Saccharomyces cerevisiae reduces vulvovaginal candidiasis severity through modulation of fungal pathogenicity and inflammatory responses.

Vulvovaginal candidiasis (VVC) affects millions of women globally and is characterized by multifactorial immunopathology, with Candida albicans virulence driving disease progression through epithelial tissue damage and neutrophil hyperactivation and dysfunction contributing to disease severity. Here, we explored the multifaceted nature of S. cerevisiae as a live-biotherapeutic to attenuate C. albicans virulence and modulate host immune responses during VVC. We identified an S. cerevisiae isolate (Sc3458) that targets multiple aspects of C. albicans virulence, including fungal proliferation, adhesion, and hyphal morphogenesis, collectively impairing biofilm formation and disrupting pathogenic potential. These effects were linked to transcriptional reprogramming in C. albicans, marked by metabolic stress and downregulation of virulence- and biofilm-related genes. Additionally, S. cerevisiae (Sc3458) reduced inflammatory responses and neutrophil hyperactivation, while preserving neutrophil antimicrobial functionality. Altogether, this translated to an improved control of infection and dampened VVC-associated hyperinflammation in a murine VVC model. These findings position S. cerevisiae strain Sc3458 as a promising candidate live biotherapeutic for VVC treatment. Further clinical validation in human cohorts is essential to confirm its therapeutic efficacy and to assess how Sc3458 performs relative to established market-standard formulations.