Diverse vaginal microbiomes in reproductive-age women with vulvovaginal candidiasis

Abstract

Vulvovaginal candidiasis (VVC) is one of the most prevalent vaginal infectious diseases, and there are controversial reports regarding the diversity of the associated vaginal microbiota. We determined the vaginal microbial community in patients with VVC, bacterial vaginosis (BV), and mixed infection of VVC and BV using Illumina sequencing of 16S rRNA tags. Our results revealed for the first time the highly variable patterns of the vaginal microbiome from VVC patients. In general, the alpha-diversity results of species richness and evenness showed the following order: normal control < VVC only < mixed BV and VVC infection < BV only. The beta-diversity comparison of community structures also showed an intermediate composition of VVC between the control and BV samples. A detailed comparison showed that, although the control and BV communities had typical patterns, the vaginal microbiota of VVC is complex. The mixed BV and VVC infection group showed a unique pattern, with a relatively higher abundance of Lactobacillus than the BV group and higher abundance of Prevotella, Gardnerella, and Atopobium than the normal control. In contrast, the VVC-only group could not be described by any single profile, ranging from a community structure similar to the normal control (predominated with Lactobacillus) to BV-like community structures (abundant with Gardnerella and Atopobium). Treatment of VVC resulted in inconsistent changes of the vaginal microbiota, with four BV/VVC samples recovering to a higher Lactobacillus level, whereas many VVC-only patients did not. These results will be useful for future studies on the role of vaginal microbiota in VVC and related infectious diseases.

Figure 1. Genus-level distribution of the vaginal microbiota determined in the present study.

(a) Relative abundance of NC, VVC, BV/VVC, and BV. (b–h) Percentage of specific genera in NC, VVC, BV/VVC, and BV. (b) Atopobium; (c) Dialister; (d) Gardnerella; (e) Lactobacillus; (f) Prevotella; (g) Sneathia.

Figure 2. Alpha- and beta-diversity comparison.

(a) Comparison of the Shannon index of NC, VVC, BV/VVC, and BV using a one-way ANOVA (p<0.05). (b) Pair-wise comparison of the Shannon index using Dunn's test. (c) PCoA analysis with weighted UniFrac distance. (d) Comparison of the weighted UniFrac distances of each group against NC. The statistical analysis was implemented using one-way ANOVA by ranks (normality test failed, p<0.05) and Dunn's test for pairwise comparisons (p<0.05 for all pair-wise comparisons).

Figure 3. Clustering of the samples using weighted UniFrac distances.

Each dot represents a sample, and each ring color represents a feature. A deeper ring color indicates that the value of that feature in that sample is larger.

Figure 4. Comparison of community structures before and after treatment.

Microbiomes from the same subject were grouped together. For each individual, the first two samples were those before treatment, and the last two were after treatment. Gray lines are used to separate different individuals, and black lines are used to separate different groups.