The Next Frontier of Microbiome Transplants May Be the Vagina

Don’t try this at home

This story was updated on Oct. 7, 2019 to reflect new study data.

There is new research that proposes that the best way to treat a bacterial infection in one woman’s vagina might be to transplant bacteria from another woman’s vagina.

Our bodies are home to a diverse ecosystem of bacteria. Different body parts host different bacterial communities and require a specific balance of microbes to stay healthy. In the vagina, one strain reigns supreme: Lactobacillus. One theory as to why Lactobacilli are beneficial is that they produce lactic acid, keeping the vaginal pH relatively acidic and killing off most of the other types of bacteria. If Lactobacillus is usurped as the dominant strain, a type of inflammation called bacterial vaginosis (BV) sets in, and there’s an overgrowth of other kinds of bacteria.

“High diversity is very healthy in the gut. In the vagina, it’s the total opposite,” says Jacques Ravel, a professor of microbiology and immunology at the University of Maryland. “That’s what defines BV — it’s what they call a polymicrobial disease. That means you have many different microbes that you really don’t want to be there.”

BV is the most common vaginal infection among women, with an estimated prevalence of about 30% among women ages 14–49 in the U.S. It can cause discharge, a fishy odor, itching, or burning in the vagina, although not all women with BV are symptomatic. The condition can also be associated with an increased risk of urinary tract infections. More pressing, in some cases BV can lead to preterm birth in pregnant women and a greater risk for sexually transmitted infections, including HIV and cancer-causing HPV.

The standard treatment for BV is antibiotics that are supposed to eliminate the non- Lactobacillus microbes and allow the good bacteria to regrow. However, in most women the relief is temporary and the infection recurs within two to four weeks. Another approach is to give women a probiotic containing Lactobacillus either vaginally or orally, but so far the results have been mixed. So scientists are searching for alternative treatment options.

Two groups of researchers in the U.S. — at Johns Hopkins University and Massachusetts General Hospital — and one group in Israel are taking a creative approach: vaginal microbiome transplantation. The researchers believe that transplanting an entire microbial colony, rather than just one species (like in the probiotic approach), could be the secret to helping the good bacteria regain control from the bad bacteria.

“Probiotic studies have been trying to do this for years and years and have not been successful. But very few of those studies actually look to see if the probiotic they’re using colonizes the vagina, and stays in the vagina after people stop taking it,” says Caroline Mitchell, director of the Vulvovaginal Disorder Program at Massachusetts General and head of their clinical trial to test the theory. “Our thought with the whole vaginal fluid transplant is that some mysterious factor that’s supporting the Lactobacillus may be the thing that’s good and beneficial in and of itself.”

“There has not been a dramatically new or different treatment for bacterial vaginosis in decades, which is a sad commentary on the state of funding for research in women’s health and specifically vaginal health.”

Although it sounds extreme, there is a precedence for microbiome transfers, most notably in the gut. Fecal microbiota transplants (read: poop transfers) are used to treat severe infections caused by the bacteria Clostridium difficile, or C. diff. Fecal transplants are up to 90% effective at treating C. diff and are becoming one of the first-line treatments for the infection.

The Israeli group published the first successful clinical trial of the procedure, showing that four out of five women benefitted from the transplant, with their BV going into complete remission for up to 21 months. Those four women also had a repopulation of Lactobacillus microbes. In two of the women, the treatment was effective immediately, while the others required multiple vaginal microbiota transplants to alleviate their symptoms, sometimes from the same donor and sometimes from a different one. The scientists say a larger clinical trial is needed to understand why some of the transplants were successful and some were not.

A paper by the Johns Hopkins scientists — who have not started testing yet — outlines how to identify women who might be optimal vaginal microbiome donors. The researchers first screen women for any viral and bacterial infections. They then make sure Lactobacillus is the predominant bacteria strain in the potential donors’ vaginal microbiome. Finally, because BV may be transmitted sexually by introducing new bacteria to the vagina, the researchers seek donors who are sexually active, although not while they’re enrolled in the trial. This way, the researchers know that the women had the opportunity to get BV but never did, suggesting they may have a resistance to it. Out of 20 women screened in the study, only seven met the stringent criteria.

To obtain the fluid, the researchers use menstrual fluid cups that are inserted into the vagina and collect mucus off of the vaginal and cervical walls. The goal is to get half a milliliter of secretions, combine it with another fluid to thin it out slightly, and then use a syringe or eye dropper to insert it into the recipient’s vagina.

For Laura Ensign, an associate professor of ophthalmology at Johns Hopkins (with secondary appointments in the departments of Gynecology and Obstetrics and Infectious Diseases) and senior author of the paper, success would be finding evidence of the donor bacteria in the recipient. “For the first study, [we’re] planning to follow the recipients for several months, not only looking at can you find the donor species there, but also what does the community look like, how do the dynamics change over time, and does the bacterial vaginosis recur or not?” she says.

Regardless of whether the treatment works, the researchers say that just attempting it is a step forward for women’s health. “There has not been a dramatically new or different treatment or intervention for bacterial vaginosis in decades, which is a sad commentary on the state of funding for research in women’s health and specifically vaginal health,” says Massachusetts General’s Mitchell. “Even if this particular design does not work, I think [we] are doing something that will advance our understanding of this field in a way that is totally necessary.”

Health and science writer • PhD in 🧠 • Words in Scientific American, STAT, The Atlantic, The Guardian • Award-winning Covid-19 coverage for Elemental

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