Decoding multispecies oral biofilms: molecular architecture, host modulation and systems-guided precision anti-biofilm strategies

Oral biofilms are spatially ordered microbial communities whose pathogenic behavior is shaped by more than taxonomic composition. Their development reflects the combined effects of adhesin-receptor recognition, interspecies coaggregation, matrix formation, metabolite exchange, local physicochemical gradients and host-derived selection. Here, we synthesize molecular and ecological evidence on the bacterial cell surface-matrix interface and consider how these interactions contribute to cariogenic, periodontal and peri-implant biofilms. Particular attention is given to glucosyltransferase-dependent polysaccharides, extracellular DNA, amyloidogenic proteins, sortase-anchored surface factors and outer membrane vesicles, together with metabolic interactions involving lactate, arginine, hydrogen peroxide and heme. We further evaluate functional-genomic and systems-level approaches (including transposon sequencing, CRISPR interference, metagenomics, metatranscriptomics, metaproteomics, metabolomics, spatial imaging, genome-scale metabolic modeling and machine learning) while distinguishing association and prediction from experimentally demonstrated mechanism. Emerging interventions are assessed according to their biological target and evidence level, including adhesion blockade, specifically targeted antimicrobials, matrix synthesis inhibition and degradation, quorum interference, probiotics, catalytic nanoparticles, antimicrobial photodynamic therapy and antibiofilm dental materials. Across these approaches, reduction in biofilm biomass is not equivalent to ecological restoration or clinical benefit. Key translational barriers include model fidelity, donor-to-donor variation, spatial heterogeneity, treatment durability, endpoint selection and the limited external validation of many computational and preclinical findings. Future precision strategies should therefore integrate microbial identity, matrix architecture, spatial metabolism and host context, with experimental perturbation used to establish causal vulnerabilities before therapeutic translation.