Systems-level restoration of vaginal and gut microbiota by Lactobacillus helveticus 20838 alleviates Gardnerella vaginalis-induced dysbiosis.

Bacterial vaginosis (BV), often driven by Gardnerella vaginalis overgrowth, is characterized by epithelial disruption, inflammation, and microbiome dysbiosis across the vaginal and gut ecosystems. Affecting a majority of women during their reproductive years, BV increases the risk of infection and reproductive complications. Here, we identify a novel probiotic strain, Lactobacillus helveticus 20838, exhibiting potent antagonistic activity against G. vaginalis and evaluate its ecological and immunological effects in a murine model of vaginitis. Comparative genomics revealed distinct adaptive and antimicrobial traits of L. helveticus 20838 relatives to the reference strain DPC4571. Both oral and intravaginal administration reduced G. vaginalis colonization, suppressed Tnf-α and Il-1β expression in vaginal tissue, and prevented pathological epithelial thickening. Multi-omics profiling of fecal and vaginal samples demonstrated restoration of microbial alpha and beta diversity disrupted by infection. The L. helveticus 20838 reduced dysbiosis-associated taxa such as Staphylococcaceae, whereas enriching protective Lactobacillus species, with intravaginal delivery achieving superior local recolonization of Lactobacillaceae. Collectively, these findings identify L. helveticus 20838 as a next-generation probiotic that alleviates G. vaginalis-induced dysbiosis by restoring microbial and immune homeostasis across interconnected mucosal niches, providing a systems-level framework for microbiota-targeted therapy in women's health.