Antibiotics, Probiotics and the Vaginal Microbiome

The vaginal microbiome has a unique relationship with antibiotics, probiotics and hormones. I recently had the opportunity to discuss this relationship with Dr. Jennifer Balkus, PhD, MPH, infectious disease epidemiologist at the University of Washington. As a researcher studying the interface between the vaginal microbiome and HIV/STI prevention, she is the Associate Director of the Microbicide Trials Network Statistical and Data Management Center, and is also a member of the Kenya Research and Training Center at UW, where she conducts research related to assessing the impact of the vaginal microbiome on adverse reproductive health outcomes in women. 

1. Your 2011 and 2012 research explored vaginal microbiome disturbances and maintenance regimens. Research is mixed regarding the efficacy of oral probiotics for promoting a healthy vaginal microbiome, yet probiotic brands such as Culturelle® and RepHresh™ continue to be marketed towards women. Is there potential for oral probiotics to aid in establishing and maintaining a healthy vaginal microbiome? 

The work that I do really focuses on the paradigm of what we consider “optimal,” and I define optimal as the vaginal microbiota that has been associated with the lowest risk of adverse outcomes, such as sexually transmitted infections and adverse pregnancy outcomes. So this environment, and the environment we are typically aiming for, is typically dominated by lactobacillus species and not much else. One shift that can happen is the loss and replacement of those lactobacilli with anaerobic and Gram-negative bacteria that are associated with a clinical condition called bacterial vaginosis (BV). Many terms are often thrown around regarding the vaginal microbiome and the microbiota, so I want to be precise because it impacts your question about the role that probiotics play in this environment.

When an individual has BV, they may have symptoms such as white or gray watery discharge, but some individuals may be colonized with BV-associated bacteria and remain asymptomatic. With BV, the treatment we have used for the past 60 years or so has been antibiotics, with the two most common being metronidazole and clindamycin. Because the most prominent bacteria remain susceptible to these antibiotics, you first see a rapid decrease with this medication and then there’s a pause where you aim to see the reestablishment of lactobacilli. For some individuals you don’t see that. You see the decrease but then you may see slow, or even rapid, recolonization with the BV-associated bacteria. This is where it's really challenging because with those individuals, even if they’re not symptomatic, they’re still at higher risk of STIs and other adverse outcomes that we’d be concerned about.

To your point about antibiotic use and what we’re investigating, questions arise such as: Is one round of antibiotics for certain individuals enough? Do they need to be on a suppressive regimen where they’re taking an antibiotic continuously? Do they need an intravaginal regimen with a more local, less systemic impact? Each of these approaches definitely reduces BV, both the clinical condition and the associated bacteria, but there is often this rebound backwards so it’s not a great long term strategy for dealing with recurrence, and it’s also not great to have people remain on antibiotics indefinitely.

While much probiotic research includes the lactobacillus species we want to see in the vagina, the most promising research has not come from oral probiotics. For the oral probiotics currently over the counter, these are not evidence-based approaches as the research is not strong

enough. One of the challenges when thinking about oral probiotics is that the bacteria need to be in the vagina. And if you’re taking oral probiotics they’re going to end up in the gut. There is some bacterial transfer from the rectum to the vagina that can occur naturally just due to proximity and hygiene and such, but if you’re really trying to get a robust amount of lactobacillus bacteria to the place where there’s an issue, I don’t believe the gut-rectum pathway is going to give you the optimal dosing you’d want, and would look instead to vaginal suppositories to establish colonization.

The one approach that has been evaluated as a live bio-therapeutic after going through the FDA bio-therapeutics process is a product called Lactin-V, a lactobacillus suppository. This was evaluated amongst individuals with BV where they first received antibiotics to eradicate the BV-associated bacteria, and then were given these vaginal lactobacilli suppositories to try and promote lactobacilli recolonization. It’s a superhero approach to the vagina, if you will, this idea of wiping out the “bad” bacteria and swooping in with the lactobacilli because their presence will help maintain a more optimal pH and delay infection recurrence. This Lactin-V study was published in the New England Journal last year, and they did find a reduction, or a delay, in recurrence. It was fairly modest, but it was great proof of concept.

2. Research shows that estrogen may have a protective effect against bacterial vaginosis and UTIs. Other research highlights estrogen as a risk factor for developing vulvovaginal candidiasis. In moving from research to clinical practice, how do we navigate the complex relationship that exists between hormones and vaginal health, when certain hormonal treatments may either improve or worsen the vaginal microbiome depending on the microbe in question? 

One of the biggest challenges in moving from research to clinical practice is that much of what we’re looking at is happening at the population level, but when a clinician is sitting with someone in their office and thinking about what is best for the patient in front of them, that’s an individual level. So in navigating this, I think it is important to continue to understand what the preponderance of evidence says. For example, among individuals who take estrogen-containing hormonal contraceptive pills, we do tend to see a lower incidence of BV, so this medication may be protective against this infection, but that’s not to say that someone taking this medication will never have BV.

This is where it’s good to step back and examine the overall pattern of vaginal infections a patient has experienced. If someone has experienced recurrent BV in their life and they’ve taken antibiotics that only delay recurrence, then it’s possible that, if they were interested in hormonal contraception, estrogen-containing hormonal contraception could be a complementary strategy based on what the observational data has shown. Whereas on the other side, for example, the copper IUD is associated with an increased risk of BV, so if a person has a history of BV then a copper IUD may not be their optimal strategy because it could further exacerbate these issues. Additionally, this is overlapping with variables such as sexual activity and partnerships which makes these relationships really difficult to disentangle. For folks that are struggling with recurrent infections such as UTIs, vulvovaginal candidiasis, or BV, I think both provider and patient need to understand the potential pros and cons of each option, and choose one that is either protective, or at least neutral, in terms of being a risk factor for infection recurrence.

3. With the COVID-19 pandemic highlighting how important science communication is, do you have any tips on how public health professionals can improve their science communication skills? 

To be honest, I am very much still learning. The key things to think about beforehand, especially when you’re communicating with journalists, is to understand what their questions are, who their audience is, and what your message is. The audience is often individuals with no scientific background and many different perspectives, so you really want to be sure you’re clear on what your message is. When you’re trying to distill information, whether it’s on Twitter or with a reporter, having those clear, bulleted take home messages is important. Nowadays, with so many people on the news talking about COVID-19, if I randomly turn on the radio and hear this person, what is their statement? What is their take-home message? Sometimes metaphors can be helpful, but it all really depends on the situation. It’s key to focus on what the messages are, why they are important to public health, and to remain honest about where we’ve succeeded and where we’ve failed. I think the biggest concern is when we are not honest about our failures, because it contributes to mistrust in the system and this can be really hard, especially facing the crises that we’re facing now. But yes, accountability and honesty are incredibly important in science, policy and communication.