Objective: To evaluate the association between the early pregnancy vaginal microbiome and spontaneous preterm birth (sPTB) and early term birth (sETB) among African American women. Methods: Vaginal samples collected in early pregnancy (8-14 weeks’ gestation) from 436 women enrolled in the Emory University African American Vaginal, Oral, and Gut Microbiome in Pregnancy Study underwent 16S rRNA gene sequencing of the V3-V4 region, taxonomic classification, and community state type (CST) assignment. We compared vaginal CST and abundance of taxa for women whose pregnancy ended in sPTB (N = 44) or sETB (N= 84) to those who delivered full term (N = 231). Results: Nearly half of the women had a vaginal microbiome classified as CST IV (Diverse CST), while one-third had CST III (L. iners dominated) and just 16% had CST I, II, or V (non-iners Lactobacillus dominated). Compared to vaginal CST I, II, or V (non-iners Lactobacillus dominated), both CST III (L. iners dominated) and CST IV (Diverse) were associated with sPTB with an adjusted odds ratio (95% confidence interval) of 4.1 (1.1, infinity) and 7.7 (2.2, infinity), respectively, in multivariate logistic regression. In contrast, no vaginal CST was associated with sETB. The linear decomposition model (LDM) based on amplicon sequence variant (ASV) relative abundance found a significant overall effect of the vaginal microbiome on sPTB (p=0.034) but not sETB (p=0.320), whereas the LDM based on presence/absence of ASV found no overall effect on sPTB (p=0.328) but a significant effect on sETB (p=0.030). In testing for ASV-specific effects, the LDM found that no ASV was significantly associated with sPTB considering either relative abundance or presence/absence data after controlling for multiple comparisons (FDR 10%), although in marginal analysis the relative abundance of Gardnerella vaginalis (p=0.011), non-iners Lactobacillus (p=0.016), and Mobiluncus curtisii (p=0.035) and the presence of Atopobium vaginae (p=0.049), BVAB2 (p=0.024), Dialister microaerophilis (p=0.011), and Prevotella amnii (p=0.044) were associated with sPTB. The LDM identified the higher abundance of 7 ASVs and the presence of 13 ASVs, all commonly residents of the gut, as associated with sETB at FDR < 10%. Conclusions: In this cohort of African American women, an early pregnancy vaginal CST III or IV was associated with an increased risk of sPTB but not sETB. The relative abundance and presence of distinct taxa within the early pregnancy vaginal microbiome was associated with either sPTB or sETB.
Postmenopausal women often suffer from vaginal symptoms associated with atrophic vaginitis. Additionally, gynecologic cancer survivors may live for decades with additional, clinically significant, persistent vaginal toxicities caused by cancer therapies, including pain, dyspareunia, and sexual dysfunction. The vaginal microbiome (VM) has been previously linked with vaginal symptoms related to menopause (i.e. dryness). Our previous work showed that gynecologic cancer patients exhibit distinct VM profiles from healthy women, with low abundance of lactobacilli and prevalence of multiple opportunistic pathogenic bacteria. Here we explore the association between the dynamics and structure of the vaginal microbiome with the manifestation and persistence of vaginal symptoms, during one year after completion of cancer therapies, while controlling for clinical and sociodemographic factors. We compared cross-sectionally the vaginal microbiome in 134 women, 64 gynecologic patients treated with radiotherapy and 68 healthy controls, and we longitudinally followed a subset of 52 women quarterly (4 times in a year: pre-radiation therapy, 2, 6 and 12 months post-therapy). Differences among the VM profiles of cancer and healthy women were more pronounced with the progression of time. Cancer patients had higher diversity VMs and a variety of vaginal community types (CTs) that are not dominated by Lactobacilli, with extensive VM variation between individuals. Additionally, cancer patients exhibit highly unstable VMs (based on Bray-Curtis distances) compared to healthy controls. Vaginal symptoms prevalent in cancer patients included vaginal pain (40%), hemorrhage (35%), vaginismus (28%) and inflammation (20%), while symptoms such as dryness (45%), lack of lubrication (33%) and dyspareunia (32%) were equally or more prominent in healthy women at baseline. However, 24% of cancer patients experienced persistent symptoms at all time points, as opposed to 12% of healthy women. Symptom persistence was strongly inversely correlated with VM stability; for example, patients with persistent dryness or abnormally high pH have the most unstable microbiomes. Associations were identified between vaginal symptoms and individual bacterial taxa, including: Prevotella with vaginal dryness, Delftia with pain following vaginal intercourse, and Gemillaceaea with low levels of lubrication during intercourse. Taken together our results indicate that gynecologic cancer therapy is associated with reduced vaginal microbiome stability and vaginal symptom persistence.
Background: Periodontal disease in pregnancy is considered a risk factor for adverse birth outcomes. Periodontal disease has a microbial etiology, however, the current state of knowledge about the subgingival microbiome in pregnancy is not well understood. Objective: To characterize the structure and diversity of the subgingival microbiome in early and late pregnancy and explore relationships between the subgingival microbiome and preterm birth among pregnant Black women. Methods: This longitudinal descriptive study used 16S rRNA sequencing to profile the subgingival microbiome of 59 Black women and describe microbial ecology using alpha and beta diversity metrics. We also compared microbiome features across early (8-14 weeks) and late (24-30 weeks) gestation overall and according to gestational age at birth outcomes (spontaneous preterm, spontaneous early term, full term). Results: In this sample of Black pregnant women, the top twenty bacterial taxa represented in the subgingival microbiome included a spectrum representative of various stages of biofilm progression leading to periodontal disease, including known periopathogens Porphyromonas gingivalis and Tannerella forsythia. Other organisms associated with periodontal disease reflected in the subgingival microbiome included several Prevotella spp., and Campylobacter spp. Measures of alpha or beta diversity did not distinguish the subgingival microbiome of women according to early/late gestation or full term/spontaneous preterm birth; however, alpha diversity differences in late pregnancy between women who spontaneously delivered early term and women who delivered full term were identified. Several taxa were also identified as being differentially abundant according to early/late gestation, and full term/spontaneous early term births. Conclusions: Although the composition of the subgingival microbiome is shifted toward complexes associated with periodontal disease, the diversity of the microbiome remains stable throughout pregnancy. Several taxa were identified as being associated with spontaneous early term birth. Two, in particular, are promising targets of further investigation. Depletion of the oral commensal Lautropia mirabilis in early pregnancy and elevated levels of Prevotella melaninogenica in late pregnancy were both associated with spontaneous early term birth.
There is a high burden of human papillomavirus (HPV) associated cancers in low- and middle-income countries (LMICs). Reducing the recommended dosing schedule from two doses to one makes the vaccine schedule logistically simpler and lowers the cost. This could make the distribution of the current vaccine supply more equitable and lead to the protection of more people. However, the clinical trials studying the efficacy of a single-dose schedule have not yet delivered final results. Against this background, the question is whether a single-dose HPV vaccine recommendation is appropriate now, and if so, what are the ethical considerations of such a recommendation? We developed three ethical recommendations: (1) adopt a holistic view of evidence to justify policy decisions; (2) prioritize the reduction in global disparities in decision-making at all levels; and (3) be transparent in the reporting of how key stakeholder interests have shaped the collection and interpretation of the evidence, and ultimate decisions. The complex discussion regarding the HPV single-dose vaccine schedule highlights the need for in-depth engagement globally to improve our understanding of country-specific contexts, and how those contexts influence decisions regarding the HPV vaccine single-dose recommendation.