Vaginal Mucosal Homeostatic Response May Determine Pregnancy Outcome in Women With Bacterial Vaginosis: A Pilot Study

Abstract

Bacterial vaginosis (BV) is considered as a trigger for an inflammatory response that could promote adverse pregnancy outcome (APO). We hypothesized that BV-related inflammation could be counterbalanced by anti-inflammatory and mucosal homeostatic responses that could participate in pregnancy outcomes.A total of 402 vaginal self-samples from pregnant women in their first trimester were screened by Nugent score. In this population, we enrolled 23 pregnant women with BV but without APO, 5 pregnant women with BV and developing APO, 21 pregnant women with intermediate flora, and 28 random control samples from pregnant women without BV or APO.BV without APO in pregnant women was associated with 28-fold interleukin-8, 5-fold interleukin-10, and 40-fold interleukin-22 increases in expression compared to controls. BV associated with APO in pregnant women shared 4-fold increase in tumor necrosis factor, 100-fold decrease in interleukin-10, and no variation in interleukin-22 expressions compared to controls. Next-generation sequencing of vaginal microbiota revealed a shift from obligate anaerobic bacteria dominance in BV without APO pregnant women to Lactobacillus dominance microbiota in BV with APO.Our results show that the anti-inflammatory and mucosal homeostatic responses to BV may determine outcome of pregnancy in the setting of BV possibly through effects on the vaginal microbiota.

FIGURE 1

Relative gene expression of proinflammatory, mucosal homeostatic, and anti-inflammatory cytokines in the vagina pregnant women. APO = adverse pregnancy outcome, BV = bacterial vaginosis, IF = intermediate flora.

FIGURE 2

Vaginal microbiota composition of pregnant women with bacterial vaginosis but without adverse pregnancy outcome (BV-APO⁻) and pregnant women with bacterial vaginosis and developing adverse pregnancy outcome (BV-APO⁺).

FIGURE 3

Proposed underlying mechanisms of outcomes of pregnancy in the setting of bacterial vaginosis. (A) The typical microbiota observed in bacterial vaginosis (varied obligate anaerobic bacteria and limited Lactobacilli and Gardnerella) elicit a mucosal response characterized by concomitant increases in both pro- and anti-inflammatory cytokines (IL-8 and IL-10, respectively) further balanced by an increased mucosal homeostatic response (increased IL-22) when compared to controls without bacterial vaginosis. This microbiota/response profile is associated with uncomplicated pregnancy outcomes despite bacterial vaginosis. (B) Another vaginal microbiota observed in certain cases of bacterial vaginosis (predominant Lactobacilli and lacking obligate anaerobes) elicit a different mucosal response characterized by a proinflammatory imbalance (increased TNF and 100-fold decrease in IL-10) and an unchanged homeostatic mucosal response (unchanged IL-22) when compared to controls without bacterial vaginosis. This microbiota/response profile is associated with adverse pregnancy outcomes. IL = interleukin, TNF = tumor necrosis factor.