Vaginal Microbiota and Mucosal Immune Markers in Women With Vulvovaginal Discomfort

Abstract

Background: Up to 30% of women with vaginal symptoms are not assigned a diagnosis after standard diagnostic assessment.

Methods: We compared premenopausal women with idiopathic vaginitis (IV) or vulvodynia (VVD) to healthy controls. Microbiota were characterized using rRNA sequencing. Cytokines/chemokines (IL-10, IL-1α, IL-1β, IL-6, IL-8, IL-2, IL-18, IL-4, IL-9, and IL-13) were measured in vaginal lavage fluid using the Meso Scale Discovery platform or ELISA (IL-1ra). Immunoglobulins were measured in vaginal lavage fluid using a bead-based immunoassay (Millipore). Cases and controls were compared using Kruskal-Wallis, analysis of variance, and linear regression or (for microbiome composition) the Bray-Curtis dissimilarity statistic.

Results: We compared 20 women with IV, 30 with VVD, and 52 controls. Most (80%) had greater than 90% 16S rRNA gene sequences from Lactobacillus crispatus, L. jensenii, L. gasseri, or L. iners. In analyses adjusted for age and hormonal contraception (HC), Gardnerella vaginalis was less prevalent and abundant in women with VVD (2/30, 7%) versus controls (16/52, 31%) or IV (5/20, 25%) (P = 0.030). Bray-Curtis dissimilarity was not significantly different between IV and controls or VVD. Fungal sequences were only detected in 5 participants: 2 control, 1 IV, 2 VVD. In univariate analysis, cytokines were not associated with diagnosis. Median vaginal concentration of IgE (but not other immunoglobulins) was lower in women with VVD (P = 0.006).

Conclusions: Minimal differences in vaginal microbiota and inflammatory markers between women with IV, VVD or controls suggest no striking association between vaginal bacteria, fungi or inflammation and diagnosis in these women.

Figures

Figure 1:

Relative abundance of 20 most commonly detected taxa. Participants were grouped according to diagnosis and then hierarchical clustering was performed within diagnosis group.

Figure 2:

Comparison of median relative abundance for Lactobacillus genus, L. crispatus/jensenii and L. iners between diagnosis groups. Using the Kruskall-Wallis test, no significant difference was demonstrated between groups.

Figure 3:

Comparison of median vaginal immunoglobulin concentration between diagnosis groups, demonstrating lower level of IgE in women with vulvodynia compared to healthy controls.

Figure 4:

Heatmap of log-transformed soluble immune marker values. No significant differences in values were seen between diagnosis groups.