Food-grade Lacticaseibacillus paracasei postbiotics suppress oral Streptococcus mutans biofilm formation and cariogenicity.

Dental caries is a highly prevalent non-communicable disease driven by dysbiosis of the oral microbiota, in which Streptococcus (S.) mutans plays a keystone role. We discovered that cell-free supernatant (CFS) from food-associated Lacticaseibacillus (L.) paracasei disrupts S. mutans membranes, causing leakage, reduced viability, and decreased surface hydrophobicity. CFS also inhibits biofilms by decreasing biomass, metabolic activity, chain length, and exopolysaccharide (EPS) accumulation. Neutralization experiments revealed organic acids as the primary antibacterial factors: activity weakened at pH > 6 but remained stable after heating and long-term storage. In a hydroxyapatite disc model, CFS markedly suppressed biofilm formation and reduced free calcium release, indicating lower cariogenic potential. Transcriptomic analysis revealed downregulation of virulence and quorum-sensing genes (including stsR, gbpA, gbpB, scrB, ldh, aguB, atpA, atpD, luxS, ciaR, ciaH, and ciaX), while metabolomic studies identified creatine and phosphoenolpyruvate as key metabolites linked to these pathways. Our findings demonstrate that L. paracasei postbiotics can act as stable, food-compatible ingredients to modulate cariogenic biofilms, providing a mechanistic basis for developing next-generation postbiotic-based oral care and functional food products. This work connects the science of food-derived postbiotics with oral health, contributing to a One Health approach to caries prevention.