Bacterial vaginosis as a polymicrobial biofilm ecosystem: microbial interactions, host responses and therapeutic challenges

The vaginal mucosa is a hormonally responsive barrier ecosystem in which epithelial integrity, immune tone and microbial composition are interconnected. In eubiotic states, estrogen-supported, Lactobacillus-dominated communities help maintain low pH, reinforce epithelial barrier function and modulate mucosal immunity through lactic acid and antimicrobial metabolites. Disruption of this equilibrium can lead to bacterial vaginosis (BV), a polymicrobial dysbiosis characterized by depletion of lactobacilli and formation of structured biofilms adherent to the vaginal epithelium. Genomic, transcriptomic and metabolomic studies increasingly support the view that BV reflects a spatially organized, metabolically integrated biofilm network rather than simple bacterial overgrowth. Gardnerella species are considered key early colonizers, forming an epithelial scaffold that recruits secondary anaerobes. Interspecies cross-feeding, glycan degradation, amine production and density-dependent regulation contribute to biofilm maturation, antimicrobial tolerance and persistence. These biofilms degrade mucus and weaken epithelial integrity through cytolytic and enzymatic activities, triggering low-grade mucosal inflammation with limited neutrophilic infiltration, favoring recurrence and increasing susceptibility to sexually transmitted infections and adverse reproductive outcomes. This review examines the establishment and organization of BV-associated polymicrobial biofilms in bacterial vaginosis, key interspecies interactions and virulence mechanisms, experimental approaches used to study these communities and implications of biofilm persistence for recurrence and emerging therapeutic strategies.