Does the use of antibiotics for bacterial vaginosis during pregnancy reduce the risk of preterm birth?

Bacterial vaginosis (BV) is an inflammatory disease that is defined as a vaginal microbiome that is not dominated by Lactobacilli.  This abnormal vaginal flora is associated with preterm birth and miscarriage.  A recent study showed that women’s vaginal microbiomes shift frequently during pregnancy, but that the amount of time spent with a flora not dominated by Lactobacillus was associated with the length of the pregnancy, i.e. the less time spent with Lactobacillus the shorter the pregnancy.  Considering these studies, doctors may want to begin screening the vaginal microbiome during pregnancy, and treating BV (which is currently done through antibiotics).  Strategies such as that one have not yet been rigorously studied, so their efficacy is still unknown.  Last week a study out of Japan performed a study that showed little improvement in preterm birth risk by monitoring and treating BV during pregnancy.  The results were published in Nature Scientific Reports.

The researchers measured the microbiomes of 1,735 pregnant women and split them into two groups.  Women in the intervention group that had BV were given antibiotics, whereas women in the control group, whether they had BV or not, proceeded as normal through their pregnancy.  Women in both groups had their vaginal microbiomes sampled at various time points throughout the pregnancy. The first group would have their BV status verified, and placed on antibiotics. In both groups, approximately 10% of the women had preterm birth at around 30 weeks gestational age.  There was no significant difference in these rates between the two groups, meaning that administration of antibiotics did not appear to prevent preterm birth.  Even though the antibiotics did not prevent preterm birth, the researchers noted that regardless of group, women who entered preterm birth did have abnormal vaginal flora compared to women who went full term, supporting the notion that BV is highly correlated with preterm birth.  They noted that many of the women who entered preterm labor did not have BV at the initial time of screening, but acquired BV at some point during pregnancy. 

This paper supports the idea that BV may cause preterm birth, however it cannot recommend universal screening for BV in pregnant women for two reasons.  First, the antibiotics did not appear to affect the rates of preterm birth, and second many of the women who had preterm birth only had abnormal flora after initial screening.  Perhaps a better strategy would be to constantly monitor BV status throughout pregnancy.  In addition, there will soon be healthier and more effective methods to treat BV than antibiotics, which are only shown to have a transient effect on BV and disrupt the rest of the microbiome.

Our gut microbiome may be contributing to some forms of blindness

Our eyes are considered ‘immune privileged’, which means that they are generally protected from our own immune system.  The major mechanism for eye immune privilege comes from a tight physical barrier that separates our lymphocytes, such as T cells, from the actual eye.  T cells do have the ability to cross this barrier, but they first must come in contact with, and be activated by eye antigens.  These antigens are sequestered on the opposite side of the barrier, in the eye, so that they are not exposed to the T cells.  There are diseases in which these retinal T cells do mysteriously become activated though, and they cause an inflammatory disease known as uveitis.  Uveitis is responsible for causing blindness and other eye issues in many people, but again the cause for the T cell activation is largely unknown.  Researchers at the NIH recently created a mouse model for uveitis, and were able to test a variety of factors that may be activating the T cells.  To their surprise, the gut microbiota seemed to be activating the T cells.  They published the results of their study last week in the journal Immunity.

The researchers first created a mouse model of uveitis where the retinal T cells spontaneously become activated.  They then noticed that the highest concentration of these T cells were near the gut, suggesting the gut bacteria were playing a role.  The scientists then treated the mice with antibiotics to decrease the gut bacterial concentration.  Although the mice still developed some symptoms of uveitis, the disease was ameliorated greatly in these mice.  As previously discussed, the normal T cell activator antigen is in the and physically separated.  In order to ensure that this antigen wasn’t somehow leaking out of the eye to activate the T cells in their model they created mice that lacked these antigens in their eye.  Still though, the mice presented symptoms of uveitis, meaning that the antigen that is activating the T cells is not from the eye, but rather is being produced somewhere else, such as the gut.  In order to firmly prove the gut bacteria’s role, the scientists showed that T cells could be activated by specific proteins from gut bacteria.  In fact, germ free mice, which otherwise would not have an ocular inflammatory response in their model, showed strong uveitis when they were given just the protein extract from other wild type mice. 

This research is the first to connect the gut microbiome with ocular autoimmune inflammation.  It presents many questions as to how to therapeutically combat this disease, perhaps through monitoring the gut microbiota for presentation of antigens that could activate these retinal T cells.  It also begs to be connected with other sites immune privilege breakdown in the body.  The fetus and placenta in pregnant women, for example, is an immune privileged space.  Immune activation of this site can sometimes lead to miscarriage.  Are gut or vaginal bacteria involved with this response, as we have discussed a few times in this blog?  In time, scientists will know enough to accurately answer this question.

Vaginal microbiome once again tied to preterm birth

Preterm birth is major global health challenge.  Today, around 11% of all babies are born prior to 37 weeks, and are considered preterm.  Many of the causes of these preterm births are still unknown, but it is thought that around 25% of them may be related to a bacterial infection that comes from somewhere in the mother’s own body, i.e. her microbiome.  Many studies are now linking specific vaginal bacteria to risk of preterm birth, and other studies have even shown a connection between other microbiome sites, such as the gut and oral microbiome.  Unfortunately, studies on the microbiome and preterm birth are extremely difficult to conduct, so there are just not enough to have any sort of scientific consensus on the topic.  Last week though, a very rigorous study out f Stanford University was published in the Proceedings of the National Academy of Sciences that monitored expectant mothers vagina, gut, and oral microbiome throughout the course of her pregnancy and then for one year after.  Among many interesting findings, which are discussed below, the most important one was yet another connection between bacterial vaginosis and preterm birth.

The researchers monitored the vaginal, distal gut, salivary, and tooth/gum microbiomes of 49 women, 15 of which ended up delivering preterm, over the course of their pregnancy and for one year after.  Interestingly, the non-vaginal sites’ microbiomes remained relatively stable over the duration of the pregnancy, and even for the one year after.  The vaginal microbiome, however, did show some differences during and after pregnancy.

As many of our readers already know, a healthy vaginal flora is dominated by Lactobacilli, but around 20% of American women are dominated by other species, such as Gardnerella vaginalis, and have an overall increased vaginal diversity.  These women have what is known as community state type four, or CST4, and these women could be diagnosed with bacterial vaginosis (BV), though the clinical diagnosis is not so specific.  The other community state types, CST1, 2, 3, and 5, are dominated by different strains of Lactobacilli, and are generally regarded as healthy.  This current research showed that many of the women’s vaginal microbiomes actually shifted between various CST’s during pregnancy, most often shifting to and from CST4.  These transitions had no association with preterm birth, though.  After giving birth the vaginal microbiome became more diverse, and had greater abundances in anaerobic bacteria, such as Peptoniphilus, Prevotella, and Anaerococcus.  In addition, this usually coincided with a decrease in Lactobacilli.  Surprisingly, these changes did not seem to relate to mode of delivery (C-section of vaginal).

CST4 has been linked to preterm birth before, and this was reinforced in this study.  The scientists found that the longer a women’s vaginal microbiome was within CST4, the greater risk she had for preterm birth.  In addition, the abundance of Gardnerella and Ureaplasma, specifically, were linked to preterm birth.

This study reinforces what many microbiome scientists already suspect, and that is the importance of the vaginal flora in preterm birth.  It is unclear at this point if manipulating the vaginal flora prior to, or during pregnancy would help prevent preterm birth, but it is certainly worthy of discussion and clinical testing.  If you are reading this and wondering what your vaginal microbiome is, then we recommend you participate in the citizen science project, YourPrivateBiome, to find out.  You can learn more about it by following this link on our site, or just click the link above.

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.