A systems biology approach to evaluate potential probiotic candidates for women's vaginal health

Probiotic supplements are marketed for diverse health benefits, yet species inclusion often lacks functional rationale. We surveyed 352 U.S. probiotic products and found 36 unique microbial species, with most supplements containing only one species and no clear link between species and intended health benefit. To evaluate probiotic function, we developed CoPaPro, a collection of 1,012 genome-scale metabolic models spanning commensal, pathogenic, and probiotic bacteria. Flux balance analysis revealed that current probiotic species fail to capture the metabolic diversity of native commensals. Focusing on vaginal health, we identified commensals with metabolic profiles overlapping Gardnerella vaginalis , a key pathobiont. In vitro spent media assays using 11 vaginal isolates showed variable inhibition of G. vaginalis , primarily driven by D-lactic acid production rather than metabolic similarity. Several non- Lactobacillus species produced inhibitory levels of D-lactate. These findings highlight the need for function-based probiotic design and demonstrate a scalable framework integrating metabolic modeling with experimental validation.