. One topic that I got very excited about a few years ago was the communication between the microbes, the quorum sensing. So interesting that it seems like the microbiome actually gives us kind of a lot of lessons for how maybe healthy populations can interact, human populations even.

Dr. Greg Leyer: Totally agree. Quorum sensing is really interesting. It’s also really interesting, some of the work that’s done on trying to repopulate niches with bacteria of similar species. It’s really hard to do that in a healthy microbiome. If you’ve got strain X, for example, and you’ve got another strain of the same species, it’s really hard to outcompete that. It’s a competitive environment. There’s niche specialties. There’s food source requirements, antimicrobials, productions of these things. It’s a real dog fight in the GI tract or in any microbiome space. And the fittest survive, and they’re there for a reason.

James Maskell: Yeah, absolutely. Well, let’s talk about the range of possible interventions. So, obviously, in the supplement category, there’s a lot of different companies with different positions, of different strains that they’ve collected or different value propositions. This one makes it through the gastrointestinal layer. This one needs to be refrigerated because it’s a live strain. Can you give us an overview of what you think is the current state of the science as to what out of that is real and what out of that is marketing?

Dr. Greg Leyer: So, I would say that the traditional probiotics that we’re familiar with… So, let’s just talk about Lactobacillus species, or the genera formally known as Lactobacillus, because that’s changed taxonomy, Bifidobacterium species. Technology exists today to keep them room-temperature stable, not only through how the strains are manufactured, fermented, stabilized, but also packaging technologies. So, they can stay stable, viable, but dormant on a store shelf for 12, 18, 24 months.

There’s other types of bacteria that are being sold as probiotics, like the spore formers, which have an inherent advantage in stability because of the spore, which is like a seed. It’s going to be dormant until the conditions are ready for it to germinate into a vegetative cell. And then there’s technologies that are being developed where people are actually using heat-inactivated cells, where you don’t have that stability issue, but the data is much more young and emerging in that particular field. That’s the whole field of postbiotics.

James Maskell: Yeah, interesting. Well, I’d like to jump in, actually, to your area of specialty because we’ve had a lot of stuff over the years at the Evolution of Medicine, and listeners who are listening to this can go back to summits and podcasts and all kinds of content that we did on the microbiome over the years. It was probably the number one topic that we chose early on, just because every doctor was now subject to this new science. Whether you were trained in functional medicine or conventional medicine, here was a new clinical area where we could really talk about things like holism and root-cause resolution and system thinking and that kind of thing. There’s plenty of content that we’ve made.

Let’s talk about the vaginal microbiome because that’s, I know, an area of your specialty. You mentioned a little bit earlier but give us an idea of what is a healthy vaginal microbiome. And if it becomes unbalanced, what can that lead to in terms of clinical issues?

Dr. Greg Leyer: Yeah. So, what we know today about that, a healthy vaginal microbiome, it’s different from a healthy gastrointestinal microbiome. So, a healthy vaginal microbiome is going to be composed of Lactobacillus species. This is actually something that’s recorded in the Nugent score, if doctors are still doing that. It’s a microscopic evaluation of who’s there in a vaginal swab. And Lactobacillus are there for a reason. It’s a niche that they inhabit. They produce organic acids, chiefly lactic acid, to keep that pH below four, and that’s a critical threshold. When the pH is elevated and becomes higher than a pH of four, you’re more prone to developing bacterial vaginosis.

And that’s commonly treated through antimicrobials, but there’s evidence that shows that even orally consumed probiotics can affect that vaginal microbiota so that it gets recolonized with these healthy bacteria, producing the organic acids and the antimicrobial substances so that you don’t have bacterial vaginosis or potentially, yeast infection. Those are things that can be prevented and potentially treated with co-administration or administration of the right probiotic bacteria.

James Maskell: So, what are those right probiotic bacteria for that particular issue?

Dr. Greg Leyer: So, when we look at a healthy vaginal microbiome, it’s dominated by a handful of species: L. gasseri, L. crispatus, L. reuteri, L. rhamnosus, you’ll find there. And so, to me, the right bacteria are those bacteria that have been shown through clinical studies to have a benefit. And two of the chief ones that have been tested, I would say, the world’s most documented combination, would be a combination of L. reuteri and L. rhamnosus. And they’ve been shown to, again, mitigate bacterial vaginosis—so reduce recurrent rates—enhance lactobacillus colonization in the healthy vaginal cavity, as well as reduce pH. They’ve also been shown to reduce yeast infections and even enhance treatment of antifungals.

So, when an antifungal is prescribed for a yeast infection, there’s a clinical study that shows if you co-administer these two probiotic strains with that antifungal, you enhance the effects. And you get 70% improvement over the standard classic treatment of avoiding yourself of a yeast infection. And then, by the way, you’re recolonizing the vagina with these healthy bacteria that’ll help maintain this homeostasis where you want it.

James Maskell: So, based on that, would you say that this could be like a new standard of care for the use of antifungals?

Dr. Greg Leyer: Based on this one study, I do. Of course, every scientist and researcher ends their research with more research needs to be done. I’d love to see this replicated, but the data is really compelling. And when you think about a 70% improvement over standard care, it’s hard to avoid that and turn your eye to that data. So, I would say that, yeah. The other thing we haven’t mentioned is: What are the side effects of taking a probiotic? There really are none, compared to taking a pharmaceutical. People may have experienced mild digestive upset if they’re taking a super high-count probiotic, but it’s really nothing. The safety record is outstanding, so I think, when you think about risk-reward, there’s a pretty high likelihood of reward and a very low risk of administering probiotics.

James Maskell: Are there self-optimization structures there? Where if you take too much, you can bring it back down to normal—or if you take too little. Is there a system that’s working in the background to create sort of an optimum?

Dr. Greg Leyer: The way I’m interpreting your question is more of: Is there kind of a rate of limiting return in how much you take? Yeah, and I would say that that’s probably an area that we need to do more. There’s not a lot of dose-ranging studies. There’s a handful, but I can think of a few of whom I’ve been involved with, more on the gastrointestinal side, whereby we see, in general, better clinical benefits the higher you go in dose. But in many cases, doses of a billion or two billion have shown clinical efficacy and meaningful results, not just statistical differences.

James Maskell: What do you think of the thesis that, “Well, if one billion’s good, then 10 billion must be 10 times as good?”

Dr. Greg Leyer: Yeah, I mean. Like what I just mentioned, I have some evidence in my back pocket that I can say, “Well, there might be something to it.” I always lean on: What does the data say? And is there really a benefit? For example, is 10 billion going to be better for a vaginal product versus one billion? I don’t know. I mean, have you shown it in a clinical study to be beneficial? I would say, “What does the clinical study…? What’s the efficacious dose that’s been proven?” Let’s go with that. I think, in different parts of the world, you get into a numbers game where more is better and, in some cases, maybe you could make the argument, but I don’t think it’s a universal, “Yes, that’s true.” I would lean on the evidence, basically, is what I’m saying.

James Maskell: So, where do you see this evidence arising from? You said there was one new study a day. Is the vaginal microbiome getting attention compared to other areas? In terms of the types of clinical conditions that you’re seeing success for, how important would you say that this… Are there systemic factors that relate to the health of the vagina generally?

Dr. Greg Leyer: Yeah, and I think the whole topic of women’s health is hugely impactful in terms of the research community. So, there’s clearly people that are experts in vaginal microbiome studies. That’s continuing on. There’s a lot of interest in: Are there similarities and differences depending on what ethnicity, or what geography you’re looking at? Will these probiotics be equally efficacious around the world? We’ve done a fair amount of studies to show that we think yes is the answer, that it’s effective independent of the host’s ethnicity or geography.

However, we do see differences in microbiome composition based on where you live and what you eat. That’s a key driver of who’s there. It’s what your diet is. It kind of starts there. It starts with nutritional interventions, making sure that you’re eating the right things. Most people in the Western world, I would say, probably aren’t eating the most diverse diet, full of fibers, et cetera. So, probiotics is a nice insurance policy to ensure that you’re getting the right type of bacteria that your body frankly expects to see and your immune system expects to see.

James Maskell: Yeah. When I looked into sort of how to get the best probiotic mixture and strains in the body, the topic of forest bathing would come up or being in nature because, in nature, you’d have a much wider variety. I would imagine that in this situation, because you don’t want the wide variety, probiotics might be, at least theoretically, a much more stable, clear way of creating the ecosystem that you’re looking for.

Dr. Greg Leyer: In our world, we deal with very defined fermentations producing the singular organism that we want to produce, and that’s the organism that we test, so it’s clean. I understand the concept of forest bathing, as you call it, or getting back to nature and indoctrinating yourself with normal bacteria, and I think there’s value in that, of course. There is data that shows epidemiological data that talks about, depending on if you’ve got a sibling or a pet or you grow in an urban environment versus a rural environment, you’re prone to develop certain conditions, mainly immunological conditions. This natural exposure is important, but when we’re trying to treat or mitigate or restore a very particular microbiome, I, again, lean on: What does the data say? I’d rather trust a defined composition that’s been studied in clinical trials versus something that’s not.

James Maskell: Absolutely. Well, look, let’s just, I guess, bring it all back. So, you mentioned the vaginal microbiome is not as varied. You want to have fewer strains. You mentioned L. rhamnosus; you mentioned L. reuteri. As clinicians who want to start using this with maybe their women patients that are suffering from bacterial vaginosis, yeast infections, et cetera: How would you take it? And how long would someone have to use them to see clinical results?

Dr. Greg Leyer: So, again, I will lean on the science, and we’ve seen results as quick as 14 days. So, when we’re running clinical studies, typically the outcomes we’re looking at is two, four, six, eight weeks long, but there are studies that show changes in microbiome and some clinically relevant outcomes as soon as two weeks after administration. Remember, these are typically orally consumed, so they need to reestablish in the right niche, and then produce… This takes a little bit of time. You’re not hitting it with an atomic bomb of a pharmaceutical. But two weeks, I think, is the soonest that we’ve tested as an endpoint in a clinical study.

James Maskell: Interesting. Okay. And I guess, following on from that, where do you see the research going next? What’s your research coming up? And what do you think that we’ll learn in the next couple years that you’re working on right now?

Dr. Greg Leyer: We’re continuing on studying a healthy vaginal microbiome and how do we impact that. What effects can we have? What changes? Now that microbiome tools are more and more sophisticated, we’re looking at who’s there, who’s not, how much of an impact do we have when we consume these strains orally in the vaginal microbiome. But even upstream of that, we’ve got some really fascinating research that’s looking at seeding infants, so looking at healthy moms, healthy, pregnant moms. What does probiotic consumption do to their immune system to how does it seed the baby? What impact does that have on the baby in the first few months of life and carrying on?

So, there’s a ton of data in just generally women’s health—from pre- to post-menopausal to pregnant mom—that’s happening with probiotics right now that we’re excited about. And I could talk to you a lot more about other research that we’re doing in the probiotics space, but, as specific to women’s health, those are the areas that we’re looking at.

James Maskell: Yeah, so fascinating, because I’ve actually seen research—and I’m sure you know about this more than anyone—but even a C-section birth, which I was, there’s some data suggests that you can’t catch up. It’s like if you miss the opportunity to go through the vaginal canal, even if you have a similar kind of environment growing up, you’re always a little bit behind with the microbiome composition of the baby. And so, studying the vaginal microbiome, like all women’s health, has this sort of exponential health effect or dysfunction effect because of the childbearing and then the health of the infants and then those generations of health going through. There’s really sort of like an exponential effect to women’s health and women’s reproductive health.

Dr. Greg Leyer: Yeah. And obviously, you turned out fantastically, being a C-section baby. However, it is a really interesting area of study, looking at the effects outward years. We’re getting some really surprising information from that. In some parts of the world, it’s more standard practice. If you’re going through a C-section, they’ll actually do vaginal swabs from the mom and bathe the baby, so it gets that contact. We know there’s changes, physiologically, in the mom preparing for childbirth. There’s microbiome compositional changes in the vagina, preparing for that delivery, to seed this baby in this kind of imprintable window that we call the first thousand days.

But that’s a fascinating area of study. We’ve got some data that just came out of a large study in Denmark that we completed that we will be communicating on shortly. It’s in the area. We’re just doing data crunching now but looking at the difference of directly seeding the infant versus seeding the mom first. So, fascinating stuff.

James Maskell: Yeah. I guess, with all the growth of probiotics and all the marketing and all the places, obviously, it’s been driven by consumers who want it, and then doctors are hearing about it, and there’s all this great research. Do you have any input or thoughts or opinion on why simple interventions like this aren’t making it into standard of care yet, and why it’s so slow to catch up?

Dr. Greg Leyer: It’s a good question. I’d probably turn it back to you to get your input, but I’ll give you my input. I think, as you know, this is not part of classical training, so maybe doctors would be a little bit more skeptical of something that’s not gone through a pharmaceutical development program. I think that might be a part of it. I think, many times, physicians will look at meta-analyses. Meta-analyses and probiotics are raft with some just inherent biases whereby there might be products that are in and studies that are in a meta-analysis that have no business being in there because it was underdosed, it was the wrong subject population. And it might give the meta-analysis more of a questionable score versus, “Hey, probiotics in general are good.”

And then, the use of the term probiotics has almost been genericized such that not every strain is going to do what this strain in this study did. So, I think, focusing on finding efficacious products that have been tested clinically to show a benefit will go a long way. You can’t just loop it together and say antibiotics are for everything. It’s not. Probiotics would be the same thing. There’s, in many cases, strain specificity. And so, we need to really be clear about what strains for what benefit, in my opinion.

James Maskell: Yeah. Well, I guess I would just say part of the reason why this is called the Evolution of Medicine is because we look at evolutionary concepts inside medicine, and, I think, maybe it’s not always best to be up on the very latest things because you want things to prove out over a period of time. But I would also say that a healthy microbiome is something that has stood the test of time, and this has been a feature of healthy humans for millennia. And it’s actually our current environment that’s very unhealthy and unusual. And so, ultimately, coming back to historical norms with regard to our internal microbiome is a healthy way to look at things. I’m grateful that there are tools that can get us back to where we need to be, and so, I’m grateful for you coming on to the podcast to share. Never a topic that we’ve talked about before.

I think this is critical, whether you’re in primary care, functional medicine, integrative medicine, lifestyle medicine. The majority of patients who come to your offices are women. The majority of clinicians are women here, so this is really critical. And it seems like this is a very easy way to evolve the standard of care. We’ve done quite a lot of stuff in the last few years on, let’s say, the pharmacy profession because there’s a new generation of pharmacists that recognize that there are downstream effects of the use of medication that aren’t being accounted for with regard to nutrition and so forth. And this, to me, seems like a similar kind of category.

If you’re going to use the antifungal, let’s use a probiotic to get the function back and to get the balance and the ecosystem back. Makes a lot of sense. So, Doc, thanks so much for agreeing to be part of the podcast. I learned a lot, and I think anyone who’s listening learned a lot as well. And we’ll put links to some of your research in the show notes, and thanks so much for tuning in. This is the Evolution of Medicine podcast. We’ve been talking about the vaginal microbiome with Dr. Greg Leyer. You can find out more about him, his work, his research, and some of the upcoming research he mentioned in the show notes. So, thanks so much for tuning in, and we’ll see you next time.

Thanks for listening to the evolution of medicine podcast. Please share this with colleagues who need to hear it. Thanks so much to our sponsors, the Lifestyle Matrix Resource Center. This podcast is really possible because of them. Please visit goevomed.com/lmrc to find out more about their clinical tools like the group visit toolkit. That’s goevomed.com/lmrc. Thanks so much for listening and we’ll see you next time.


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