Episode 09: Women Have A Whole Separate Microbiome That No One Talks About

Hello and welcome to The Better Biome Podcast, where we explore the universe within.

We're your hosts, Dr. Nicole Beurkens —

And Kiran Krishnan.

And on today's show, we're talking with Dr. Jacques Ravel about the vaginal microbiome and how it plays a key role in women's health. Dr. Jacques Ravel is a professor in the Department of Microbiology and Immunology, and the Associate Director for Genomics at The Institute for Genome Sciences, University of Maryland, School of Medicine in Baltimore Maryland. Over the past 15 years, he has developed a research program focused on applying modern genomic technologies and ecological principles to characterize the role and dynamics of the microbial communities inhabiting the human body in health and disease and better define the interactions between the host, the microbes and the environment that drives these ecological systems. Specifically, he is interested in the role of the vaginal microbiome in women's health in order to develop improved strategies to manage gynecological and obstetrics conditions. He has published over 225 peer-reviewed publications and has attracted grant income of more than $30 million. His work is currently being translated by developing novel live microbiome-based biotherapeutic formulations targeted to restore vaginal health, treat conditions such as bacterial vaginosis, urinary tract infections and improved fertility. His work earned him to be elected to the fellowship of the American Academy of Microbiology, and in 2015, he was awarded the Blaise Pascal international research chair. He is the founder and editor-in-chief of the journal Microbiome. He joined the Institute for Genome Sciences at The University of Maryland Medical School in 2007 as an associate professor. Welcome to the show, Dr. Ravel.

Hello, a pleasure to meet you.

Super-impressive bio. I'm reading that going "Wow! This is incredible!"

I haven't done anything with my life! What's going on! 200 published papers, over 200! Now, it's important for our audience, many of the people within the audience have never published a paper, so they don't really understand what it takes for publishing even a single research paper. And it's important to know that these are in peer-reviewed journals, right? So that's an important definition for our audience. That means you're doing research work, very high level research work. And then when you put together the culmination of your research work in a report, in a paper, then you're sending it out to your peers, whose job is to criticize it and find holes in your research, correct?

Absolutely, that's exactly the process. They give us, sometimes, very helpful comments and we have to go back and modify the paper, do more experiments and we modify the paper and submit it back to them. If they approve the work, then it gets published and people can read it.

Yeah, and you've done that over 200 times. That's what's so important for people to understand is that there are people that are health "experts" in the blogosphere on the internet and so on. There are people that write about health all the time, but then there is a whole other class of researchers that are doing it at the research level, that are being scrutinized by their own peers who are experts in the field. That's a whole other level of validation for the work. So at The Better Biome podcast, one of our focuses is trying to speak to as many people like yourself you are pushing and doing the cutting edge research. So it's really exciting to have you here, so thank you so much for joining us.

Yeah, absolutely.

So I'm really curious because you have had a career doing research in lots of different areas. How did you focus on the vaginal microbiome? And I Want to get into what that is and why that's important, but I'm curious about the evolution of your professional work that you came to be doing this type of specific research.

How did the vaginas call you?

How did that happen!

Do you have another hour? So I did my PhD in Microbiology, but in Environmental Microbiology, and it was really about the ecology of microbes that live in the ocean. That's how I started. I worked with somebody named Rita Colwell who is a very famous scientist who actually studies pathogens that live in the ocean like vibrio cholerae that gives cholera. So that's what I worked on with her, but it had a very heavy ecology slant. Then I decided that just like post after your PhD, you deal with a postdoctoral fellowship, and I needed to combine a little more expertise, put more tools in my bag, and so I decided to do postdoc in chemistry. During that post-doc, I started working on bacteria that makes antibiotics and trying to figure out what genes are making those antibiotics, because if you can figure out what they do, you can take them out and you can make more outside those bacteria. And that led me to start doing, understanding and learning about genomics, bioinformatics, which means understanding the genome of those bacteria, their genes, and using computers to analyze the data.

So I was at Johns Hopkins University doing this, and then that led me straight to one of the most prestigious institutes at the time, which was The Institute for Genomic Research. That was the institute where Craig Venter, the scientist who actually sequenced the first human genome, before sequencing the human genome. Actually, his own human genome. Actually sequenced the first bacteria. The first genome of a bacteria.

Which bacteria was it?

That was haemophilus influenzae and it was in 1995, it was published. So I joined this institute where basically, that's the pioneer for genomics. At the time, they were basically the only one in the US doing this kind of high-level genomic studies. So I got a training there that was just outstanding and I stayed there until 2007, so for about 7 years, and then I moved to The University of Maryland in 2007.

However, I still haven't answered your question, which is how I got to study the vaginal microbiome. So when I was at TIGR, I was studying bacterial genomes. And so bacteria, if you think about a biome or microbiome, bacteria is one component. One of millions of organisms that live in a biome.

So at the time, we were studying one of those at the time. We sequenced the genome of one bacteria, and we analyzed that genome. Then we started sequencing, when we realized it was just not enough to understand the ecology, what this bacteria is doing, in vivo, in the environment and so on. So we needed to sequence multiples of those so we can compare them and to see how they do things differently in one person versus another. And then, the methodology was there, but it was still not enough. We wanted to do more, so we started to do what's called metagenomics, which is really the infancy, the birth of microbiome studies, true microbiome studies, where we start sequencing all the genomes of all the bacteria that are in a biome, okay? And the first thing we did was study the gut, of course, because everybody was interested in the gut. The paper was published, I think in 2003 or so. And when you read the paper, at the time, I think we stretched the technology and the paper was interesting but it left an aftertaste, like what's next? There's something missing. It's not in-depth enough, and it was simply because the gut is too complex and the technology that we had was not accessing that complexity, so we were scraping the surface.

However, in 2004 I met a scientist named Larry Forney, who is at the University of Idaho, and he had started to study the vaginal microbiome. I invited him to give a talk at TIGR and we clicked right away. Then I realized that the vagina was the environment that we could study with the tool that we had at the time, the technology. The complexity is a lot less than what you see in the gut, and so the technology was very well-adapted to do this. So we can actually understand what's happening in that environment using the technology we had. We could understand, we could recreate all the genomes of the different bacteria that are present and see what they're doing within each other, how they interact with the host and so on. So that's how in 2004, I really jumped into studying the vaginal microbiome, because we were able to match the technology with the environment.

With the right community. So you mentioned that the gut microbiome is far more complex than the vaginal microbiome. We, at The Better Biome podcast will end up talking about the gut microbiome a lot because it's kind of a central command center for a lot of different things. One of the things we know is that diversity is good in the gut microbiome, but it might not be a good thing in the vaginal microbiome. So can you describe the differences between the gut and the vaginal microbiome? For example, how many different species can exist in the gut microbiome versus the vaginal microbiome, and do we want to see really high diversity in the vaginal microbiome?

Okay, so I think those are very technical terms, and we have to be careful when we use the term diversity, because diversity means a lot of different things. But you can have a lot of different things, but they're not balanced the same way. So you can still have a million different people that look different, but most of them are one type, and all the rest is made up by that tiny, tiny portion. That's what's happening in the vagina. In the gut, you have all those millions represented in about equal parts, if you want. So it appears you have a lot of diversity, but in reality you have almost the same diversity in the vagina, but we just don't see it because it represents a very small proportion of all the bacteria that are present in a vagina.

So the keyword is uniformity…

Yeah, we call it evenness. So the gut is more even, while the vagina is less even.

Let's back up a little bit because for many of our listeners, this is probably the first time that they're even hearing the term "Vaginal Microbiome". You probably get that a lot. Like, "This is what I study." And people go, "Really?"

"There is bacteria in a vagina?"

That's right! But I'd love for you to just give us an overview of when we say vaginal microbiome, what are we really talking about? What is the vaginal microbiome and then, is it the same for every woman?

Okay. That's a really good question. The vaginal microbiome is just like the gut, it's an assemblage of bacteria that live together…

That's a French word, right?

It's not an English word?

A collection!

They live together to perform a function that is beneficial. If it lives in the body, it's often beneficial to the host. In the vagina, for a long time, we've known because there have been a lot of microbiologists studying a bunch of different body sites, and the vagina was one of them. And since the late 1800, we have known that there was bacteria — at the time, they didn't call them that, but there was a bacteria named Lactobacillus that were present in the vagina. When those were present, things seemed to go well, and when they were absent, things didn't really go well. So there was this idea already that there was good bacteria and bad bacteria living in the vagina. So now when we are going forward, and when we start looking at the vaginal microbiome using molecular tools, we can be a lot lactobacillus more precise than saying lactobacillus and other bacteria, because we're not just looking at the microscope, and they don't have a little sign that says their name. So with molecular methods, we can actually detail and survey, make a list of all the bacteria that are present in a vagina. So it is true that lactobacillus, as it's called a genus, it's like a family of bacteria, is dominant, and is present in most women, in their vagina. However, there are also women that never have lactobacillus.

And still are healthy?

And still are apparently healthy. So healthy is kind of a term that is very hard to define. We don't know what health means. We don't know what normal means. But we can talk about optimal. So are you optimally protected, for example, verses less optimally protected? So when we start using molecular methods, we can actually, if you want, group women in five different types of microbiota, which was fascinating to us, because it's very hard to do in other environments. And four of those different types are dominated by one species of lactobacillus. So for example, those four are lactobacillus crispatus, lactobacillus iners, lactobacillus gasseri, lactobacillus jensenii. Lactobacillus is a very well-known bacteria, and if you eat yoghurt, it's in your yoghurt. However, it's not those four species. It's a different species that you find in milk and other dairies, and that's what makes your yoghurt, so it's very different. But the same family of bacteria. And what they have, they have a characteristic that's within all those species, all those different lactobacillus, they produce lactic acid. So they're called lactic acid producing bacteria. That lactic acid, if you remember your chemistry in college, lactic acid is a very potent acidifier. It has a pKa of about 3.24, so it can bring the pH down very low.

What they do, those bacteria, they acidify the vagina and you don't really know, but the pH of the vagina is about 3.6-4, so it's very acidic. When you think about acidity, obviously, you think about protection. We pickle things so they don't rot, we do things, I guess, we bring the pH down. So that's exactly what those bacteria do in the vaginal environment. However, we have that group of women, in America, it's about 25-30% of women that don't have lactobacillus. Some of those women are those that — if they're not sick, meaning if they don't have symptoms, if they don't need to see a doctor. We're going to put those women aside, but there are women that don't have those symptoms but still don't have lactobacillus. So there is still a possibility in the vaginal microbiome to not have lactobacillus and still be perfectly fine. However, those that have an acidified environment are those that you would call very well-protected. And those that don't, they are at a higher risk of potential adverse outcomes. Some of those outcomes are preventable, for example, sexually transmitted diseases, including HIV, those kinds of things where you have to do something, you have to step out.

Like a yeast infection or something?

Yeast infection is a little special.

Well get to the yeast infection!

But there are some diseases that you can acquire, some infectious diseases that you can actually prevent the acquisition of. For those particular things, they have a higher risk, while those that have lactobacillus don't. However, some of those women can also be at increased risk of other things, like problems with pregnancy, prematurity, sometimes they can have early abortion of fetus. So there are problems that can be linked to not having lactobacillus. While we think that those women are basically, what I call them, "Normal" but with an increased risk, there are times where we might want to do something about it and maybe convert them, if you want, to lactobacillus-dominated vaginal microbiota so they can carry their pregnancy at times. So they can do those kinds of things without any problem.

Bring down the risk.

Exactly. But basically, the vaginal microbiota, there are five types, four of them are dominated by lactobacillus, one of those four species. And one of them is not and it's represented, it's more like the gut, this type is very diverse. So you can see it's diverse and very even, a lot more even than what you see in the others.

So where does this vaginal microbiota come from, then?

Oh that's the million dollar question. There's actually very little work in this, because I think it's very difficult. There are some studies now that tend to indicate, obviously, the hypothesis is that it's coming from the mom when a baby girl is born through the vaginal canal, and that that's the time they transfer the microbes, and those microbes can colonize the baby girl. However, there are a lot of c-sections. So what happens when you are born through c-sections? You don't get a vaginal microbiota? Well that's not true. When you look at women who we know were born by c-section, most of them have lactobacillus. So there's another source of lactobacillus, and if we did a study in Brazil, recently, where the rate of c-section is close to 80%, so you would say — the vaginal microbiome has not disappeared in Brazil, it's still present, the environment, I think is highly selective for lactobacillus, so when there's an opportunity for those lactobacillus to colonize, they'll be there. So we think that there are other life events within the household, changing diapers, I mean there are a lot of opportunities for those microbes. You don't need a lot of them to go from moms to daughters or from something else to the daughter. It's still very unclear exactly where a woman gets her vaginal microbiota, there are hypotheses that are being generated right now.

That's really interesting. Now, a two-part question then, is there any evidence or any mechanism by which you can think of where gut-based bacteria end up in the vaginal canal, and/or we see very close proximity to the vagina is the anal cavity, and fecal bacteria may contain lactobacilli. Is there contamination? Or in that case, we would call them positive inoculation there from either of those routes?

Absolutely. There is a lot of work on this, showing that you can find vaginal bacteria in the rectum or in stool. But this is not the final proof that vaginal bacteria live in the gut and actually colonize. When people keep thinking about this question, they're always thinking in one direction: The route is always the rectum to the vagina, it's never the vagina to the rectum. If you think about it, it's just as likely, if not more likely to go the other way. So if you find vaginal bacteria in the rectum or in stool, it's entirely possible that it's actually colonization from the vagina to the rectum. However, it's entirely possible to see bacteria going from the rectum. There were known lactobacillus that go into the vagina. Often those don't last very long because the pH is too low. The protection, that protective barrier that they create, actually protects from those colonizations.

So the things that you're talking about are really not only fascinating but really important. As a woman, I'm listening to you, thinking I've never heard this information before. There are so many roles then that this plays, that the vaginal microbiome plays in many aspects of women's health. You mentioned not only things like sexually transmitted infections and things like that. But can you expand on that and just talk a bit more about how the composition of the vaginal microbiome impacts a woman's overall health?

Overall health, that's in different ways, every time. So if you think about different conditions, from as you mentioned, sexually transmitted infections, fecundity — so, getting pregnant: Is that important? Implantation of the egg. Is that important? Yes it is. UTI, you mentioned yeast infection, it's still very unclear because actually when we do those studies with yeast infections, it's almost counter to what you think. It's more often associated with the presence of lactobacillus than none. It turns out that yeast actually like lactic acid, they like low pH environments. So there's almost like a counterintuitive association here. But it's involved in all those aspects of life. Having problems is also a major issue for your quality of life. In our study, we deal with women who have those problems, and it is devastating. Those who don't experience it, don't see it, don't understand it, but it's a major, major issue. It's associated with burning, itching, and odor. Women who have odor just live a terrible life. People can smell it, and they don't know what to do about it. And doctors almost are left without options as well. So it's a big problem. The vaginal microbiome plays a role in almost all those aspects of life.

What about something that I've learned about, that is vaginal dryness in perimenopausal and postmenopausal women that eventually makes intercourse very painful and really not plausible. Is that something that has to do with the vaginal microbiome?

So it's kind of a dual component here. So maybe we can step back a little bit. There is something very interesting about the vaginal microbiota, as opposed to the gut, is that it goes through major transition throughout a woman's life. So at birth, actually, the vaginal microbiota, soon after birth, gets colonized very quickly. Often, lactobacillus makes its way through. We can see it in baby girls who are less than about four weeks old. The reason we see it is because a baby girl has estrogen — her mom, when you're pregnant, you are basically in a hyperestrogenic state. You produce a lot of estrogen. It goes up until you deliver, where it just crashes. So the baby girl has been sharing blood, basically with her mom and has estrogen in her own blood, but she is not making estrogen. So it's enough to basically take the vagina and turn the lining of the vagina into a perfect environment for lactobacillus because what happens is that there are sugars that are in the superficial lining of the vaginal, and lactobacillus love those sugars, that allows them to thrive in the environment and outcompete anybody. So they can colonize when you have estrogen. But of course, four weeks later, there is no more estrogen, and it's true. From about 4 weeks to 8,9 before puberty starts, you barely see lactobacillus. It's there, but it's in very low quantity. It's almost like surviving. And then at puberty, estrogen goes up and those girls start being recolonized by lactobacillus if they had lactobacillus early on, and they're going to be like this their entire life.

What happens is that at menopause, we have the opposite, and that's one of the reasons you have vaginal dryness, you have estrogen going down, and it goes down at different rates in every woman. So that transition is different in every woman, and when you start losing estrogen, you lose this sugar in the vaginal epithelium, and that's a big problem, and that's what creates often this vaginal dryness. That's why a hormonal replacement therapy basically deals with those conditions. They basically refurbish the vagina with those sugars and mucous and everything. That makes it more lubricated, and so on. So the problem is that it's associated with the loss of lactobacillus, vaginal dryness because you also lose estrogen. So the two go hand-in-hand. The big challenge is how do you restore lactobacillus and the moisture that you had, the lubrication. That's the big challenge in menopause.

I'm curious because you know — I have four children, so pregnancies and all of that. I'm thinking about all the processes and check ups and things that are done to women, just even in annual exams, but also during pregnancy, and I am just curious: Do you see an impact that interventions and things like checkups and ultrasounds — I'm thinking of lubricants that are used when they do intravaginal ultrasounds and things like that: Have you done any work to know what kind of impact that has on a woman's vaginal microbiome?

Absolutely. So we have an ongoing study right now in collaboration with Dr. Rebecca Brotman at the University of Maryland School of Medicine. Basically, we are using ultrasound as a model to deliver lubricant to the vagina and looking at the impact of lubricant on the vaginal microbiota, the epithelium and so on. This is a really interesting thing because we monitor those women, so we capture them when they make their appointment for the ultrasound. So we have longitudinal information, and then they start sampling themselves everyday until the appointment where they receive the ultrasound, and then they continue to sample everyday. so we have a very high resolution picture of what's happening, what they are before the ultrasound and what happens after. So one thing is very important when you think of lubricant, it's that a lot of people use lubricant for intercourse, it's used in medicine, and there are many different kinds. They are all different. They all claim they have different properties, but the hallmark of most of them is hypertonicity. They are very hypertonic, that's a big problem because what happens is it basically dries the cells. They have to put some of those chemicals that help that lubrication, but by doing this, you also basically empty the cells of their, if you want, their water. The water they have inside. That creates major problems, lesions and things like that. Of course, if we dry the cells, we are going to dry the only source of nutrients that the bacteria in the vagina have. So when you have lubricant of that kind, you can have a major effect on the vaginal microbiota. That's not the only thing that those lubricants do. Most lubricants, especially in medicine, contain antimicrobial agents, so things to kill bacteria. Chlorhexidine is often found in those medical lubricants. This is the double whack on the bacteria.

But what's very interesting is that not every woman is affected by the application of lubricant, and I think this is a very important aspect because it's true for many different things. We know that there are all those types, I told you, of different microbiota. Within those types, some of those women with a certain type tend to be more affected than others. So by doing all those studies, we started to learn, we think at the beginning, "Oh, you have lactobacillus, you're perfectly fine." We started to realize, well, not all lactobacillus are created equal. I studied bacteria and their genome, and I tell you: This is something we've known for a long time. You have two bacteria, they might have the same name but they might do things completely differently. One very famous one is E. coli. We have E. coli that's going to make you sick and maybe kill you, and we have E. coli that you have in your gut and you need to have. But they are both named E. coli.

And genetically, there may be just minute differences. We are talking about just a few percentage points different in their DNA.

Exactly, so it's very important to understand those differences. So we know those lactobacillus are not created equal. By gathering all this information, we can actually start thinking a little more about how we can restore a protective, resistant, resilient vaginal microbiota. The study of lubricants is an interesting one. There is a public health aspect to it, but there is also a scientific aspect to it that we would like to leverage to basically develop better products, better new strategies for intervention.

One of the things, I'm guessing a lot of our audiences are already wondering right now is understanding what would be relatively a sensitive community of bacteria within the vaginal microbiome, it's certainly more sensitive in some women than others like you just described, and this important dynamic community that controls so many aspects of her overall health: With that in mind, what are some of the things that people are doing in day to day life that seem to be hurting the vaginal microbiome?

So there are many different aspects of life that could potentially affect the vaginal microbiota. One of them, which is interesting and when we do the epidemiology, tend to actually come back and be more — we find this in those surveys a lot more often is douching. Vaginal douching. If you go to CVS or those drugstores, you see them all. They have different flavors, different scents and so on.

Very nice packaging! Makes it look wonderful!

And women tend to use them. I think those are actually one of the worst things you can do to the vagina. You're basically washing your vagina with chemicals. It might smell good for a few hours or a day or so, but what's going to happen after this is worse than the reason you actually started it.

So it's definitely recommended not to do this. Obviously, one big aspect that a lot of people don't think about is smoking. Smoking has a major impact on the vaginal microbiota. Dysbiosis of the vaginal microbiota, the condition we call bacterial vaginosis is actually associated with smoking. There is a metabolite of nicotine and tar and so on, that when you smoke within your lungs and your blood, basically also ends up in your vagina. Those metabolites, those chemicals are not good for your bacteria. The other aspect is also diet. This one is a little — not as well understood as we would like, but there is also a strong association between dysbiosis of the vagina, so problems, not having lactobacillus, with obesity. Because obesity also could be linked to some aspect of your diet, there are now studies looking at that correlation. So diet leads to potentially a more proinflammatory — a poor diet can lead to more proinflammatory high permeability of your intestinal lining. Whatever gets through your intestine, whether it's protein immune markers or anything that's in your gut that goes in your blood could end up in your vagina. That triggers the immune response in the vagina, just like it's triggered in your gut at the end of the day, it's also triggered in the vagina. A pro-inflammatory environment in the vagina is also not beneficial. Lactobacillus do not like those environments. That brings a very interesting aspect because there are products you can buy here in America that are claiming to treat vaginal disorder through products that you actually ingest. So it's bacteria, probiotics. In America, they can be called probiotic, in Europe, they can't do it. But it's called probiotic here, and they're all for women's health. And it's a very interesting things, because very rarely, just like you mentioned earlier that bacteria can go from the gut to the vagina, while you're putting billions of bacteria, of lactobacillus, often not even vaginal lactobacillus, but you put billions of lactobacillus, and they almost never end up in your vagina. If they do, they never stay there very long.

However, there are small, but published peer-reviewed clinical studies that show that sometimes they can have an effect. Maybe a 20% to 30% effect. It's kind of an interesting finding because you're not colonizing but you're taking it orally. I think that supports this fact that if you have a healthy gut, you can have a healthy vagina. So when we talk so often of gut-brain access, I think there is also a gut-vagina access that needs to be studied.

One of the parts of the body that I'm most fascinated by is the mucosal system. We've got more mucosal surface than anything else in our body. There are things I've read about called the singular mucosal theory where there's a singular response in the mucosa throughout the body, or an impact on one part of the mucosa can certainly impact another part of the mucosa, and of course the vaginal canal is full of mucosa, and the gut is a very complex and active mucosa. So maybe there is some correlation there between things that happen in the gut mucosa lining and the vaginal mucosa lining. Healthy gut, healthy vagina, may be even through that mechanism.

Absolutely. And certainly the immune system is playing a big role there. The cervix is actually a really important immune organ that is not seen as an immune organ, but it's a really important immune organ.

I'm curious, because you touched on douching being one of the worst things that you can do for your vaginal microbiome, I wonder, does that apply — just thinking from a practical standpoint for women who are listening, to other personal care products that we might use in that area of our bodies, for example, things like tampons that may have a lot of chemicals in them if they're not organic, or even body washes or sanitary pads or things like that. Can those things, the chemicals that might be present in those things impact the vaginal microbiome as well?

It's entirely possible, but there is very little, if not true scientific literature on this. There is actually a craze right now for those organic tampons, so there are people that are basically setting themselves up to study the impact of organic tampons on the vaginal microbiota, but it's very important. Tampons in the 80's, 90's were in big trouble because of toxic shock syndrome, so that was a big issue. And they found out simply that it was all about their absorbency. So they were too absorbent. And what happens by doing this, they basically do what lubricants do, the cells themselves get empty, and their liquid goes inside the tampon. That created lesions and that led to stuff being able to infect. So it was simply because they were too absorbent. There are so many products on the market and those are cosmetic. They are not drugs, so they don't go through the same kind of regulatory pathway that you would go through with a drug that you will ingest, so it's sometimes very difficult to even select something. What's appropriate for you might not be appropriate for somebody else. It's often by trial and error that women settle on their way to do those things.

Speaking about ingesting things, what about oral antibiotics? If a woman is taking an antibiotic for a sinus infection or something else, does that have an impact on the vaginal microbiota?

So it's another area where there is very little inflammation. We have tons of data on the gut, but very little on the impact on the vaginal microbiota of antibiotics. We've done some studies, when we do those observational studies where we follow women daily for weeks, we can capture those events where they get sick and they have to take antibiotics, and it doesn't exclude them from staying in the study.

What we find is that there are antibiotics that can destroy the microbiota, but it's never a consistent effect. So it's a very personalized response, which makes a lot of sense because they have a microbiota that's theirs, even though they belong to one of those five groups, it's still very unique. And so you will respond to different antibiotics differently. And bacteria, some are more resistant than others. They develop ways to resist those antibiotics. Even beneficial bacteria do ultimately resist antibiotics. So that's one thing that we know, is that for example, because we study sexually transmitted infections, in the treatment of chlamydia, when somebody presents with chlamydia, they take one gram of azithromycin. It's one dose, you take one gram and you're done. That really heavy dose of azithromycin has a really detrimental effect on the vaginal microbiota. So we don't see that as much when women take azithromycin for respiratory infections. So a much smaller dose would be 250 grams, but they will take it for a longer period of time. So that effect of azithromycin for the treatment of chlamydia is actually a big problem. While it's needed — we have to get rid of chlamydia. We can't avoid it. Right now we don't have all the solutions, but we don't think about the effect it does on the microbiota and what it does to the susceptibility of being reinfected.

What that antibiotic does is cure chlamydia, which is exactly what we wanted to do, but it leaves a vaginal microbiota that's highly, highly susceptible to infection and that's a major problem. So we really need to think about strategies where we treat and then we restore. Just like we think about doing this in the gut. There are companies that are going out there to have antibiotics or a product that you can take to protect your gut while you take the antibiotics. We need to think about this also for other body sites, and the vagina should be included into those strategies.

I think that that's interesting, it's going to be my next question about how you see the type of research that you're doing on really specific things within the vaginal microbiome being translated into tools or strategies that can really positively impact women's health. What do you hope are some of the things that will come out of the reproach that you're doing that will positively impact women?

As a disclaimer, disclosure, I started recently a company that's called LUCA Biologics and I am a cofounder of it. Our goal is to leverage that science to develop what we call live medicine for women. But those will be actual drugs. One thing when you study, there are a lot of works on probiotics and for the gut and so on. A lot of time, when you look at the science, they think about the environment as just the microbiota and there is bacteria. They don't think about the environment those bacteria live in. That's where my ecology training in microbial training has been very useful because you can't just look at an environment having bacteria. There are chemicals, there is a host, that's us, that gives food — so there is food. That's present. Then the bacteria are taking this food and making it into something else that can be used for the next bacteria and so on. So it's really an ecological system, it's an ecosystem. Those bacteria live with each other. You can't just take one out and say "I'm going to give it to you and you'll be fine." That bacteria by itself is never going to survive, because it needs all its friends around to survive and make that network and live together. And that network doesn't survive if you don't give it the proper food, okay? Or even, if you don't favor it with giving it the proper chemical environment. You need to get a jumpstart. When you try to completely change an ecosystem, you have to disturb the one that's already present and favor the one that you want to put in. Without doing this, it's failure after failure.

Often, a diseased ecosystem is very strong. I mentioned earlier, in the vagina, those tend to have a lot of different bacteria. They're more diverse, and those bacteria are all very tightly working together. It's very difficult, if you kill one, somebody else is going to take that place and perform the exact same function that the other one was doing. So you need to create an environment that's not favorable for those, and favorable for those that you want to put in. So the work we're doing is not just studying the bacteria, it's studying the complete environment, and that's the distinction I make between microbiome, which is that environment, that ecosystem, and microbiota, which is literally the bacteria.

Studying the microbiome is very important. We study it from the bacteria, from the chemistry, from the food, the nutritional aspect of things. Then we can learn from this and create concoctions, formulations of all those different components. So when you put a bacteria in, all of a sudden the pH is right and that bacteria can work well. We know lactobacillus loves low pH. It doesn't do that well at higher pH. The other bacteria do. So if you can knock them down with slightly lower pH, they're not really too happy, but lactobacillus is very happy and starts growing. So we're learning from all this and basically making formulations that we are going to be testing in the fall, we're going to be starting the testing of some of those to try to restore a very healthy — you just don't want to restore, you also want to maintain it.

It changes a lot of the approach that we have of drugs. The way we think of drugs is you take it once and you're good. Even though it's changing because we have a lot of chronic diseases that people have to take drugs for on a daily basis, I think that also needs to be applied a little bit to the microbiome because we can't hope to restore something and we're done. Often it's on a slope and it's going down again, so you have to kind of reseed it and re-jumpstart it over and over again. It's not just what you make and what you're going to deliver as the drug. It's how you deliver it, how often you deliver it, how you maintain that ecosystem. Sometimes, after that, you don't need to provide the bacteria. You might just need to provide the food. That's all it takes, because the food is not provided by the host anymore. There are strategies like those, so by taking that science, we can make those pills and have them available for women. The big challenge is the distinction between drugs, for which you need a prescription, and something that you buy at the grocery store. We have probiotics. The problem is the science behind probiotics: For some of them it's super good, it's very strong. But consumers don't differentiate. They all say "Clinically Tested" but some have very strong scientific clinical evidence for efficacy, others don't. By going through the drug route, we kind of guarantee that the science is sound, it's been FDA-validated. That's why what I want to see is to take this, but take it through the drug. After that, I think access to those drugs is a big problem. The big advantage of those drugs is they are a lot cheaper than normal drugs, like chemical drugs. So they become affordable, so we could at some point bring them back into the grocery store. But they have to be a drug first before they can become over-the-counter.

And that's super exciting, that work that you're doing and that you've got the new entity, that you're spinning off on that. Clearly just from this conversation alone, it's clear that we do have a possible epidemic of dysfunctional vaginal microbiota that lead to all these other conditions. And what I love about what you just said, and the whole idea of The Better Biome podcast is we're trying to help people understand ecology, community structures, environment, all of these things that play a role, and there are multiple effectors of the ecology, like you said, it's not a single bacteria, it's not a single virus, it's not a single thing. It's about altering the environment so that the environment favors the balance or the health-promoting ecology. It's wonderful work that you're doing. We're honored to be able to talk to you about this.

We really just have one more question for you, for our listeners, really. If you were to think of one thing that you might recommend or suggest that listeners could start doing even right now or tomorrow to improve their biome. Their vaginal microbiome or their biome in any way, what would be something that you would think could be a helpful starting point, either for them to think about or an action that they can take?

Obviously I don't have that solution that is delivered directly to the vagina, but I truly believe that a healthy diet would help their microbiome. Not only their gut microbiome, but their vaginal microbiome.

And how would you define a healthy diet? What are some of the components of a healthy diet?

High in fiber, fruit, vegetables. Things like that. I think that it's been shown over and over again that it helps. Obviously there are conditions where you can't do that, but I think that would help.

So the more that women can move towards eating what we might think of as whole foods, unprocessed healthier foods that benefits their health overall, but specifically, also benefits their vaginal microbiome.

And there also are studies that show that the vaginal microbiome benefits from exercise as well. Again, we don't really know the mechanism or how, but it could be through…

So all those things that we're told to do anyway, for 100 different reasons, you've given us one more reason to eat better and exercise. Thank you so much for being here, this was a fascinating interview. We really appreciate it.

My pleasure.

Thank you, everyone, for joining us for today's episode of The Better Biome Podcast. Tune in next week to continue with us as we journey through the universe within.