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. 

Identifying probiotics using healthy individuals for preventing oral disease

The oral microbiome consists of many hundreds of species of bacteria, some harmful and some beneficial. The importance of a healthy microbiome should be stressed not only because having clean, white teeth looks good but because diseases like periodontitis increase risk of other issues such as respiratory infections and inflammatory diseases. Having unhealthy teeth can cause more systematic problems than you would think. Probiotics, different from antibiotics, are one way that microbiome science is combating the colonization of harmful bacteria in the body. Many researchers have investigated using probiotics to maintain a normal healthy oral microbiome, and in a new study published last week, scientists researched probiotics that may reduce the smell of “bad breath” that is caused by volatile sulfur compounds, and prevent cavities and periodontitis.

The study, performed by researchers at the Yakult Central Institute for Microbiological Research in Tokyo, Japan (a division of Yakult, the makers of yogurts and probiotics),  was aimed toward finding new potential probiotic candidates. Thirty-two volunteers were recruited and selected based on factors such as non-smoking habits, no large cavities or bleeding on probing, and no bad breath. Oral bacteria samples were taken from multiple specific locations in the mouth of the volunteers. The bacteria were cultured in a lab and tested for the characteristics that follow: lack of production of volatile sulfur compounds (causes bad breath) and water insoluble glucan (causes cavities), antibacterial activity against bacteria that cause periodontitis, ability to healthily adhere to teeth and cells in the mouth, and caused no infections in an artificial mouth system or in a rat model.

After culturing in a lab and testing the criteria on 896 oral samples from the 32 participants, the study found that Lactobacillus crispatus YIT 12319, L. fermentum  YIT 12320, L. gasseri YIT 12321, and Streptococcus mitis YIT 12322 are good candidates for probiotics.  The next step is to now test for these probiotics’ effects in the mouths of many people, and likely develop a product.  Interestingly, L. crispatus and L. gasseri are two of the major bacterial strains found in a healthy vaginal microbiome, and perhaps this suggests a route of access for these bacteria to access the vagina. In any case, the promise of new ways to help maintain a healthy oral microbiome is exciting, and it is encouraging to read papers from major companies that have the ability to actually manufacture products in this space.

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.