Bacterial vaginosis associated bacteria may increase a women’s risk for miscarriage

Bacterial infections or even slight imbalances can be damaging at many difference locations in the human body. One that should be taken seriously in bacterial vaginosis, which is an infection in females where a healthy bacterial balance is taken over by bacteria such as Gardnerella vaginalis, Ureaplasma urealyticum, and Mycoplasma hominis to name a few. Meanwhile, the presence of Lactobacillus crispatus and Lactobacilus iners would be characteristic of a normal vaginal microbiome. In a study out of Philidelphia, Pa that was recently published by Maternal and Child Health Journal, researchers inspected a possible connection between bacterial vaginosis and pregnancy miscarriages.

          A total of 418 pregnant women were included in the study. 65% of the women were African American, 27% were Hispanic, and 4% were Caucasian. Women were eligible if they were seeking treatment prior to 14 days of gestation, if they were not pregnant with multiples, and if there were no issues in terms of ectopic or molar pregnancy. Swabs were collected from the women and analyzed. During this study, 74 women experienced a miscarriage, while 344 delivered at term.

          It was found that the group of women who had miscarriages were older than those who did not. Women with high concentrations of Bacterial Vaginosis-Associated Bacterium 3 (BVAB3) before 2 weeks gestation had a 20% increased chance of miscarriage. On the other hand, for each one unit increase in Leptotrichia/Sneathia species concentration, risk of miscarriage decreased by 20%, and for that of Megasphaera phylotype 1-like species risk decreased by 19%. The implications of this type of research could be very beneficial to women everywhere. More knowledge like this could hopefully one day lead doctors towards even better care for pregnant women. Ideally, with more research into this area, the prevalence of miscarriages could be lowered. 

Study suggests penile microbiome can transmit bacterial vaginosis by sexual intercourse

Bacterial vaginosis (BV) is a microbiome-based disease characterized by a lack of Lactobacillus in the vagina.  We have covered this disease with multiple blog posts and encourage any interested readers to search for these blogs to learn more.  One outstanding question regarding BV is how sexual intercourse affects the disease.  One prevailing thought is that the penis can actually be colonized by BV-associated bacteria, and that through sexual intercourse it can be spread between partners.  A new paper published last week in mBio suggests this is true.

The researchers measured the penile microbiomes of 165 uncircumcised, black men from Uganda, as well as diagnosing BV status in their female partners.  The BV status was measured by Nugent score, which is a bacterial staining technique that basically measures the amount of anaerobic bacteria in the vagina (non-Lactobacilli).  The stain produces a score between 1-7 with 1 being healthiest and 7 being least healthy (mostly anaerobic bacteria).  After measuring the penile microbiomes, the scientists were able to be categorize them into 7 different community state types (CST1-7).  These community state types varied from 1 to 7 in terms of both overall abundance and composition, with CST1 having the lowest density of bacteria and the lowest diversity while CST7 had the highest density and the highest diversity of bacteria.

The scientists compared the female partner’s BV status with the men’s community state type, and noted that having a CST1-7 on the penile microbiome corresponded with a higher likelihood of the female partner being diagnosed with BV.  Two genera of bacteria, Corynebacterium and Staphylococcus, on the penile microbiome were associated with healthy vaginal flora, whereas Dialister, Mobiluncus, Prevotella, and Porphyromonas were associated with BV.  Interestingly penises that included Lactobacillus and Gardnerella, genera associated with healthy vaginas and BV vaginas, respectively, were not statistically associated with BV status.  Overall, men with CST4-7 were significantly more likely to have a sexual partner with BV, and had more BV associated bacteria colonizing their penises.  In addition, men with more than one sexual partner were more likely to have CST4-7, and again, their partners more likely to have BV.

It appears that men’s penises, especially uncircumcised ones, can be vectors for bacterial transmission.  This simple fact should make us reconsider BV as an STD, and actually fits in well with another that has shown promiscuity is a risk for BV.  It is likely that circumcision and condom would decrease BV transmission rate, as they do other STDs, but until a paper comes out that studies this connection no one can say for sure.

New research helps determine what is healthy and unhealthy in the vaginal microbiome

Editor’s note: This blog about the vaginal microbiome is a good primer for this coming Monday’s Microbiome Podcast with Jacques Ravel, where we will discuss the vaginal microbiome and women’s health at length.  There will also be a special announcement during this podcast, so anyone interested should be sure to download it Monday, June 1.

The typical ‘healthy’ vaginal microbiome is dominated by a Lactobacillus.  However many women, especially those of African descent, are not dominated by this genus, and instead have a high diversity of bacteria in their vaginal tract.  This low lactobacilli, high diversity phenotype has been associated with many disease states, such as bacterial vaginosis (BV), preterm birth, and higher rates of sexually transmitted disease (STD) transmission.  (We have written about some of these diseases before, and encourage any interested reader to click the ‘vaginal microbiome’ below this story to learn more.)  Vaginal microbiome research is still in its early days though, and it is not clear why vaginal microbiome not dominated by Lactobacillus should lead to these diseases, and if this phenotype, if asymptomatic, should even be considered unhealthy.  New research though, out of Harvard University, shows that this phenotype does lead to inflammation, and that these inflammatory response can affect reproductive health and STD transmission.  They published their study in the journal Immunity last week.

The scientists studied the vaginal microbiomes of a cohort of 146 HIV negative, asymptomatic, black, South African women.  They discovered that 63% of them were not dominated by Lactobacillus, an extremely high percentage, especially compared to their counterparts in developed countries (38% of black women and 10% of white women).  Nearly half of those women were dominated by Gardneralla vaginalis, which is most commonly associated with BV, and a large percentage of the other half were diagnosed with BV after investigation.  This is especially interesting because, as stated before, all of the women in the cohort claimed to be asymptomatic, but as we are learning, many women are unaware that there is anything wrong.  Overall, the women were able to be grouped into 4 specific phenotypes, those dominated by Lactobacillus iners, those dominated by other Lactobacillus crispatus, those dominated by Gardnerella vaginalis, and those with a high diversity including Gardnerella vaginalis, Fusobacterium gonidiaformans, Prevotella bivia, and Atopobium vaginae (note the lack of Lacotbacillus in this high diversity group). 

The scientists discovered that there were no associations between each vaginal microbiome group and the rate of STDs, contraceptive use, or sexual behavior.  This is important in showing that, at least on first pass, these bacterial communities were not the result of these exogenous factors (nor did they cause them, for that matter).  They also discovered that there was only a loose association between inflammatory cells in the vaginas of these women, and whether or not they had an STD.  The loose association was only observed in women with Chlamydia, and the women with the highest levels of inflammation had no apparent STDs.

The fact that STDs were not strongly associated with inflammation led the researchers to hypothesize that the vaginal microbiome community, rather than STDs, were responsible for vaginal inflammation.  Indeed, when they compared the amount of inflammatory cells in each vagina with the different microbiome groups described earlier, they found a strong association between inflammation and the highly diverse microbiome group.   Moreover, when they tracked individual women over time, those women whose vaginal microbiomes shifted to the high diversity group also increased inflammatory responses.  The researchers then took this work a step further, and identified specific bacteria that were associated with the inflammatory response:  Prevotella amnii, Mobiluncus mulieris, Sneathia amnii, and Sneathia sanguinegens.

Finally, the researchers measured genes for specific receptors in the vagina that are known to trigger an immune response.  They discovered that those women with the high diversity vaginal microbiomes upregulated genes for these receptors, which are known to be activated by bacteria.  Making matters worse, specific immune cells that are triggered by these receptors, which are thought to be critically important to HIV transmission, were found in higher abundances in women in the high diversity vaginal microbiome group.

This paper did a really great job showing that a vaginal microbiome that lacks Lactobacillus is indeed an unhealthy state, because it creates a highly inflammatory vaginal microbiome which likely causes or contributes to many other ailments, beyond just the higher rates of HIV transmission that was demonstrated.  Unfortunately, at the moment, there are no easy ways for women to check which vaginal microbiome they have, but that should be changing soon, and we recommend that all of our readers tune into the Microbiome Podcast this coming Monday to hear a big announcement in this area. 

How does a man’s seminal microbiome alter a woman’s vaginal microbiome?

There is very little research on the microbiome of semen.  We know that it is not sterile, and some scientists think that some of the bacteria found in semen may be involved in male fertility issues.  However, there is still a lot of research to be done in this area.  Even less is known about how the seminal microbiome influences the vaginal microbiome after sex.  Some research has suggested that specific sexual partners can cause bacterial vaginosis (BV), however the mechanisms for this are unclear.  It is suggested that perhaps the penile and seminal microbiome being transferred to the vagina during sex could cause this, although research has not confirmed these hypotheses.  Researchers from Estonia tried to answer these questions, and studied just how the vaginal and seminal microbiomes change before and after sex.  They published the results of their findings last week in Research in Microbiology. 

The scientists measured the seminal and vaginal microbiomes before and after sex for 23 couples who had sought help for infertility but were otherwise healthy.  They learned that the seminal microbiome, while containing much fewer bacteria, was actually more diverse than the vaginal microbiome.  Still though, each shared many of the same bacteria.  These included Lactobacillus, Veillonella, Streptococcus, Porphyromonas and Atopobium.  Interestingly, Gardnerella vaginalis, a bacterium highly implicated with BV, was found more frequently in women who had sex with men whose semen contained leukocytes, itself a phenotype associated with infertility.  While most of the women’s microbiomes did not shift after sexual intercourse, four of them did.  In these women a decrease in Lactobacillus occurred, and a decrease in Lactobacillus has also been highly implicated in BV.

While this study was preliminary, it marks some of the first research on the dynamics of the seminal and vaginal microbiome during sex.  The scientists suggest that the microbiome may be very important to fertility issues, and at the AMI we would not be surprised to learn that it is involved in at least some causes of infertility.  In the near future we will be devoting an entire podcast to the vaginal microbiome, and interviewing Jacques Ravel, a world leader in this field.  If you have any relavent questions and would like us to ask them on the podcast please call 518-945-8583 and leave your question on the voicemail.