Limosilactobacillus fermentum 21 N1 Mitigates Candida albicans-Induced Vulvovaginal Candidiasis and Suppresses NLRP3 Inflammasome Activation in a Mouse Model

Vulvovaginal candidiasis (VVC), primarily caused by Candida albicans, is a common fungal infection that typically causes inflammation and discomfort. Current antifungal treatments, such as fluconazole, are associated with adverse effects and drug resistance, highlighting the need for alternative therapies. In this study, we investigated the antifungal efficacy of Limosilactobacillus fermentum 21N1 (LF21) against C. albicans using both in vitro assays and a murine model of VVC. A spotting assay assessed the inhibitory activity of LF21 against C. albicans. A murine VVC model was established by intravaginally inoculating C. albicans. Fungal burden, inflammation, and histopathological changes were assessed using colony counting, H&E, and PAS staining. Immunofluorescence and Western blot analyses quantified the expression of NLRP3 inflammasome and pyroptosis-related proteins. In vitro experiments using a spot formation assay revealed that LF21significantly inhibited C. albicans growth. Additionally, oral administration of LF21 alleviated VVC symptoms in mice inoculated with C. albicans, reducing the vaginal fungal burden and IL-1β levels. Histological analysis revealed reduced polymorphonuclear neutrophil infiltration and decreased C. albicans presence in the vaginal tissues of LF21-treated mice. LF21 treatment significantly reduced the expression of NLR family pyrin domain containing 3 (NLRP3) inflammasome components and pyroptosis-related proteins, including gasdermin-D, which were upregulated in response to the inoculation of C. albicans. These findings suggest that LF21 exerts antifungal effects by modulating the NLRP3 inflammasome and consequently reducing inflammation, indicating its potential as a novel therapeutic agent for treating VVC.