Engineered Probiotic Hydrogel Alleviates Vaginitis via Antimicrobial and Anti-inflammatory Pathways

Vulvovaginal candidiasis (VVC), primarily caused by <i>Candida albicans</i>, is a prevalent infection that presents significant clinical challenges. Current antifungal treatments have limitations, including a narrow antimicrobial spectrum and a lack of anti-inflammatory effects. To address these limitations, we genetically modified <i>Bacillus subtilis</i> to produce high-molecular-weight hyaluronic acid (HMHA) for sustained local delivery of antimicrobial peptides (AMP) and HMHA at the infection site. The engineered <i>Bacillus subtilis</i> (<i>B. sub</i>@HMHA) hydrogel exhibited both antifungal and vaginal microbiome-modulating activities. Specifically, AMP effectively inhibited the growth of fungi and bacteria, while HMHA modulated local inflammatory responses, improving the vaginal microenvironment. By targeting both the infection and chronic inflammation, this probiotic hydrogel may help reduce recurrence rates and promote tissue repair, offering a promising alternative therapy for VVC.