Dual probiotic and antibiotic therapy targeting bacterial vaginosis: An integrated experimental/computational modeling perspective

Abstract

A novel strategy delivering both metronidazole and L. crispatus via 3D-printed scaffolds was recently shown to target pathogens in bacterial vaginosis (BV) while promoting beneficial microflora with sustained probiotic release, with the objective to facilitate user treatment adherence. This study developed an integrated experimental/computational platform to evaluate dual therapeutic strategy efficacy over a wide range of system dynamics, towards the goal of personalized therapy design. Experiments evaluated Gardnerella and L. crispatus interactions under controlled glucose concentrations in vitro, including bacterial growth, glucose consumption, lactic acid production, and pH. These data informed parameters of a novel computational model simulating the vagina, incorporating nutrient dynamics, bacterial interactions, and dual release of antibiotics and probiotics from 3D-printed scaffolds. Efficacy of varying concentrations of antibiotics and probiotics was assessed via sensitivity analyses. Experimental results demonstrate that L. crispatus outcompetes Gardnerella at lower glucose concentrations, while Gardnerella dominates at higher glucose levels. The computational model replicated these dynamics and projected that dual therapy could significantly suppress Gardnerella while promoting L. crispatus, even at lower drug dosages and probiotic CFU counts. Results were validated against data from 3D-printed dual release scaffolds. Simulated dual treatment enhanced lactic acid production and decreased vaginal pH, creating an unfavorable environment for pathogenic bacteria and shifting the microbiome composition towards the beneficial microflora. We conclude that an integrated experimental/computational modeling approach enables detailed evaluation of pathogenic and host bacteria interactions in the vaginal microbiome. This approach could advance personalized treatment for BV that eradicates pathogens while simultaneously restoring beneficial microflora.