Correlation Analysis of Vaginal Microbiome Changes and Bacterial Vaginosis Plus Vulvovaginal Candidiasis Mixed Vaginitis Prognosis

Abstract

Mixed vaginitis is the result of the simultaneous presence of different pathogenic processes mediated by at least two types of vaginal pathogens. Among the various types of mixed vaginitis presentations, bacterial vaginosis (BV) plus vulvovaginal candidiasis (VVC) presents to be the most prevalent form. Mixed vaginitis affects the health of women of all ages worldwide. However, few studies have focused on clinical manifestations, pathogenesis, diagnostic criteria, or therapy of mixed vaginitis. We recruited 48 symptomatic patients with clinical diagnoses of VVC complicated with BV, they were treated with oral metronidazole combined with local clotrimazole and followed to assess the drug efficacy and vaginal microbiome alterations before and after treatment. The vaginal microbiome in BV+VVC mixed vaginitis patients was altered significantly after the combined drug treatment within a unique form different from a simple overlay mode of BV and VVC, the key bacteria including Gardnerella and Atopobium, Lactobacillus. The combined drug therapy for the mixed vaginitis in this study was effective and enhanced treatment for BV may be more favorable because of more difficulty in dealing with BV according to the treatment outcome. The abundance of Lactobacillus in patients with mixed vaginitis affects the recovery of the vaginal microbiome as well as the prognosis, and the abundance should be actively restored. This is the first study to investigate the composition, diversity, and other characteristics of the vaginal microbiome in patients with BV+VVC mixed vaginitis before and after drug treatment, our results provide clues to improving the cure rate and reducing recurrences.

Keywords: Atopobium; Gardnerella; Lactobacillus; bacterial vaginosis (BV); mixed vaginitis; vaginal microbiome; vulvovaginal candidiasis (VVC).

Figure 1

Microbiome of vaginal bacterial community. (A) Microbiome distribution obtained by PCoA clustering of the vaginal microbiota of all subjects; (B) heat maps of vaginal microbiome abundance distribution and the distribution of microbial community obtained by hierarchical clustering. (C) Shannon diversity index distribution in different microbial groups.

Figure 2

Changes in bacterial vaginal compositions in different patient groups. (A) Microbiota distributions before and after drug treatment. (B) Genus abundances before and after drug treatment. (C) Vaginal microbiome Shannon diversity indexes before and after drug treatment.

Figure 3

Key vaginal microorganism changes before and after treatment. LDA and T-test identified the most differentially abundant taxons between (A) patients completely cured (M1.1, M1.2) and patients with cured VVC plus uncured BV (M2.1, M2.2), (B) patients completely cured(M1.1, M1.2) and patients with cured BV plus uncured VVC (M3.1, M3.2), (C) patients completely cured (M1.1, M1.2) and patients with recurrence (MR.1, MR.2, MR.3).

Figure 4

Correlation between metabolites and key vaginal microbiota associated with the drug therapy outcomes. (A) Association of key vaginal microorganisms and metabolites in patients completely cured (M1.1, M1.2) and in patients with cured VVC and untreated BV (M2.1, M2.2). (B) Associations between key vaginal microorganisms and metabolites in completely cured patients (M1.1, M1.2) and in uncured patients (M3.1, M3.2). (C) Association of key vaginal microorganisms and metabolites in completely cured patients (M1.1, M1.2) and in patients with recurrence (MR.1, MR.2, MR.3). P value of Spearman’s correlation: ⁺<0.05, *<0.01.