Highlight signatures of vaginal microbiota and metabolome contributed to the occurrence and recurrence of vulvovaginal candidiasis

ABSTRACT Vulvovaginal candidiasis (VVC) is a common vaginal infectious disease caused by Candida . The high recurrence rate of VVC is a great clinical challenge, with recurrent VVC (RVVC) defined as four or more episodes within a year. In this study, we recruited 31 RVVC patients, 28 VVC patients, and 29 healthy women. Vaginal samples were collected for metagenomic and metabolic analysis. RVVC and VVC groups presented similar clinical symptoms, with only a significantly increased incidence of swelling in the VVC group. Vaginal microbiota in VVC/RVVC exhibited a decreased abundance of Lactobacillus and increased bacterial vaginosis-associated bacteria, such as Gardnerella , Prevotella , and Atopobium . Notably, Lactobacillus iners was higher in RVVC, suggesting not all Lactobacillus species are protective. Healthy women showed lower overall microbiota diversity, emphasizing single-species dominance for stability. Glycogen metabolism pathways were enriched in RVVC/VVC, and were correlated with Atopobium vaginae , Prevotella bivia , and Lactobacillus jensenii . Peptidoglycan synthesis pathways, associated with P. bivia , were enriched, with the substrate L-glutamate elevated in RVVC, possibly promoted by L. iners . These findings shed light on potential therapeutic targets for recurrent VVC, contributing to the understanding of the intricate interplay between the metabolism of vaginal microbiome and disease. IMPORTANCE This study enhances our knowledge of the vaginal microbiota dynamics and the role of associated metabolites in individuals with vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis through shotgun sequencing and multi-omics analysis. The relationship between metabolites and vaginal microbiota and disease state was revealed. The accumulation of L-glutamate generated in glycogen metabolism, which is governed by Lactobacillus iners or bacterial vaginosis-associated bacteria, may contribute to the incidence and recurrence of VVC. Such insights have the potential to impact the treatment and prevention strategies for these common yet distressing conditions, potentially leading to targeted therapies and improved patient outcomes.