麻豆传媒

鈥淚 DON鈥橳 have to be afraid someone will smell what I smell,鈥� says Eden. 鈥淚 don鈥檛 have to be afraid to be in an intimate position. Bacterial vaginosis doesn鈥檛 manage me anymore.鈥�

Bacterial vaginosis (BV) isn鈥檛 a problem people normally talk about, despite it being the most common vaginal condition in women and girls aged 15 to 44. Caused by a change in the balance of vaginal bacteria, it produces grey, watery discharge that smells of fish. While antibiotics can treat the problem, for the vast majority of people they offer only .

Now, though, there is hope. It comes in the form of a vaginal microbiome transplant (VMT). Eden was one of the first five women in the world to receive such a transplant. The idea is simple: repopulate the unbalanced bacterial environment using fluid taken from someone with a healthy vaginal microbiome.

With early signs of success, the treatment is now being in the US. The hope is that such trials will lead to insights that will help the millions of people around the world who have recurrent BV.

It appears the vaginal microbiome is having a moment. Scientists have recently created the 鈥渧agina on a chip鈥� to better understand vaginal health and conditions, there is the ongoing search for 鈥渟uper-donors鈥� with the perfect vaginal environment, not to mention companies offering to test your vaginal microbiome from home. But how much do we really know about this intimate community of bacteria, viruses and fungi, and should we really be swapping it with someone else鈥檚?

Our microbiome 鈥� the microbes that live in our gut and elsewhere in and on our body 鈥� plays a crucial role in our health. Changes in our microbiome are linked with all manner of conditions, from heart disease and obesity to diarrhoea and depression.

Faecal microbiome transplants

In 1958, (FMTs) were trialled for the first time to treat bacterial infections. Researchers figured that if an imbalance of good and bad bacteria in the gut is behind a certain condition, then replacing it with the microbiome from someone who is healthier could solve the problem. Today, FMTs are approved in the UK and US for treating a subset of Clostridium difficile infections that are unresponsive to antibiotics and, in some cases, potentially deadly. Since 2012, the non-profit organisation , treating more than 65,000 people with C. difficile. A recent trial also successfully used FMTs to treat people with irritable bowel syndrome.

It wasn鈥檛 until the past decade that researchers considered doing something similar with the vaginal microbiome, which is linked to its own host of conditions, including BV, pelvic inflammatory disease, recurrent yeast infections and .

BV was the first condition to be studied with VMTs in mind. It affects around and can increase the risk of sexually transmitted infections, reduce fertility and cause adverse pregnancy outcomes, including premature birth. Up to . The incidence in trans men is unknown.

Correcting an out-of-sorts microbiome by transplanting a cocktail of bacteria from a 鈥渉ealthy鈥� vagina may sound like a simple solution. But there were immediate hurdles, not least that it quickly became apparent no one really knew what a healthy vaginal microbiome looked like.

At first glance, the vaginal microbiome appears relatively simple, as microbiomes go. In general, it has less bacterial diversity than, say, the gut. It is mostly a delicate balance of different species of the Lactobacillus genus. However, it becomes considerably more complex when you consider that there is no one way for a vaginal environment to be, with this ecosystem changing throughout a person鈥檚 life, during pregnancy, menopause and even on a monthly or daily basis.

The causes of bacterial vaginosis

Inevitably, this has made it hard to work out how the vaginal microbiome changes in conditions like BV. For instance, studies suggest that . Another bacteria, Gardnerella vaginalis, is nearly universally present in people with BV, but some people with G. vaginalis don鈥檛 have symptoms, says microbiologist . 鈥淎s a result, the definition of BV is difficult,鈥� says Buck. 鈥淚t鈥檚 a bit wishy washy.鈥�

Nevertheless, with little else to offer people with recurrent BV like Eden, at the Hadassah Medical Center in Jerusalem forged ahead with a .

Her team began by giving five women with recurrent BV (including Eden) antibiotics to suppress their vaginal microbiome. A week later, they collected vaginal fluid from three donors who hadn鈥檛 experienced BV in the past five years, using a spatula-like device designed for cervical screening. Within the hour, each sample was diluted with saline solution. Each recipient received a portion of fluid from a single donor, just behind the cervix.

At regular follow-ups, the recipients鈥� symptoms were checked and their vaginal fluid analysed. They were offered up to three repeat procedures if symptoms of BV returned between follow-ups. Four out of five of the women, including Eden, had no symptoms up to 21 months after their final transplant, when the study period ended. The fifth had a significant reduction in symptoms.

Broadly speaking, then, the trial was a success. But many questions remained. One of the participants only went into remission after she changed donors, for instance. What was in the second donor鈥檚 microbiome that helped that wasn鈥檛 in the first?

One answer may be that a healthy vaginal microbiome isn鈥檛 just about the presence of one particular kind of bacteria, like certain species of Lactobacillus, but several working in collaboration. We know, for instance, that wiping out the unhealthy microbiota associated with BV using antibiotics doesn鈥檛 encourage the growth of good bacteria, says Lev-Sagie. 鈥淚t takes away the bad bacteria, but then they come back.鈥�

Likewise, , with any benefits short-lived. Lev-Sagie estimates that about six to 10 different species of bacteria were transferred in the donors鈥� fluid in her pilot trial. How many of them contributed to the final result, and which made the biggest contribution, is unknown.

In fact, perhaps it is wrong to give bacteria the credit at all. Vaginal fluid also contains things like skin cells, mucus, sugars, viruses, fungi, electrolytes and proteins. There are many unknowns regarding how different aspects of the vaginal environment communicate with each other and whether miscommunications can lead to medical conditions, says immunologist at the Weizmann Institute of Science in Rehovot, Israel.

Bacterial vaginosis treatment

Lev-Sagie and her colleagues are now . A similar is also under way at Massachusetts General Hospital. Trans men who aren鈥檛 on hormone therapy and who haven鈥檛 had gender-confirming surgery are also eligible to join. In both trials, the groups will be split, with one half receiving a transplant from donors with 鈥渉ealthy鈥� levels of Lactobacillus and the other half receiving a placebo.

Identifying exactly what works and why won鈥檛 be easy. Not only does the vaginal microbiome change during pregnancy, the menstrual cycle and menopause, sex, vaginal douching (washing the inside of the vagina), applying perfumed products to the vulva and using intrauterine contraceptive devices can also throw things out of whack. 鈥淲e see daily fluctuations,鈥� says Lev-Sagie. We can somewhat control for these factors in trials, for example by not taking donations during pregnancy or asking recipients to abstain from sex before the study. But these frequent changes are part of the reason why the vaginal microbiome has remained unexplored for so long.

Differences in the vaginal microbiome have also been . These differences could come down to things such as genetics, access to healthcare or variations in diet. 鈥淭he jury is still out,鈥� says Elinav.

Vagina on a chip

Nevertheless, inroads into understanding the vaginal microbiome are being made. team at Harvard University has recently developed a . This silicone chip contains vaginal tissue that is washed with a hormone-filled fluid. It is responsive to fluctuating hormone levels and bacteria 鈥� mimicking the real vaginal environment. By changing the tissue sample and the fluid contents, the chip could make it easier to understand how different people鈥檚 vaginal microbiomes change in different environments and to test new treatments.

Then there are hopes that trials may identify 鈥渟uper-donors鈥�, whose vaginal fluid is top class, who could right the microbial wrongs of a wide range of people with BV. However, with VMT trials few and far between, identifying a super-donor 鈥� whose fluid would have to prove its worth by treating a large number of recipients 鈥� will take time. Not everyone is convinced it is even possible. Getting healthy bacteria to colonise a vagina isn鈥檛 a slam dunk, says Bunk. You need precise conditions and what these are is still an open question.

Of course, as with any transplant, there are questions over the safety 鈥� and ethics 鈥� of VMTs (see 鈥淭he ethics of swapping bodily fluids鈥�, left). Donors are screened to make sure they have no sexually transmitted infections or unusual bacteria present. They are given a gynaecological examination and complete a medical questionnaire. Lev-Sagie is confident that the vaginal fluid they transfer is safe, and no side effects were experienced by any of the five participants in her pilot trial. But some researchers worry that screening isn鈥檛 enough. In rare cases, , says Buck. 鈥淓ven though we have pretty good ways to determine what is in a sample, we really can鈥檛 guarantee what鈥檚 in it.鈥�

A solution could be to create a lab-made cocktail containing only the 鈥渞ight鈥� bacteria. Lev-Sagie hopes her larger study will identify the key bacteria that could be used in an at-home probiotic treatment. But such a product may be some way off. 鈥淭he vaginal microbiome is complicated. How long will it take to produce, in a clean way, the components that are crucial to cure different vaginal conditions?鈥� says at Rutgers University in New Jersey.

Test your vaginal microbiome

Given the uncertainties around what a healthy vaginal microbiome looks like, it may come as a surprise to hear that companies such as in London are offering to give you insights into your own, using a simple at-home test kit. A swab from the vagina is sent to their labs and your microbial DNA is analysed. The firm sends you a report with what bacteria are present, what they are known to do and what effect they might have on your health.

鈥淭hey will tell you your microbial profile, but so what? What are you going to do with it?鈥� says Dominguez-Bello. Even if you are told you have a profile that resembles those with BV, if you are asymptomatic, the information may be redundant, she says. Juno Bio didn鈥檛 reply to 麻豆传媒鈥榮 requests for comment.

What is clear is that there are still a lot of hurdles before we really get to grips with the vaginal microbiome or how to tweak it to our advantage, but also that the new interest has great potential to help a vast number of people. 鈥淎djusting the microbiome is a huge question,鈥� says Elinav. 鈥淲e鈥檙e just starting to scrape the surface of how we could alter these very complex microbial communities.鈥�

For Eden, the mere attempt to do so was 鈥渓ife changing鈥�. Now the vaginal microbiome is finally getting the attention it deserves, the next few years may see thousands more people experience the same reaction.