The Microbiome in Women’s Health & Fertility

GREGORY BUCK

Presentation Title
The Vaginal Microbiome, Women’s Health, and Pregnancy

Abstract
The microbiota of the the female reproductive tract are believed to have a significant impact on
women’s reproductive health and pregnancy, including risk of preterm birth (PTB). Bacterial Vaginosis
affects approximately 1 of 3 women, and a complex microbiome is associated with higher risk of
infection by and transmission of sexually transmitted diseases, viral diseases including HIV, and
preterm birth (PTB) and other adverse pregnancy outcomes. Preterm PTB occurs in >10% of
pregnancies, although some populations, and in particular women of African ancestry, bear a higher
burden of risk. Most adverse outcomes of pregnancies, including neonatal death have recently
declined, but the incidence of PTB has not, and gains in understanding its fundamental etiology have
been sparse. However, it is generally agreed that a significant fraction of preterm births have a
microbial cause. With support from both phases of the NIH Human Microbiome Project, we have
sampled the vaginal microbiomes of over 6,000 women, ~1000 pregnant, in a cross sectional study,
and, collaboration with our colleagues at the Global Alliance to Prevent Prematurity and Stillbirth in
Seattle, WA, ~1500 pregnancies in a longitudinal multi omic project. Our analysis of these samples
shows that the vaginal microbiome stabilizes during pregnancy, in general in a more Lactobacillus-
dominated profile, that this occurs early in pregnancy and is largely complete by the second trimester.
These changes result in a simplification of the metabolic capacity of the vaginal microbiota, and a
general reduction in predominance of taxa usually considered less favorable. In our cross sectional
cohort of 613 pregnant and 1969 non-pregnant women and our longitudinal cohort of 90 pregnant
women, these changes were more pronounced in women of African ancestry. Women of European
ancestry generally exhibited less dramatic changes, as their vaginal microbiomes tend to be more
Lactobacillus-dominated even early in pregnancy. Our longitudinal analysis of a third cohort of 45
women who experienced preterm birth and 90 case-matched controls, identified a panel of non-
Lactobacillus taxa associated with risk of preterm birth. As expected from the observations that
vaginal microbiomes become more Lactobacillus rich as pregnancy progresses, these taxa were
more evident early in pregnancy and signal was lost by the second trimester. Women who delivered
at term showed a strong negative correlation between L. crispatus and taxa associated with dysbiosis
and PTB, and proinflammatory cytokines were generally correlated with each other and with taxa
identified as associated with PTB. In the context of other studies, ours differs in focusing largely on a
cohort of women of African ancestry, in excluding all but spontaineous preterm births, and in the
larger number of women in our cohort. This study suggests that the microbiome profiles, early in
pregnancy, may provide useful information more accurate identification of women at higher risk for
premature delivery. However, additional studies with larger case-matched cohorts will be required to
optimize these approaches.

This work was supported by NIH Common Fund Human Microbiome Project program
(1UH2/UH3AI08326 and 8U54HD080784 to GAB, KKJ and JFS), the Global Alliance to Prevent
Prematurity and Stillbirth (PPB Grant 15011) to GAB and JMF, and NIH grant 1R01HD092415 to
GAB. We thank the members of the Vaginal Microbiome Consortium at VCU (vmc.vcu.edu) for their
contributions to this project. These studies were reviewed and approved by the Virginia
Commonwealth University Institutional Review Board at (IRB# HM12169 or HM15527).

 


 

INMACULADA MORENO

Presentation Title
Role of Lactobacillus in Human Reproduction

Abstract
The discovery of microbial communities inhabiting the whole female reproductive tract has challenged
the traditional view of human fetal development in a sterile environment. Technical advances have
facilitated the study of the bacterial microbiome in the upper and lower genital tract, as well as the role
of such bacteria in women’s health and fertility. The microbiota in the urogenital tract of healthy
reproductive age women is mainly composed of bacteria from the Lactobacillus genus; however,
structural or compositional variations of this microbiota, that could occur throughout a women’s life in
response to intrinsic and extrinsic factors may impact the function of reproductive organs leading to
infertility or other pathological conditions.

 


 

AHINOAM LEV-SAGIE

Presentation Title
Vaginal Microbiome Transplantation in Women with Intractable Bacterial Vaginosis

Abstract
Bacterial Vaginosis (BV) is a form of vaginal microbial community alteration, prevalent in women of
reproductive age, affecting from one-fourth to one-third of women worldwide. It ranges from an
asymptomatic finding in most cases, to a clinically symptomatic entity characterized by an abnormal,
often malodorous vaginal discharge in 16% of the women diagnosed with BV. BV is associated with a
risk of upper genital tract infection, complications of pregnancy, and of susceptibility to sexually
transmitted infections (STI). At the clinically-severe end of the BV spectrum, treatment with antibiotics
(either systemic or vaginal) is associated with a high relapse rate. Therapeutic options are very limited
to the subpopulation of women who experience persistent or recurrent BV despite multiple antibiotic
treatment attempts. In this presentation, the use of vaginal microbiome transplantation (VMT) from
healthy donors as a therapeutic alternative for patients suffering from symptomatic, intractable and
recurrent bacterial vaginosis will be discussed. Our favourable results of VMT will be presented, and
possible future applications of VMT will be reviewed.

 


 

INA SCHUPPE-KOISTINEN

Presentation Title
Microbes and Female Reproductive Health: Population-based Studies in Sweden

Abstract
This talk will describe the ongoing large-scale studies initiated by the Centre for Translational
Microbiome Research at the Karolinska Institutet in Stockholm to characterize the role of the
microbiome in women’s health. The research questions addressed include the definition of a healthy
vaginal microbiome in a Swedish population, the association to fertility and pregnancy complications
and the role of the vaginal microbiota in the development of cervical cancer. In addition, the question
if microbiome acquisition starts in utero will be addressed.

 


 

CHRISTINE LADLINGER-SCHUBERT

 

Presentation Title
New Bacteriophage-based Therapy for the Treatment of Bacterial Vaginosis

Abstract
Bacterial vaginosis (BV) is the most common vaginal disorder worldwide in women of the
reproductive age and is associated with the increased risk of upper reproductive tract
infections, adverse pregnancy outcomes, and high susceptibility to sexually transmitted
infections. Currently antibiotics are the mainstay of therapy for BV, however, the
recurrence rate is up to 70 % within a year. BV is characterized by a microbial imbalance of
the vaginal flora, predominantly the loss of normally dominant Lacobacilli and the
overgrowth of anaerobic bacteria. More than a dozen bacterial species have been
identified to be associated with BV, among them species of the genus Gardnerella were
found to be the most prevalent, and without them BV symptoms seem not to occur.
PhagoMed isolated a panel of bacteriophage endolysins, highly evolved hydrolytic
enzymes, that specifically degrade the bacterial cell wall of all tested species within the
genus Gardnerella. By genetic engineering the lytic activity of these endolysins was further
enhanced whereat the specificity for Gardnerella spp. was still preserved. When testing
these endolysins on different Lactobacilli strains their viability was not affected.
This combination of high selectivity as well as high effectiveness in killing Gardnerella
makes endolysins a very attractive alternative to antibiotics for the treatment of BV.

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