Lacticaseibacillus Paracasei Regulates Vaginal Microecology and Inhibits Hyphae Formation for Candida Vaginitis Therapy.

Vulvovaginal candidiasis (VVC) is a prevalent global health issue that significantly impairs the quality of life for millions of women. The rising incidence of azole resistance and high recurrence rates underscore the urgent need for alternative therapeutic strategies. This study investigates a novel probiotic approach targeting the key virulence trait of Candida albicans-the yeast-to-hyphal transition-using Lacticaseibacillus paracasei CPU-Lps0708, a strain isolated from healthy human vaginal secretions. The cell-free culture supernatant (CFCS) of L. paracasei CPU-Lps0708 exhibited potent anti-Candida activity, inhibiting hyphal formation by 40% and biofilm formation by approximately 35%. In a murine VVC model, the strain reduced the vaginal fungal burden by 114-fold. Our experiments revealed dual protective mechanisms: the strain enhanced host resistance in a Caenorhabditis elegans infection model and mitigated fungal burden, epithelial invasion, and inflammation in mice. Furthermore, L. paracasei CPU-Lps0708 modulated the vaginal microbiota, promoting beneficial Lactobacillus spp. while suppressing pathogenic Escherichia populations. These findings highlight the strain's multifaceted therapeutic potential, which combines direct antifungal activity with microbiota regulation and immune response modulation. L. paracasei CPU-Lps0708 thus represents a promising biotherapeutic candidate that addresses both pathogen virulence and host microenvironment restoration.