Lactobacillus crispatus thrives in pregnancy hormonal milieu in a Nigerian patient cohort.

Steroid hormones are one of the presumed modulators of Lactobacillus abundance in the vaginal epithelium. We set out to characterize the vaginal microbiome (VMB) and also provide an in-depth understanding of the relative contribution of estradiol (E2) and progesterone (P1) in shaping the vaginal microbiome of Nigerian women (n = 38) who experienced both uncomplicated term delivery and preterm delivery using samples longitudinally collected during pregnancy (17-21, 27-31, 36-41 weeks gestation) and 6 weeks postpartum. Vaginal swabs and blood samples were aseptically collected. Vaginal swabs were used for microbiome assessment using 16S ribosomal RNA (rRNA) gene sequencing. Blood samples were used for hormonal measurement using a competitive-based enzyme-linked immunosorbent assay (ELISA). Across several maternal covariates, maternal age, pregnancy status and delivery mode were not significantly associated with the vaginal microbiota whereas maternal E2 level (pE2 = 0.006, Omnibus), and P1 level (pP1 = 0.001, Omnibus) were significantly associated with the vaginal microbiome. E2 and P1 concentrations increased throughout pregnancy commensurately with increasing proportions of L. crispatus (pE2 = 0.036, pP1 = 0.034, Linear Mixed Model). An increasing trend of α-diversity was also observed as pregnancy progressed (pobserved ASV = 0.006, LMM). A compositional microbiome shift from Lactobacillus profile to non-Lactobacillus profile was observed in most postnatal women (pCST IV < 0.001, LMM). Analysis of our data shows a species-specific link between pregnancy steroid hormone concentration and L. crispatus abundance.

Predominance of Atopobium vaginae at Midtrimester: a Potential Indicator of Preterm Birth Risk in a Nigerian Cohort.

Preterm birth (PTB) is the largest contributor to infant death in sub-Saharan Africa and globally. With a global estimate of 773,600, Nigeria has the third highest rate of PTB worldwide. There have been a number of microbiome profiling studies to identify vaginal microbiomes suggestive of preterm and healthy birth outcome. However, studies on the pregnancy vaginal microbiome in Africa are sparse with none performed in Nigeria. Moreover, few studies have considered the concurrent impact of steroid hormones and the vaginal microbiome on pregnancy outcome. We assessed two key determinants of pregnancy progression to gain a deeper understanding of the interactions between vaginal microbiome composition, steroid hormone concentrations, and pregnancy outcome. Vaginal swabs and blood samples were prospectively collected from healthy midtrimester pregnant women. Vaginal microbiome compositions were assessed by analysis of the V3-V5 region of 16S rRNA genes, and potential functional metabolic traits of identified vaginal microbiomes were imputed by PICRUSt (phylogenetic investigation of communities by reconstruction of unobserved states) analysis, while plasma estradiol (E2) and progesterone (P1) levels were quantified by the competitive enzyme-linked immunosorbent assay (ELISA). PTB vaginal samples were characterized by increased microbial richness, high diversity, and depletion of lactobacilli compared to term delivery samples. Women who delivered preterm were characterized by an Atopobium vaginae-dominated vagitype. High relative abundance of Atopobium vaginae at the midtrimester was highly predictive of PTB (area under the receiving operator characteristics [AUROC] of 0.983). There was a marked overlap in the range of plasma E2 and P1 values between term and PTB groups.IMPORTANCE Giving birth too soon accounts for half of all newborn deaths worldwide. Clinical symptoms alone are not sufficient to identify women at risk of giving birth too early, as such a pragmatic approach to reducing the incidence of preterm birth entails developing early strategies for intervention before it materializes. In view of the role played by the vaginal microbiome and maternal steroid hormones in determining obstetric outcome, we assessed the vaginal microbiome composition and steroid hormone during pregnancy and examined their relationship in predicting preterm birth risk in Nigerian women. This study highlights a potential early-driver microbial marker for prediction of preterm birth risk and supports the notion that vaginal microbiome composition varies across populations. A knowledge of relevant preterm birth microbial markers specific to populations would enhance the development of personalized therapeutic interventions toward restoring a microbiome that optimizes reproductive health fitness, therefore reducing the incidence of preterm birth.