Asymptomatic Bacterial Vaginosis Is Associated With Depletion of Mature Superficial Cells Shed From the Vaginal Epithelium

Abstract

Previous studies have described bacterial vaginosis (BV) as associated with increased cell-shedding from the cervicovaginal epithelium. Cell-shedding in excess of cell-proliferation is thought to decrease epithelial barrier function and increase susceptibility to infection. This study evaluated the number of shed cells in mid-vaginal smears from women with a diagnosis of symptomatic BV (sBV, n = 17), asymptomatic BV (aBV, n = 71), or no BV (n = 104) by Amsel criteria. The sBV smears contained significantly more shed cells (median 158/100X field) than no BV smears (median 91/100X field), p = 7.2e−9. However, we observed that aBV smears contained significantly fewer shed cells (median 35/100X field) than no BV smears, p = 22.0e−16. The sizes of cell-aggregates (cells shed in sometimes multilayered sections with intact cell-cell attachments) followed the same pattern. Cell-aggregates in sBV smears were significantly larger (median ∼220,000 µm 2) than those in no BV smears (median ∼50,000 µm 2), p = 1.8e−6, but cell-aggregates in aBV smears were significantly smaller (median ∼7,000 µm 2) than those in no BV smears, p = 0.0028. We also compared the superficial cell index (SCI), a measure of cervicovaginal epithelial cell maturity, in no BV and aBV smears with relatively low numbers of shed cells (≤50/100X field). The SCI of no BV smears was significantly higher (median 0.86) than that of aBV smears (median 0.35), p = 4.3e−98, suggesting a depletion of mature cells with exposure and shedding of underlying immature cells in aBV with low number of shed cells. These results indicate that aBV may contribute disproportionately to the increased susceptibility to reproductive tract infections associated with BV. Our findings remained true when considering only those smears in which the microbiota comprised a diverse set of strict and facultative anaerobic bacteria [Community State Type IV (n = 162)], thus excluding those dominated by Lactobacillus spp. This is consistent with our developing hypothesis that high-shedding sBV and low-shedding aBV could be temporally separated phases of the same condition, rather than two separate forms of BV. These findings might inform future work on clinical management of symptomatic and asymptomatic bacterial vaginosis.

Distinct Functional Traits of Lactobacilli from Women with Asymptomatic Bacterial Vaginosis and Normal Microbiota

“…With no risk of antimicrobial resistance, the use of probiotic lactobacilli as a prophylaxis for symptomatic BV appears coherent. Asymptomatic BV is also highly prevalent in women, associated with a lactobacilli-deficient condition [ 6 , 25 ] and an increased risk of infection due to disruption of the vaginal epithelium [ 26 ]. However, it is largely unknown whether the lactobacilli present during eubiosis have different functional properties than lactobacilli during asymptomatic BV.…”

Diversity of Vaginal Microbiota Affects Epithelial Barrier Permeability Among African Pregnant Women

“…The low ZO-1 proteins in the cervico-vaginal lavages of HIV-negative pregnant women with a diverse vaginal microbiota i.e. CT3 and CT4 could possibly be due to the decreased cell proliferation and differentiation as has been previously reported 30 . Women with a non-Lactobacillus dominant vaginal microbiota have a higher number of immature epithelial cells 31 which have lower expression of tight junction proteins.…”

Observational cohort study of the effect of a single lubricant exposure during transvaginal ultrasound on cell-shedding from the vaginal epithelium

“…Fibroids were a common finding on TVUS; however, there are no data relating fibroids to the vaginal epithelium. The vaginal microbiota was not evaluated, and we have previously shown that asymptomatic bacterial vaginosis (BV) is associated with the shedding of fewer, lower MI epithelial cells [15]. While menses did not appear to significantly influence our analysis and there was no association between hormonal contraception and baseline MI, we were unable to model menstrual cycle phase or specific types of hormonal contraception due to sample size limitations.…”

“…Lactic acid is a broad-spectrum bactericide and viricide [8][9][10][11], and also has a significant anti-inflammatory effect on the VE [12,13]. Detachment/shedding of the outer layer of mature cells in excess of proliferation/maturation rates will expose the underlying living cells [Fig 1C], and it has been hypothesized that this may influence susceptibility or resistence to reproductive tract infections [14,15]. The spermicide N9 causes an increase in detachment/shedding of epithelial cells that is associated with increased risk of HIV infection [16].…”