Abstract

Recent studies suggest that birth mode (Cesarean section [C-section] or vaginal delivery) is an important event in the initial colonization of the human microbiome and may be associated with long-term health outcomes. We sought to determine the association between a woman's birth mode and her vaginal microbiota in adulthood. We re-contacted 144 adult women from two U.S. studies and administered a brief survey. Vaginal microbiota was characterized on a single sample by amplicon sequencing of the V3-V4 hypervariable regions of the 16S rRNA gene and clustered into community state types (CSTs). We evaluated the association between birth mode and a CST with low relative abundance of Lactobacillus spp. ("molecular bacterial vaginosis" [Molecular-BV]) compared to Lactobacillus-dominated CSTs in logistic regression modeling which adjusted for body mass index, a confounder in this analysis. Twenty-seven women (19%) reported C-section. Overall, C-section showed a non-significant trend towards increased odds of Molecular-BV (aOR = 1.22, 95% CI: 0.45, 3.32), and Prevotella bivia was the strongest single taxa associated with C-section. However, because the two archived studies had different inclusion criteria (interaction p = 0.048), we stratified the analysis by study site. In the study with a larger sample size (n = 88), women born by C-section had 3-fold higher odds of Molecular-BV compared to vaginally-delivered women (aOR = 3.55, p = 0.06, 95% CI: 0.97-13.02). No association was found in the smaller study (n = 56, aOR = 0.19, p = 0.14, 95% CI: 0.02-1.71). This pilot cross-sectional study suggests a possible association between C-section and Molecular-BV in adulthood. However, the analysis is limited by small sample size and lack of comparability in participant age and other characteristics between the study sites. Future longitudinal studies could recruit larger samples of women, address the temporal dynamics of vaginal microbiota, and explore other confounders, including maternal factors, breastfeeding history, and socioeconomic status, which may affect the relationship between birth mode and vaginal microbiota.

Highlights

  • There is emerging evidence that babies born by Cesarean section (C-section) are more likely to develop metabolic and chronic disorders, including celiac disease, diabetes mellitus, obesity, food allergy, and asthma, in early childhood, compared to those born by vaginal delivery.[1,2,3,4,5,6,7] In addition, the association between C-section delivery and obesity has been shown to persist into adolescence and adulthood.[8]

  • Among women recruited from the Hormonal Contraception Longitudinal (HCL) study, being born by C-section was associated with a 3-fold increase in the odds of having the low-Lactobacillus community state types (CSTs) IV (Molecular-bacterial vaginosis (BV)) at a single time point in adulthood

  • P. bivia, a species often found in CST IV, was the bacterial taxon most strongly associated with birth mode, with higher relative abundances more often observed among C-section-delivered women

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Summary

Introduction

There is emerging evidence that babies born by Cesarean section (C-section) are more likely to develop metabolic and chronic disorders, including celiac disease, diabetes mellitus, obesity, food allergy, and asthma, in early childhood, compared to those born by vaginal delivery.[1,2,3,4,5,6,7] In addition, the association between C-section delivery and obesity has been shown to persist into adolescence and adulthood.[8]. Reproductive-age women with Lactobacillus-dominated vaginal microbiota are at lower risk for bacterial vaginosis (BV), which reduces the likelihood of sexually transmitted infection (STI) acquisition and development of abnormal pregnancy outcomes.[12] While there are a number of studies on demographic and behavioral risk factors for BV in adult women [13,14,15,16], less is known about the early risk factors for BV. We hypothesized that a woman’s birth mode, that is, the method through which she was delivered by her mother, is an important early life factor in determining how a woman’s vaginal microbiota is initially seeded and transitions into adulthood. Any differences in the composition of vaginal microbiota attributable to birth mode must persist through known hormonally-driven transitions in the microbiota during early childhood and puberty, including the longitudinal dynamics observed among reproductive-age women in menstruation and pregnancy

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