Women’s health is a team effort: probiogenomics supports the development of a multi-species vaginal probiotic

The healthy vaginal microbiota is typically dominated by Lactobacillus species, while the dominance of different taxa often signals dysbiosis. Vaginal probiotics offer a promising therapeutic avenue to restore microbial balance and prevent recurrent infections. Using probiogenomics, this study investigated 19 novel strains belonging to four Lactobacillus species (Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus paragasseri, Limosilactobacillus fermentum) isolated from the vaginal environment of fertile and menopausal women. Through genomic screening and comparative genomics, we identified complementary roles between these species in activities crucial to women’s health. Our results indicate that vaginal Lactobacillus strains are genomically adapted to this niche, promoting persistence and pathogen-fighting. Furthermore, we demonstrated the potential ability of vaginal lactobacilli to survive the gastrointestinal transit and to explicate beneficial activities at the intestinal level, suggestion the possibility to be used through oral supplementation when topical application is not feasible. Although we confirmed L. crispatus as the most specialized to the vaginal niche, L. gasseri showed equivalent and complementary genetic traits, highlighting its previously underestimated role. L. paragasseri showed an interesting dichotomy, with beneficial traits alongside potentially unfavorable ones, while Lm. fermentum of vaginal origin may potentially have a role in the gut-vagina axis. In conclusion, our results strongly support the development of multispecies and multistrain probiotic blends, as the combined metabolic cooperation of vaginal lactobacilli may offer greater efficacy for vaginal health compared to single-strain supplements.