New contraceptive vaginal ring does not increase risk of vaginal infections

The Nuvaring, a type of vaginal ring.

A newly developed contraceptive device that consists of a vaginal ring that is meant to be used for an entire year is currently under development.  As part of this device’s safety trials the scientists who developed the device monitored how it would impact the vaginal microbiome.  The vaginal microbiome is critical to vaginal health, and certain changes to the vaginal flora are associated with bacterial vaginosis (BV), yeast infections, and other vaginal diseases.  Implanting devices will certainly affect the vaginal microbiome, but fortunately, the scientists determined that the device did not increase the likelihood of getting a vaginal microbiome-mediated disease.  They published their results last week in PLoS ONE.

The vaginal microbiomes of 120 women using the device were measured over the course of a year.  There were no significant increase in the rates of BV over the course of the year.  In addition, the levels of Lactobacilli, which are associated with a healthy vagina, and Gardnerella vaginalis, which has been associated with BV, remained relatively unchanged over the course of treatment.  In addition, measurements on the actual surface of the vaginal ring matched the overall vagina quite well in terms of microbial colonization. In both cases, Lactobacilli dominated.

Any fluid or device inserted into the vagina should be considered for its effect on the vaginal microbiome, for example, douching is associated with BV.  Fortunately, this safety study showed that the vaginal ring did not increase rates of disease, so women out there using a vaginal ring for contraception need not be too concerned that their ring is negatively impacting their vaginal health.

Probiotic shows effectiveness against skin allergy in mice

We’ve talked about atopic dermatitis on the blog before, because more and more evidence is linking this autoimmune disease with the microbiome.  In fact, a few weeks ago we wrote about a strong connection between Staphylococcus aureus and atopic dermatitis, which suggests this bug is the culprit behind the disease.  If atopic dermatitis does have a microbiome cause, then it makes sense that shifting the microbiome could help alleviate the disease.  This past week researchers investigated whether probiotics, specifically Lactobacillus casei, could help treat this disease in mice.  They published their results in the Journal of Applied Microbiology.

Scientists induced groups of mice to have atopic dermatitis by shaving their skin and challenging them with a molecule called trimellitic anhydride (TMA) on various days over the course of two weeks.  During that time, the scientists orally administered the probiotic to some of the groups of mice.  Over the course of the study the scientists measured various things like the changes in the microbiome and the amount of various immune-activated molecules, as well as dermatitis indicators, such as skin lesions and the amount of itching.  They discovered that the mice that took the probiotic had less severe symptoms than those that did not.  What’s more, is that this reduction of symptoms occurred in a probiotic dose-dependent manner, i.e. the more probiotic administered, the better the symptoms.  These symptoms included a reduction in the inflammatory response, as well as a desensitization of the TMA, as evidenced by less itching.  As for the microbiome, treatment with TMA decreased abundance of Bifidobacterium and Lactobacilli, and an increased abundance of Clostridia.  Probiotics on the other hand, increased the abundance of Lactobacilli and Bacteroides and decreased the abundance of Clostridia. 

This study is not the first to show in a health improvement through the administration of Lactobacillus, which we have written about before.  It seems this bug is almost always associated with health, except in the case of respiratory diseases.  Overall, it seems that you can’t get enough Lactobacilli, so the next time you are considering having a second serving of yogurt for breakfast, go right ahead.

Episode 8 of The Microbiome Podcast: The vaginal microbiome and the announcement of a new citizen science project with Dr. Jacques Ravel

This week's episode of The Microbiome Podcast featured Dr. Jacques Ravel from the University of Maryland School of Medicine talking about the vaginal microbiome. We all also talked about a new project that Dr. Ravel helped start called Your Private Biome, an open source citizen science project designed to help researchers get a better understanding of how all the bacteria in women’s vaginas – the vaginal microbiome - affects their health. The new project launched today, June 1st, and the AMI is sponsoring free sampling for a number of women and possibly her partner or family members. If you'd like to learn more, click here. Remember to call in to ask any questions about the microbiome that you would like answered on future podcasts. The number is 518-945-8583. 

Listen to the podcast here on our website, here on iTunes, and here on Stitcher. 

For more detailed show notes, read below:

• (1:20) The White House Office of Science and Technology Policy issued a Request for Information (RFI) to solicit ideas from various stakeholders on the future needs of microbiome research. Read the RFI.
• (2:55) A recent paper out of Curtis Huttenhower’s laboratory describing how microbiome samples could be traced back to their hosts and if this could be used to track individuals related to forensics and other applications. Read the paper. Read our blog post on the paper. 
• (5:22) We begin our conversation with Dr. Jacques Ravel. Read more about Dr. Ravel’s research. 
• (5:47) Dr. Jacques Ravel gives an introduction to the vaginal microbiome. Read more about his research laboratory at the University of Maryland School of Medicine.
• (8:23) Dr. Ravel mentions a paper by Dr. Larry Forney about the vaginal microbiome of adolescent girls. Read the paper.  
• (20:10) Other health issues related the microbiome such as bacterial vaginosis and STDs.
• (30:30) A new citizen science project called Your Private Biome that offers women as well as their partners and families that allows women to sample their vaginal microbiome. Read more about Your Private Biome. 
• (34:59) A paper on circumcision and it’s influence on bacterial load on the penis. Read the paper. 
• (40:40) On the after show, David and Bill talk about their own health issues, specifically allergies.
• (46:15) During our conversation of Bill’s cat allergies, we mention the Kitty Microbiome. Learn more here.

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. 

The maturation of the microbiome during the first year of life

Dr. Jeffrey Gordon recently published a review article describing the importance of the proper development of the microbiome in the early stages of life.  One paper that certainly would have made it into the review if it was published in time is a new paper published last week out of Sweden and China that studied the developing microbiome of children over the course of their first year of life.

The team of scientists studied 98 women and their newborn babies. They sequenced the mother’s stool, the newborns stool, and again the child’s stool at 4 and 12 months. Throughout the study, because they used a technique called shotgun sequencing, they identified 4,000 new microbial genomes.

The infants in the study were breastfed for varying amounts of time with some never being breastfed at all. The researchers found that breastfeeding and the timeline of cessation of breastfeeding was critical to driving microbiome development. Many had previously hypothesized that it was the time at which solid foods were introduced was most important for microbiome development, however this study found that it was the time at which breastfeeding was stopped. Children that stopped breastfeeding earlier had microbiomes more similar to adults at 12 months while children who were breastfed for the duration of the study continued to have microbiomes dominated by Bifidobacterium and Lactobacillus.

The scientists also found that the 15 babies born via C-section had different microbiomes than the other 83 babies studied.  The infants born via C-section had microbiomes that more closely resembled skin and mouth microbial communities while the babies born vaginally had microbiomes more closely resembling the bacteria in their mother’s stool.

We still don’t know exactly what a “healthy” microbiome looks like and which microbial profile is best for the child. This study provides a very solid experimental design to study the development of the microbiome and allows for the continued monitoring of these children’s microbial development over the course of their lives. 

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.