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 micro-biomes 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 immunosor-bent 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 micro-biome that optimizes reproductive health fitness, therefore reducing the incidence of preterm birth.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1-20 |
| Number of pages | 20 |
| Journal | mSphere |
| Volume | 6 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 27 2021 |
Bibliographical note
Funding Information:The study was supported by the Pan African University (PAU), a continental initiative of the African Union Commission (AU), Addis Ababa, Ethiopia, and the Center for Individualized Medicine (CIM) at the Mayo Clinic, Rochester, Minnesota, USA. N.M.O. received funding from PAU for this study. O.O.O. and A.O.O. were supported by the College of Medicine, University of Ibadan. J.C., P.J., L.Y., S.J., M.R.S.W.-A., and N.C. were supported by the Microbiome Program within CIM. M.R.S.W.-A. acknowledges support by CTSA grant number KL2 TR002379 from the National Center for Advancing Translational Science (NCATS).
Funding Information:
First and foremost, we gratefully acknowledge the participants of this study and the team of research coordinators. We also thank T. A. O. Oluwasola, Stephanie D. Song, James D. Brunner, Kevin Peterson, and O. B. Oghenetega for kind assistance and useful discussions. We thank J. E. Ifebude and R. E. M. Takpe for assistance and support toward participant recruitment. We also thank Cindy C. Jensen for critical reading of the manuscript. The study was supported by the Pan African University (PAU), a continental initiative of the African Union Commission (AU), Addis Ababa, Ethiopia, and the Center for Individualized Medicine (CIM) at the Mayo Clinic, Rochester, Minnesota, USA. N.M.O. received funding from PAU for this study. O.O.O. and A.O.O. were supported by the College of Medicine, University of Ibadan. J.C., P.J., L.Y., S.J., M.R.S.W.-A., and N.C. were supported by the Microbiome Program within CIM. M.R.S.W.-A. acknowledges support by CTSA grant number KL2 TR002379 from the National Center for Advancing Translational Science (NCATS). This paper?s contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. M.R.S.W.-A. is a member of the scientific advisory board of LUCA Biologics, Inc., on research related to urinary tract infections, preterm birth, and reproductive medicine. These activities do not overlap the research presented here. All other authors have no competing interests to disclose.
Publisher Copyright:
© 2021 Odogwu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Keywords
- Atopobium vaginae
- Nigeria
- Nigerian women
- estradiol
- estrogen
- midtrimester
- pregnancy
- preterm birth
- preterm birth risk
- progesterone
- vaginal microbiota
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
