Addition of cariogenic pathogens to complex oral microbiota drives significant changes in biofilm compositions and functionality

Dental caries is a microbe-mediated, fermentable carbohydrate-driven disease characterized by highly organized polymicrobial biofilm on tooth surfaces. A unique clinical feature of early childhood caries (ECC) is the synergistic interaction between the cariogenic bacterial pathogen, Streptococcus mutans, and an opportunistic fungal pathogen, Candida albicans. Although clinical cross-sectional studies have revealed that C. albicans is associated with a highly acidogenic and acid-tolerant bacterial community in severe ECC, it remains unclear the mechanism(s) through which the cross-kingdom interaction modulates the composition of the plaque microbiome. Furthermore, cross-sectional studies have limitations regarding the determination of the significance of microbial interactions between specific organisms in the pathogenesis of the disease. Here, we developed a novel in vitro saliva-derived microcosm biofilm system to assess the structural and functional characteristics of the saliva community by introducing exogenous pathogens and the influence of dietary sugars on the functionality of the oral microbiome. We applied shotgun whole metagenome sequencing and observed that the presence of C. albicans and S. mutans, alone or in combination, as well as the addition of different sugars induced unique alterations in both the composition and functional attributes of the biofilms. Our work provides a novel biofilm model for investigating the functional microbiome in health and disease as well as developing strategies to modulate the microbiome.