Lactobacillus salivarius HHuMin-U attenuates vulvovaginal candidiasis via vaginal epithelial immune enhancement mediated by NF-κB activation

Vulvovaginal candidiasis (VVC), primarily caused by Candida albicans infection, is one of the most common diseases among women and leads to various symptoms that adversely impact quality of life. VVC is conventionally treated with antifungal agents, but the high recurrence rates and the risk of inducing vaginal microbiome dysbiosis pose major concerns in effective treatment. Probiotics with immune-enhancing properties can be an effective strategy by strengthening mucosal immunity and reducing susceptibility to infection. Herein, this study investigates the therapeutic potential of Lactobacillus salivarius HHuMin-U (HMU) as a probiotic agent for treating VVC. Phenotype screening identified HMU as a top candidate with antifungal activity against C. albicans. HMU significantly upregulated immunomodulatory factors such as antimicrobial peptides, cytokines, and chemokines in human vaginal epithelial cells, which can strengthen the antifungal immune system. In an animal study, administration of HMU in a mouse VVC model significantly decreased the fungal burden and protected the mice from vaginal infection. Additionally, cellular infection models revealed that HMU reduced fungal adhesion and the cytolytic activity of C. albicans, while conditioned media from HMU-treated epithelial cells inhibited fungal growth. Transcriptomic analysis revealed that HMU treatment enriched gene sets related to epithelial barrier integrity, innate immune responses mediated by epithelial cells, and immune cell regulation. Mechanistically, the NF-κB pathway emerged as a key mediator of these responses. Collectively, HMU inhibits VVC by enhancing epithelial immunity and thus could be considered as a probiotic agent for the prevention and treatment of VVC.