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

Abstract

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.

Vaginal Dysbiotic Microbiome in Women With No Symptoms of Genital Infections

“…Aromatic amino acid biosynthesis, carbohydrate degradation, pentose phosphate pathway that may cause preterm birth were enriched in asymptomatic BV women. Women who gave preterm birth had a vaginal microbiome enriched with the nonoxidative branch of the pentose phosphate pathway ( Odogwu et al., 2021 ). Thus, functionally, many of the enriched BV pathways were also reflective of vaginal microbiota associated with preterm birth.…”

“…Reproductive Tract Infections (RTIs) caused by bacteria, viruses or protozoa have a profound impact on the reproductive and sexual health of men and women. The consequences of sexually transmitted infections/reproductive Tract Infections (STIs/RTIs) for reproductive health include pelvic inflammatory disease (PID), infertility (in women and men), ectopic pregnancy, and adverse pregnancy outcomes including miscarriage, stillbirth, preterm birth, and congenital infection ( Mullick et al., 2005 ; Odogwu et al., 2021 ). STIs and RTIs are also known to increase the risk of HIV transmission ( Taha and Gray, 2000 ; van de Wijgert et al., 2008 ; Ward and Rönn, 2010 ).…”

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

“…in the vaginal microbiota delivered preterm as also reported in previous studies 7 , 22 , 58 , 59 . In particular, Atopobium (CST IV) remained persistent throughout pregnancy in women who delivered preterm, buttressing a cause-effect relationship between Atopobium and preterm birth 7 , 60 – 62 . Our data further reveal that the vaginal microbiome of Nigerian women was typically dominated by L. iners .…”

Vaginal Atopobium is Associated with Spontaneous Abortion in the First Trimester: a Prospective Cohort Study in China

“…Members of the genus Atopobium are commonly found in the vaginas of women, with 97% of these being A. vaginae ( 30 ), a Gram-positive, strict anaerobe that produces major amounts of lactic acid ( 31 ). This kind of bacteria has been considered a common component of the vaginal microbiome, but a series of studies found that Atopobium in the female genital tract is associated with different female reproductive disorders; for example, an A. vaginae – dominated vagitype was observed in pregnant women who delivered preterm babies in a Nigerian cohort ( 32 ), and women at high risk of preterm birth were identifiable by a high vaginal load of A. vaginae (DNA level ≥ 108 copies/mL) ( 33 ). Second, previous study has suggested Atopobium to be one of the significantly more abundant genera associated with recurrent spontaneous abortion ( 34 ).…”