Dysbiotic Vaginal Microbiota Induces Preterm Birth Cascade via Pathogenic Molecules in the Vagina.
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ABSTRACT:
SUBMITTER: Ansari A
PROVIDER: S-EPMC10821287 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Dysbiotic Vaginal Microbiota Induces Preterm Birth Cascade via Pathogenic Molecules in the Vagina.
Ansari AbuZar A You Young-Ah YA Lee Gain G Kim Soo Min SM Park Sun Wha SW Hur Young Min YM Kim Young Ju YJ
Metabolites 20240111 1
Dysbiotic vaginal microbiota (DVM) disturb the vaginal environment, including pH, metabolite, protein, and cytokine profiles. This study investigated the impact of DVM on the vaginal environment in 40 Korean pregnant women and identified predictable biomarkers of birth outcomes. Cervicovaginal fluid (CVF) samples were collected in the third trimester using vaginal swabs, examined for pH, and stored at -80 °C for further analysis. The samples were grouped as full-term (FTB, n = 20) and preterm (P ...[more]
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Project description:BackgroundDespite decades of attempts to link infectious agents to preterm birth, an exact causative microbe or community of microbes remains elusive. Nonculture 16S ribosomal RNA gene sequencing suggests important racial differences and pregnancy specific changes in the vaginal microbial communities. A recent study examining the association of the vaginal microbiome and preterm birth documented important findings but was performed in a predominantly white cohort. Given the important racial differences in bacterial communities within the vagina as well as persistent racial disparities in preterm birth, it is important to examine cohorts with varied demographic compositions.ObjectiveTo characterize vaginal microbial community characteristics in a large, predominantly African-American, longitudinal cohort of pregnant women and test whether particular vaginal microbial community characteristics are associated with the risk for subsequent preterm birth.Study designThis is a nested case-control study within a prospective cohort study of women with singleton pregnancies, not on supplemental progesterone, and without cervical cerclage in situ. Serial mid-vaginal swabs were obtained by speculum exam at their routine prenatal visits. Sequencing of the V1V3 region of the 16S rRNA gene was performed on the Roche 454 platform. Alpha diversity community characteristics including richness, Shannon diversity, and evenness as well as beta diversity metrics including Bray Curtis Dissimilarity and specific taxon abundance were compared longitudinally in women who delivered preterm to those who delivered at term.ResultsA total of 77 subjects contributed 149 vaginal swabs longitudinally across pregnancy. Participants were predominantly African-American (69%) and had a preterm birth rate of 31%. In subjects with subsequent term delivery, the vaginal microbiome demonstrated stable community richness and Shannon diversity, whereas subjects with subsequent preterm delivery had significantly decreased vaginal richness, diversity, and evenness during pregnancy (P < .01). This change occurred between the first and second trimesters. Within-subject comparisons across pregnancy showed that preterm birth is associated with increased vaginal microbiome instability compared to term birth. No distinct taxa were associated with preterm birth.ConclusionIn a predominantly African-American population, a significant decrease of vaginal microbial community richness and diversity is associated with preterm birth. The timing of this suppression appears early in pregnancy, between the first and second trimesters, suggesting that early gestation may be an ecologically important time for events that ordain subsequent term and preterm birth outcomes.
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Project description:BackgroundDespite decades of attempts to link infectious agents to preterm birth, an exact causative microbe or community of microbes remains elusive. Culture-independent sequencing of vaginal bacterial communities demonstrates community characteristics are associated with preterm birth, although none are specific enough to apply clinically. Viruses are important components of the vaginal microbiome and have dynamic relationships with vaginal bacterial communities. We hypothesized that vaginal eukaryotic DNA viral communities (the "vaginal virome") either alone or in the context of bacterial communities are associated with preterm birth.ObjectiveThe objective of this study was to use high-throughput sequencing to examine the vaginal eukaryotic DNA virome in a cohort of pregnant women and examine associations between vaginal community characteristics and preterm birth.Study designThis is a nested case-control study within a prospective cohort study of women with singleton pregnancies, not on supplemental progesterone, and without cervical cerclage in situ. Serial midvaginal swabs were obtained at routine prenatal visits. DNA was extracted, bacterial communities were characterized by 16S ribosomal RNA gene sequencing, and eukaryotic viral communities were characterized by enrichment of viral nucleic acid with the ViroCap targeted sequence capture panel followed by nucleic acid sequencing. Viral communities were analyzed according to presence/absence of viruses, diversity, dynamics over time, and association with bacterial community data obtained from the same specimens.ResultsSixty subjects contributed 128 vaginal swabs longitudinally across pregnancy. In all, 24 patients delivered preterm. Participants were predominantly African American (65%). Six families of eukaryotic DNA viruses were detected in the vaginal samples. At least 1 virus was detected in 80% of women. No specific virus or group of viruses was associated with preterm delivery. Higher viral richness was significantly associated with preterm delivery in the full group and in the African American subgroup (P = .0005 and P = .0003, respectively). Having both high bacterial diversity and high viral diversity in the first trimester was associated with the highest risk for preterm birth.ConclusionHigher vaginal viral diversity is associated with preterm birth. Changes in vaginal virome diversity appear similar to changes in the vaginal bacterial microbiome over pregnancy, suggesting that underlying physiology of pregnancy may regulate both bacterial and viral communities.
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