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BackTable / OBGYN / Article
The Role of the Microbiome in Gynecological Disorders
Dana Schmitz • Aug 22, 2023 • 38 hits
Dr. Ian Fields, urogynecologist and assistant professor with OHSU School of Medicine in Portland, Oregon, highlights the human microbiome and how it plays a dynamic and multifaceted role in various medical conditions. A new perspective on the vaginal microbiome is presented, challenging the common misconception that all bacteria signify infection and emphasizing the delicacy of balance in this area. Unconventional approaches like fecal transplants for clostridium infections, the existence of a urinary microbiome, and the complex interplay between bacteria and conditions such as urinary incontinence and bacterial vaginosis highlight a broader understanding of the microbiome's intricate connections to human health.
This article features excerpts from the BackTable OBGYN Podcast. We’ve provided the highlight reel in this article, and you can listen to the full podcast below.
The BackTable OBGYN Brief
• Evidence from recent studies has shown that the bladder hosts a diverse bacterial community, even in healthy subjects, contrary to previous beliefs that the bladder was a sterile environment.
• Bacteria present does not always mean infection; there is a homeostatic balance within the vaginal microbiome.
• Recent research shows that specific bacterial genera in the bladder can affect the response to mid-urethral sling surgery.
• Acknowledging the urinary microbiome offers a paradigm shift in diagnosing and treating urological and gynecological conditions, potentially requiring updates in medical education and clinical practice.
• Disturbances within the microbiomes of the uterus and intraperitoneal cavity may be linked to disorders such as fibroids, endometriosis, and chronic pelvic pain.
Table of Contents
(1) The Impact of the Microbiome on Disease & Novel Treatments in Gynecology
(2) Challenging the Sterility Myth: The Urinary Microbiome's Role in Gynecological Disorders
(3) The Microbiome & Urinary Tract Disorders
(4) Uterine & Intraperitoneal Microbiomes in Female Reproductive Health
The Impact of the Microbiome on Disease & Novel Treatments in Gynecology
The microbiome in relation to gynecology and other disease processes is very complex. There is a common misconception that all bacteria signify infection, which highlights the necessity of understanding the delicate balance within the microbiome. Clostridium infections, for example, are often associated with antibiotic collateral damage in the gut. Fecal transplant, an unconventional treatment approach, aims to repopulate this damaged area with healthy bacteria to restore gut homeostasis.
[Dr. Mark Hoffman]
What are examples of situations where-- Because I think most people think bacteria means infection. There's some bacteria we don't want, let's get rid of bacteria. Especially in gynecology, if there's a discharge, give me antibiotics to treat it. Well, there's a lot of normal activity in the vagina. There's bacteria, fungus, if we hit one, the other can have an opportunity to overgrow.
That's one where we see the microbiome maybe more frequently in our clinics, but what are examples of some big situations where the microbiome can impact or be related to disease processes?
[Dr. Ian Fields]
I think one of the things that fascinated me the most when I was in medical school was studying and learning about clostridium infections in the gut. We hear about C. diff after antibiotics. There's a very large amount of work that was really done with the gut microbiome; is perhaps one of the most studied microbial niches.
C. diff happens typically after patients are treated with antibiotics for some other infection that antibiotics have some collateral damage elsewhere in the body. The gut is a big place that gets that collateral damage. At that point, you potentially develop this clostridium difficile infection.
I thought we treat it with antibiotics, but one of the other ways that we can treat this is by doing fecal transplants, which I thought was just the most out there thing that I learned. I was like, "Wait a second, you're telling me that they're taking stool from healthy people and placing it in somebody's gut?" I just thought that is so bizarre, but fascinating at the same time to me that somebody had thought about this.
[Dr. Mark Hoffman]
No, I think every time anyone hears that for the first time, there's always that like, "Oh, come on." Then people want to learn more about, "Wait, I'm sorry, did you say transplant? Who's the donor, who's got the best stool out there?"
[Dr. Ian Fields]
How do we decide that?
[Dr. Mark Hoffman]
We got to bring in this guy again because his patients are doing great. How does one maintain a kind of feces that is desirable for transplant? My goodness. This is a whole other thing that none of us know anything about. Clearly, there's a lot out there we don't know.
[Dr. Ian Fields]
Right. I think that that was something that blew my mind as a student that this is something that was happening.
[Dr. Mark Hoffman]
Was your basic science research in the microbiome or what was--
[Dr. Ian Fields]
It was not. I studied mechanisms of cell polarity and polarized epithelial cells with broad implications for renal cancers. I worked with kidney cell lines and did lots of like, "Okay, how do cells decide that they're going to grow in the way that they do?" Once we learn baseline, how they function, then we would knock out functions of certain proteins that we were studying to see how that had an impact on these mechanisms of how cells grow the way that they do.
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Challenging the Sterility Myth: The Urinary Microbiome's Role in Gynecological Disorders
The commonly held belief that urine and the bladder are sterile has been challenged in recent years, opening new avenues in understanding and treating gynecological and urological conditions. Groundbreaking studies conducted by Loyola University in 2012 and 2014 show that the urinary tract harbors its own microbiome, and an awareness of the urinary microbiome impacts the understanding of conditions such as bacterial vaginosis, urinary incontinence, and interstitial cystitis. The discovery of bacteria being present in the bladder of healthy patients has wide-reaching implications for clinicians.
[Dr. Mark Hoffman]
Not a direct line, but as an English major, I'm definitely thinking, "Okay, this, this is all way above my pay grade." Clearly an advanced level of understanding of cell biology, which allows you to be far more in tune with what's going on in the microbiome.
In gynecology, what do we know? What are the areas of work that's being done and what's the future hold for our better understanding of the microbiome?
[Dr. Ian Fields]
That is a great question. Most of the work in terms of what we see clinically as gynecologists, urogynecologist is the shift in homeostasis that happens with the healthy bacteria that live inside the vagina that lead to things like bacterial vaginosis. I think that's probably the most studied condition in terms of how it relates to the microbiome in our world, but as a urogynecologist, I have specific interest in urinary tract disorders like incontinence, both stress incontinence, urgency urinary incontinence, recurrent urinary tract infections and conditions like interstitial cystitis and painful bladder and all have implications in terms of studies that have linked alterations in the microbiome, in the bladder to those different conditions.
It's really funny because going back to this, a lot of this work about the urinary microbiome also came out of Loyola University, which just again, so interesting that my life has taken me down this path and I have so much crosstalk and interplay with the people that have done this research, although I have not worked on it there myself.
[Dr. Mark Hoffman]
In recurrent UTI, I was trying to think about in preparing for the show today, like things that I would've thought would be impacted by the microbiome within the urinary tract specifically, but pelvic organ prolapse-- Is that what you said? Or things like interstitial cystitis, which as a pelvic pain person, I see a lot.
The other conditions you're mentioning too, I wouldn't have thought the microbiome would play as much of a role. Can you talk about the ways that the microbiome could or does, or could potentially impact those different disease processes?
[Dr. Ian Fields]
We'll backtrack just a little bit here because the first thing we have to realize is we have to challenge this dogma that the urine or bladder is sterile.
[Dr. Mark Hoffman]
Yes. Lots of Twitter chatter, I think by some experts like you about whether or not people should be thinking it's sterile. I won't go any maybe further than that.
[Dr. Ian Fields]
Yes. There's a lot that you can get into on Twitter in terms of weird practices that they relate to medicine. This was like a hot topic, I want to say, a couple of months ago when Ashley Winter, who is a urologist, tweeted that urine was not sterile. You would've thought this is like flat earther territory again. People are just attacking her saying like, "This is so dumb. Of course, you're in a sterile, how would you get a bladder infection if urine is not sterile to begin with?" It takes so much of you to sit back and say, "This is potentially not worth my fight right now in this forum, specifically."
[Dr. Mark Hoffman]
"How much time do I have? How much energy do I have left-
[Dr. Ian Fields]
Correct.
[Dr. Mark Hoffman]
-for this conversation?" The answer is, probably not enough.
[Dr. Ian Fields]
Yes, most of the time the answer is not enough to engage. Although, I did jump in and participate here and there, I was like, "I don't really want to get into this and I don't really want to bring out the troll."
[Dr. Mark Hoffman]
Mute notifications.
[Dr. Ian Fields]
Yes, mute notifications on this thread. No more, please. She tweeted that urine was not sterile. I think we know this at this point in time. I think we have really good evidence and a lot of that work again, came out of work that was done by microbiologists immunologists at Loyola University; Alan Wolf and Paul Schreckenberger well as Linda Brubaker when she was at Loyola, had done all this work to really challenge this dogma that the bladder is a sterile environment, because the bladder was not included in the human microbiome project. The vagina was, but the bladder was not.
It's plausible. We as gynecologists know, and I think this is like such an interesting quote from Alan Wolf when he talks about the work that he's done, says, "It was ludicrous to me when I found out that medical students were learning that the bladder was sterile because the female urethra is just like a day trip for E. coli." It's really doesn't take much for-- It's three to four centimeters. E. coli is, of course, going to be able to climb in there. That's how we get these infections. That's how UTIs manifest is typically because of things like that, and E. coli motility.
He thought, "There's got to be a way that we can study the bladder and figure out whether or not urine is sterile." One of the first studies he did was looking at voided specimens, super pubic aspirate and urethral catheterized specimens to determine whether or not there was bacteria present.
He did this. Basically, you can do this through a series of sequencing what you know is there based on the bacteria that you would expect. You sequence what's called part of the 16S ribosomal RNA, there's like variable regions that are pretty consistent throughout like evolutionarily that you can find in sequence even if bacteria-- to see if bacteria are there. He essentially was able to show that, "Yes, there is a large community of bacteria that lives in the bladder in healthy patients and healthy subjects."
[Dr. Mark Hoffman]
It makes me think about, because I'm a big fan of science and space travel and those things; how do you know if you go to Mars if there's life if you've touched all this equipment and you send it there? That's a huge part of that whole science of studying whether or not there is evidence of life in places where we didn't expect it.
It sounds actually very similar because if you're going through a catheterized sample or going through the skin into the bladder, you could potentially be bringing things in. That's where you have to have people who know what they're doing, who understand what to expect and compare it, but I can see how it would be. That would be really challenging work to do, because to get into the bladder to see if there's bacteria, you were going through all these bacteria rich microbiomes to get there.
[Dr. Ian Fields]
That's why this midstream voided specimen that we use to figure out if a patient has a UTI is catching all of this skin from the vulva and the vagina, so we can't know for sure.
[Dr. Mark Hoffman]
I feel like every urine culture I get is–
[Dr. Ian Fields]
Polymicrobial.
[Dr. Mark Hoffman]
Polymicrobial.
[Dr. Ian Fields]
I feel like that's what you're going for, polymicrobial.
[Dr. Mark Hoffman]
Yes. Thank you.
[Dr. Ian Fields]
Polymicrobial.
[Dr. Mark Hoffman]
Polymicrobial. Yes. It's like–
[Dr. Ian Fields]
"What do I do with that?"
[Dr. Mark Hoffman]
Nothing is what I've been usually doing with it. It's everywhere. How do you know what's what? That sounds really challenging.
[Dr. Ian Fields]
It is. He then took that a step further, because you can say, "Okay, great you have presence of bacteria that are there based on these genetic sequencing that you've done. That means you could have dead bacteria that were anywhere. How do you know that these bacteria are alive and they're healthy?" He was like, "All right, well, let's just take this a step further."
He challenged the standard urine culture. Basically, took a cohort of patients who were healthy controls and patients with urinary incontinence and had their urine plated under standard aerobic conditions at 35 degrees Celsius, grew for 24 hours. Did it grow or did it not? Then took those same samples and grew them under a variety of different conditions, different culture mediums, anaerobic conditions, different temperatures, longer periods of time, and was able to show that over 90% of people who had been a part of this study, you could cultivate bacteria that way from the bladder, which was just this huge paradigm shift.
[Dr. Mark Hoffman]
Who's the one doing the work? Whose work you're referencing, and when was all this research done?
[Dr. Ian Fields]
This was done back in 2012 and 2014. This is the team at Loyola University, the two PIs on the study, Alan Wolf and Paul Schreckenberger.
[Dr. Mark Hoffman]
That's pretty recent, though.
[Dr. Ian Fields]
It is.
[Dr. Mark Hoffman]
In the scheme of medical research, things like basic stuff we know about the human body, 10 years is not that long.
[Dr. Ian Fields]
I remember being at the American Urogynecologic Society meeting at the time when these papers were presented, and my mind was blown. I was like, "This is so far beyond anything that I could comprehend as a student, as a resident." It just was mind-blowing to me.
[Dr. Mark Hoffman]
Was it taught in med school prior to this that urine was sterile? Was that like--
[Dr. Ian Fields]
I think so. [laughs]
[Dr. Mark Hoffman]
I'm like trying to be cool. I know stuff, I'm like, "Maybe thought urine was sterile too." I've been out of training for 10 years and I don't deal with the urinary tract. At least I try not to deal with it very often in my job.
[Dr. Ian Fields]
If we can avoid it, yes. [laughs]
[Dr. Mark Hoffman]
If we can avoid it, right. I'm trying to sound like I know what I'm talking about. I feel like that's what we were taught. It was sterile.
[Dr. Ian Fields]
I believe so. Despite me being at Loyola, I'm pretty sure that's what I was taught. Alan Wolfe was one of my microbiology teachers, so I hope he doesn't come after me after this. I'm pretty sure at that. I was in medical school around 2009, 2010 is when I would've been learning.
[Dr. Mark Hoffman]
Well, if you used a textbook, it was probably written in the '80s, anyway. The thing is, this information typically happens or progresses pretty slowly or at least it's delivered pretty slowly. This is a big thing to think about. All the things that we don't know about, that you're talking about, especially interstitial cystitis or painful platter syndrome that we see a lot in our endometriosis patients, recurrent UTIs. At some point you just go, "I don't know what to do with that."
Can you talk a little bit about specific diseases? We had to back up. Did you get caught up enough? I don't want to--
[Dr. Ian Fields]
No, that's-- I feel like we're caught up enough to where we should be.
[Dr. Mark Hoffman]
Okay, good. I feel like I understand more now, so I appreciate that.
[Dr. Ian Fields]
Yes, good. I'm glad. We've at least established that urine not sterile.
[Dr. Mark Hoffman]
Not sterile.
[Dr. Ian Fields]
Right.
[Dr. Mark Hoffman]
I'm sure we'll turn off our notifications when people hear this one too.
[Dr. Ian Fields]
Oh, goodness.
The Microbiome & Urinary Tract Disorders
The interplay between the microbiome and urinary incontinence is complex, particularly in regards to stress incontinence and urgency urinary incontinence. The conventional understanding of stress incontinence is linked to functional aspects like pregnancy and childbirth, but new research indicates that the presence of specific bacteria in the bladder might predict the response to mid-urethral sling surgery. In contrast, the underlying causes of urge incontinence remain unclear, although disturbances in the urinary microbiome are tangibly linked. There is a multifaceted nature to urinary incontinence and the neurological pathways involved in urination are intricate, painting a broader picture of an area still ripe for research and exploration.
[Dr. Mark Hoffman]
What are ways that we think the microbiome is impacting disease processes and the urinary tracts of our patients?
[Dr. Ian Fields]
A lot of work has really been done specifically in urinary incontinence, so both the types of incontinence that I see as a urogynecologist, stress incontinence, which is leakage of urine that happens with activities like cough, laugh, sneeze, exercise, things like that, and urgency urinary incontinence, which is really a lot well less understood how that happens.
I think we can see how stress incontinence happens typically because of pregnancy, childbirth, you lose support of the urethra, therefore, activities that increase intra-abdominal pressure like cough, laugh, and sneeze could potentially lead to loss of urine involuntarily.
[Dr. Mark Hoffman]
That seems more of a functional thing. When you said you thought the microbiome had a role with stress incontinence, I was like, "I thought we understood that, because it was pelvic floor stuff and now you're saying there's like more to the story.
[Dr. Ian Fields]
There is, there is. When we think of stress incontinence specifically, a lot of the work has been done about response to surgery, and there was this large trial that was just presented and published I believe in the GREY Journal within the last year or so showing that the presence of different bacteria in the bladder at the time of surgery or before surgery could predict somebody's response to mid-urethral sling surgery. It was down to a couple different genera of bacteria that when present may potentially lead somebody to not respond as well to mid-urethral sling surgery.
[Dr. Mark Hoffman]
That seems crazy.
[Dr. Ian Fields]
We don't know why that is yet. It's just fascinating to me, especially on the flip side of things when we look at urge incontinence, we don't know why people get it. The hardest thing for me to say is people always want to know, "Well, why do I have urge incontinence? When I get the urge to go to the bathroom, why can't I make it to the toilet on time?"
The answer is we really don't know. The prevailing theory is that it's a way that the nerves in your body communicate with your bladder muscle. I always tell people the way we are designed to urinate is one of the most neurologically complex things that we do as humans, but we just don't think about it.
[Dr. Mark Hoffman]
A neurosurgeon that I worked with as a med student, that was his thesis, he just showed me a map of the micturition pathway and I was like, "That seems terribly complicated," but you got to know it's there, but you don't want to pee just yet and you got to be allowed to pee but you also got a control not peeing. It's just all of these things going back and forth between your brain and your bladder and your pelvic floor muscles all in concert. It's a miracle any of us are walking around dry, honestly.
[Dr. Ian Fields]
That's very true. Again, it's always a thorn in the side of the fellows that we train that learning that pathway and committing it to memory is really, really difficult. It's I think, one of the hardest things that we learn as fellows. There's a huge body of work showing that there are disturbances in the urinary microbiome, tangible disturbances that are linked to urge incontinence. I think that's one of the largest bodies of work that we have, is to show that alterations in that urinary microbiome may be more profound in somebody that has urge incontinence versus somebody that doesn't.
[Dr. Mark Hoffman]
It's fascinating. I'm just thinking about endometriosis. There's all this stuff we don't know. I just finished reading the Andromeda Strain. I don't know if you've ever read that before.
[Dr. Ian Fields]
Gosh, maybe when I was in middle school, I think.
[Dr. Mark Hoffman]
Well, I'm a little delayed. Well, no, we were at a used bookstore with my son and I was like, "Oh, I never-
[Dr. Ian Fields]
That's a great book.
[Dr. Mark Hoffman]
-read that." It's great, but how do you look for things you don't know even where to begin? I'm trying to think of other examples of that. Heartburn is one of those things we just assumed, but then turns out there's a bacteria involved that shouldn't be there. Is that more of an infection versus microbiome? Or is that a disturbance to the microbiome? What's the difference? Is that an example of--
[Dr. Ian Fields]
Yes, I think that's probably more an example of an infectious process that needs to be treated with antibiotics versus-- We don't fully understand. Just because these bacteria are there, I think this is the link that we're still waiting to uncover, which is why there's so much work to be done in this arena, because just because we know the bacteria are there people are like, "Well, so what? What does that mean now? How do we use this information?"
[Dr. Mark Hoffman]
Which of those bacteria are supposed to be there? Which of those bacteria may be causing the problem? Or which lack of what bacteria is allowing this problem to happen? It seems like there's a lot left to learn and a lot more to understand. As a basic scientist, how much of your job now is actually involving basic science research, any of it?
[Dr. Ian Fields]
None of it at this point in time. I did a lot more-- None yet, none yet. This was the focus of my fellowship thesis project, was the microbiome.
[Dr. Mark Hoffman]
Did you do basic science research in fellowship as well or just working with basic scientists?
[Dr. Ian Fields]
I was mostly working with basic scientists, although I did spend some time in the lab. There was a component of the project that I wanted to-- I wanted to do a basic science component in conjunction to the microbiome piece, but wasn't able to get that off the ground. Unfortunately, the collaborator who I worked with unexpectedly passed away during the time that I was in my fellowship, and so didn't get the chance to fully delve into that work like I had wanted to.
[Dr. Mark Hoffman]
Yes, and so when you go to a new place-- and that's unfortunate, but when you go to a new place, then you got to meet everybody again. Again, we talked about how people end up where they are, you just bump into somebody and go, "Oh hey?" Then it turns out your career goes sideways from there, a totally different direction. The challenge of being a basic-- Is it frustrating you at all, or is it something you want to keep doing? Because I am not a basic scientist. I math science in high school and I got to college and I was like, "I think I've done enough math."
Uterine & Intraperitoneal Microbiomes in Female Reproductive Health
New research may explain the potential influence of the microbiome on disorders such as fibroids, endometriosis, and chronic pelvic pain. The uterus and even the intraperitoneal cavity may have their own microbiomes, which may have been largely overlooked in past research. This previous lack of understanding and funding in these areas highlights the need for further exploration of these connections as the next frontier in research.
[Dr. Mark Hoffman]
Exactly. It's fascinating. You've certainly sparked my curiosity and all this stuff and now I'm like-- It's one of those things that once you know a little bit about it, once you get the idea that, "Oh wait, this is probably impacting a lot of things." Again, I deal with fibroids, endometriosis, chronic pelvic pain, a lot of these disease process is where we tell patients, "We don't really know where this starts. We don't really know how this happens."
We now know, at least a new lead to try to figure this out. Does the microbiome-- Because the Fallopian tubes things leak out. We talk about retrograde menstruation. There's bacteria in the vagina, possibly in the uterus. Is the uterus of microbiome? I imagine probably.
[Dr. Ian Fields]
Yes, there must be. I don't know of any off the top of my head, but I imagine that there must be, given the fact that you can have endometritis. It certainly is plausible that you can have something that potentially helps maintain homeostasis in the uterus..
[Dr. Mark Hoffman]
If we're talking about the urethra and how E. coli can travel, that's a day trip. I think if the vagina has its own microbiome and the cervix is only six centimeters long on average and people are menstruating about every month. Clearly there's some connection between the uterus and the vagina. I would imagine there would have to be. All of a sudden now I'm thinking, "Well, then there must be connection with intraperitoneal cavity." Again, we think of the abdominal cavities being sterile. Is it there a microbiome there?
[Dr. Ian Fields]
You bring up a good point. Again, I don't know of anything off the top of my head that anybody that has studied like peritoneal fluid, that would be just if you have a resident or a fellow who's chomping at the bit for something. Again, like the microbiome in--
[Dr. Mark Hoffman]
Sounds like one of your residents as opposed to one of mine, you're the expert.
[Dr. Ian Fields]
I think that's so fascinating. Again we think, especially with the work that you do with endometriosis and fibroids, like it's woefully underfunded, woefully understudied because it's underfunded and there's so much that we have--
[Dr. Mark Hoffman]
It's not understood.
[Dr. Ian Fields]
Correct, we don't know.
[Dr. Mark Hoffman]
It is frustrating to tell patients, "I just don't know." My wife is not in medicine but she is brilliant and reads, anytime anything comes up, she's pulling out journal articles and I'm like, "Where did you find this?" She likes to know an answer and she does not like it when doctors say, "I don't know how this happened."
[Dr. Ian Fields]
I think it's the hardest thing that we do as physicians sometimes is telling people we don't know.
[Dr. Mark Hoffman]
No, and it's hard to do and I don't think we're taught to do that. I think I'm pretty good at it. I'm happy to be honest. It's transparency. I can't promise--
[Dr. Ian Fields]
Same.
[Dr. Mark Hoffman]
-anything but honesty and transparency to my patients. We don't know. It sounds like if these old models of how endometriosis or of how we think endometriosis started, let us basically know where. Maybe this is the next frontier. You've got my wheels spinning.
[Dr. Ian Fields]
You have my wheels spinning too. Now I'm thinking, I'm like, "Oh, endometriosis and peritoneal," I'm thinking peritoneal fluid. That can't be that-- not something that communicate. Again, you have my wheels turning as well.
[Dr. Mark Hoffman]
Your wheels spinning are much more likely to produce valuable research than mine. If we've gotten someone wheel spinning, that's good news.
[Dr. Ian Fields]
You're too kind.
Podcast Contributors
Dr. Ian Fields
Dr. Ian Fields is a urogeyncologist and an assistant professor with OHSU School of Medicine in Portland, Oregon.
Dr. Mark Hoffman
Dr. Mark Hoffman is a minimally invasive gynecologic surgeon at the University of Kentucky.
Cite This Podcast
BackTable, LLC (Producer). (2023, February 23). Ep. 15 – The Microbiome [Audio podcast]. Retrieved from https://www.backtable.com
Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.
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