Limosilactobacillus fermentum 50 Alleviates Vulvovaginal Candidiasis via the Gut-Vagina Axis: Modulating Microbiota, Barrier Function and Inflammation

Abstract

Vulvovaginal candidiasis (VVC) is a common vaginal disease characterized by inflammatory cell infiltration and vaginal microbiota dysbiosis. In this study, Limosilactobacillus fermentum 50 not only exhibited the strongest growth-inhibitory activity against Candida albicans using a spot assay, but also significantly suppressed hyphal formation and decreased the expression of virulence-associated genes, including HWP1, ALS3, and ECE1. Furthermore, the effects of L. fermentum 50 on C. albicansinduced VVC were investigated in a mice model. Oral administration L. fermentum 50 increased body weight, reduced vaginal epithelial cell exfoliation , and decreased fungal burden. RT-qPCR analysis revealed that L. fermentum 50 significantly downregulated expression of S100A8, S100A9 and TNF-α, and upregulated IL-10 expression at the transcription level in vaginal tissue. ELISA analysis further confirmed that L. fermentum 50 increased the level of IL-10 and decreased the level of TNF-α in both vaginal tissue and serum. Histopathological analysis showed that L. fermentum 50 significantly reduced epithelial cell exfoliation and alleviated vaginal structural damage by increasing the expression of Occludin. In addition, L. fermentum 50 modulated the composition of the vaginal microbiota, characterized by an increased abundance of Lactobacillus and a decreased abundance of Escherichia coli. It is noteworthy that L. fermentum 50 also reshaped composition of the gut microbiota, also enriching the abundance of Lactobacillus. Correlation analyses further revealed that Lactobacillus abundance in fecal was positively associated with vaginal Lactobacillus and negative correlation with vaginal Escherichia-Shigella abundance. Collectively, these findings suggested that L. fermentum 50 may serve as a potential strategy to ameliorate VVC by modulating the gut microbiota to alleviate vaginal inflammation, enhancing mucosal barrier function, and restoring vaginal microbiota composition.