Dental caries is closely associated with the microbial disequilibrium between acidogenic/aciduric pathogens and
alkali-generating commensal residents within the
dental plaque.
Fluoride is a widely used anticaries agent, which promotes tooth hard-tissue remineralization and suppresses bacterial activities. Recent clinical trials have shown that
oral hygiene products containing both
fluoride and
arginine possess a greater anticaries effect compared with those containing
fluoride alone, indicating synergy between
fluoride and
arginine in caries management. Here, we hypothesize that
arginine may augment the ecological benefit of
fluoride by enriching
alkali-generating bacteria in the plaque biofilm and thus synergizes with
fluoride in controlling
dental caries. Specifically, we assessed the combinatory effects of NaF/
arginine on planktonic and biofilm cultures of Streptococcus mutans, Streptococcus sanguinis, and Porphyromonas gingivalis with checkerboard microdilution assays. The optimal NaF/
arginine combinations were selected, and their combinatory effects on microbial composition were further examined in single-, dual-, and 3-species biofilm using bacterial species-specific fluorescence in situ hybridization and quantitative polymerase chain reaction. We found that
arginine synergized with
fluoride in suppressing acidogenic S. mutans in both planktonic and biofilm cultures. In addition, the NaF/
arginine combination synergistically reduced S. mutans but enriched S. sanguinis within the multispecies biofilms. More importantly, the optimal combination of NaF/
arginine maintained a "streptococcal pressure" against the potential growth of oral anaerobe P. gingivalis within the alkalized biofilm. Taken together, we conclude that the combinatory application of
fluoride and
arginine has a potential synergistic effect in maintaining a healthy oral microbial equilibrium and thus represents a promising ecological approach to caries management.