Purpose Recurrent Vulvovaginal Candidiasis (RVVC) is a problematic clinical condition for which fluconazole treatment is commonly prescribed. This study investigated the interkingdom vaginal and gastrointestinal microbiomes of RVVC patients who use fluconazole intermittently or as longer-term maintenance therapy for symptom management and compared them to healthy controls.

Methods Vaginal swabs and fecal samples were collected. A novel interkingdom analysis was performed using 16 S rRNA and ITS1 gene sequencing to compare the diversity and taxonomic composition of vaginal microbiome (VMB) and gastrointestinal microbiome (GIMB).

Results Twenty-seven women participated: 10 intermittent users and healthy controls and 7 maintenance therapy. The study revealed that microbiomes of fluconazole users do not differ in diversity metrics from healthy controls. RVVC patients using intermittent fluconazole displayed a higher abundance of vaginal C. albicans than healthy controls. Candida species pairings were not commonly observed between sites in individuals and, as such a fecal reservoir is unlikely to be implicated in recurrent symptomatology. In many of the RVVC non-Candida fungal spp. were identified in the vaginal microbiome. Users of fluconazole displayed elevations of the CST-I (Community State Type 1) associated bacterium L. crispatus. All participants displaying vaginal Candida spp. belonged to either bacterial CST-I or CST-III (Community State Type 3- L. iners associated).

Conclusion To our knowledge, this is the first study to compare the interkingdom VMB-GIMB of women with RVVC using oral fluconazole. As fluconazole users in this study represent a typical RVVC population, trends observed in microbial abundance require further analysis to establish fluconazole’s long-term microbiome safety. Examining the microbiome at both sites adds to the current understanding of microbial associated with the condition.