Targeting vaginal dysbiosis: Lactobacillus helveticus 20838 restores microbiota composition and epithelial integrity

Bacterial vaginosis (BV), frequently associated with G. vaginalis overgrowth, is characterized by epithelial disruption, inflammation, and microbiome dysbiosis across the vaginal and gut niches. Affecting more than 70% of women during their reproductive years, BV increases the risk of adverse reproductive outcomes and secondary infections. We identified a novel L. helveticus 20838 strain, with potent antagonistic activity against G. vaginalis and evaluated its therapeutic efficacy in a murine model of vaginitis. Comparative genomics revealed distinct features of L. helveticus 20838 compared with the reference strain DPC4571. Both oral and intravaginal delivery significantly reduced G. vaginalis burden, suppressed Tnf-α and Il-1β expression in vaginal tissue, and prevented pathological epithelial thickening. Multi-omics analysis of fecal and vaginal samples demonstrated restoration of alpha and beta diversity disrupted by infection. Notably, L. helveticus 20838 corrected taxonomic imbalances by reducing dysbiosis-associated taxa such as Staphylococcaceae while enriching protective commensals, particularly Lactobacillus spp. Intravaginal administration resulted in greater local enrichment of Lactobacillaceae, highlighting the importance of delivery route for site-specific efficacy. Collectively, these results establish L. helveticus 20838 as a next-generation probiotic capable of suppressing BV-associated pathogens, mitigating inflammation, and re-establishing microbiota homeostasis, supporting its potential as a microbiome-targeted therapy for vaginal health.