The vaginal microbiome changes during and after pregnancy

The vaginal microbiome is critically important to a healthy pregnancy, and studies have shown that vaginal dysbiosis during pregnancy can lead to infection and preterm birth.  In order to help understand what the microbiome looks like throughout and just after pregnancy, researchers from England performed longitudinal studies on 42 pregnant women.  They published their results last week in Nature Scientific Reports.

The scientists sequenced the microbiomes of the 42 women throughout their pregnancies, and then for the 6 weeks afterwards for some of the women.  They discovered, in agreement with other literature on the subject, that the vaginal microbiome becomes dominated by Lactobacilli species during pregnancy.  The Lactobacilli are thought to prevent pathogens from colonizing the vagina because they produce lactic acid which decreases the overall pH of the vagina, and they secrete antibacterial toxins.  These Lactobacilli are also important as they are normally the first to colonize the new infants' guts after they pass through the birth canal. 

The researchers also learned that the microbiome shifts away from Lactobacilli and towards a more diverse microbiome in the period immediately following birth.  The new bacteria that colonize are often associated with vaginosis, and these can lead to inflammation and infection of the birth canal in some women.  The scientists suspect this shift occurs because there is a sudden drop in estrogen production upon removal of the placenta.  The increase in circulating estrogen is thought to be important for Lactobacilli colonization, so it makes sense that the rapid decrease in estrogen decreases Lactobacilli abundance.

Finally, this study showed that there were geographic and ethnic variations to the pregnant microbiome.  While each microbiome was associated with a healthy pregnancy, there were important differences, especially on the species level.  For example, Asian and Caucasian women’s pregnant microbiomes were dominated by Lactobacillus gasseri, while this species was absent in black women’s pregnant microbiomes.

This paper helps show the normal progression of the microbiome during and after pregnancy.  With the mounting evidence that the microbiome is often a contributing factor to preterm birth and some post-partum diseases, papers like this one are important to some day discovering the mechanistic basis for our microbiome's association with these issues. 

Vaginal microbiome during pregnancy. iHMP blog #2

Gardnerella Vaginalis, a bacteria associated with spontaneous preterm labor.

The vaginal microbiome undergoes many changes during pregnancy, and it has been associated with various afflictions, such as gestational diabetes, low birth weight, necrotizing enterocolitis, and colic.  In addition, infection of the uterine cavity is correlated with preterm labor, especially for early preterm labor.  For now though, the crucial role of the microbiome during pregnancy remains largely unknown.

The iHMP will define the  healthy pregnancy microbiome, and investigate how deviations from the healthy microbiome may contribute to preterm birth and still birth.  The iHMP will do a longitudinal study (study spanning the length of the pregnancy and some time after) of 2,000 women, some of whom will be at risk for preterm birth.  The women will have their entire microbiomes, not just vaginal microbiomes, examined regularly during the course of pregnancy and thereafter.  Other microbiome samples include the placenta, amniotic fluid, umbilical cord, and the child's microbiome as well.  This study will measure bacteria, lipids, cytokines, and proteins, which have all been associated with pregnancy disorders.  The cohort will consist of women who are racially diverse and have a wide range of ages.

One of the motivations for this project was a study published in the New England Journal of Medicine in 2000 that reviewed intrauterine infection and its link to preterm birth.  Preterm birth is most often caused by spontaneous labor or rupture of membranes, and is highly correlated with infection.  For more information, follow the link above.

The human microbiome project, part 2. iHMP blog #1

The human microbiome project (HMP) was a large scale program sponsored by the NIH's common fund, which sought to define the healthy human microbiome.  The HMP was a success, and its main findings serve as a foundation upon which most microbiome science is built (cited almost 700 times in 2 years!). Perhaps it was the unexpected successor to the human genome project (HGP), but it is already nearing the HGP in influence.  

Because of its success the NIH is sponsoring the human microbiome project 2 (HMP2), otherwise known as the integrative human microbiome project (iHMP).  Where HMP1 investigated what the human microbiome looked like, iHMP is looking at how the human microbiome is associated with various "exemplars of microbiome-associated human conditions".  

These three conditions are:

1) "Pregnancy, including those that end in preterm birth"
2) "Gut disease onset, using inflammatory bowel disease (IBD) as a model"
3) "Respiratory viral infection and onset of type 2 diabetes (T2D)"

iHMP will track large cohorts of individuals for each of these conditions for 3 years to perform complete longitudinal studies.  Many variables and data sets will be tracked, compiled, and made public.  Of course bacteria will be sampled, but, for the first time, comprehensive sampling of metabolites from those bacteria will also be performed. The results of iHMP will be published periodically and will last from 2013 to 2016.

We would like to thank the entire HMP consortium of scientific investigators for their efforts, but especially Lita Proctor, who has championed the microbiome within the NIH for many years.  Her perspective on iHMP, which was recently published in Cell, was the basis for this blog post and from where the quotations are drawn.

We will will kick off a 3 part blog series here on the AMI blog where I review the 3 microbiome conditions that are being studied in the iHMP.  Check back on Monday for a post discussion about how the microbiome is associated with pregnancy, and how the iHMP plans to perform its investigation.

Pregnancy and the microbiome

There have been a number of studies that discuss the importance of the microbiome transfer between mother and child; however few studies have looked into the changes that occur to the mother's vaginal microbiome during pregnancy.

A new paper published in the journal Microbiome by AMI Scientific Advisory Board member Dr. Jacques Ravel of the University of Maryland School of Medicine presents a longitudinal study of the vaginal microbiome of women during the course of pregnancy and compared that with women who were not pregnant.  The overall findings of the study conclude that there are statistically significant differences in the vaginal bacterial populations between pregnant and non-pregnant women.  Furthermore, the microbiome of pregnant women was more stable in non-pregnant women.

While there is a difference in the microbiome between pregnant and non-pregnant women, the authors stress that this difference in microbiomes may NOT be exclusive to pregnancy; therefore  at this point, not suitable for diagnostic purposes (say determining pregancy).  Furthermore, it is not known if these differences in any way benefit pregnant women or are just the result of different vaginal environments, for example higher estrogen levels in the vagina.

Finally, another paper that was possibly from the same longitudinal study showed no statistical connection between the vaginal microbiomes of women who go into pre-term labor and those who carry their child full term.