Combinatorial Effects of Arginine and Fluoride on Oral Bacteria

Abstract

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.

Demineralization–remineralization dynamics in teeth and bone

“…The arginine is broken down into ammonia by nonpathogenic arginolytic bacteria; ammonia helps in neutralizing plaque acid and maintaining the plaque biofilm on tooth surface in a healthy state. 63,135,136 Diet control and oral hygiene instructions Additionally, dietary advice, oral hygiene instruction, and application of fissure sealants are still used as further preventive regime to dental caries in both high-and low-risk individuals. In most recent studies, it was shown that the use of nonfermentable sugars in chewing gum, such as xylitol, was seen to inhibit the effect of S. mutans; however, more conclusive evidence is yet to be achieved.…”

Ecological Approaches to Dental Caries Prevention: Paradigm Shift or Shibboleth?

“…Among such biofilm-modifying oral products, there is now sufficient evidence supporting fluoride-arginine combinations as a new standard of care for caries prevention [ten Cate and Cummins, 2013;Zheng et al, 2015]. Likewise, a dentifrice containing enzymes and proteins was shown to significantly shift the ecology of the oral microbiome resulting in a community with a stronger association to health [Adams et al, 2017].…”

“…In vitro biofilm experiments found that fluoride-arginine combinations synergistically inhibited S. mutans but enriched S. sanguinis growth within multispecies biofilms, while maintaining a "streptococcal pressure" against the potential growth of oral anaerobe Porphyromonas gingivalis in the alkalized biofilm [Zheng et al, 2015]. Fluoride-arginine combinations can also suppress exopolysaccharide production, thus targeting another critical virulence factor for cariogenic biofilms [Zheng et al, 2015].…”

“…In vitro biofilm experiments found that fluoride-arginine combinations synergistically inhibited S. mutans but enriched S. sanguinis growth within multispecies biofilms, while maintaining a "streptococcal pressure" against the potential growth of oral anaerobe Porphyromonas gingivalis in the alkalized biofilm [Zheng et al, 2015]. Fluoride-arginine combinations can also suppress exopolysaccharide production, thus targeting another critical virulence factor for cariogenic biofilms [Zheng et al, 2015]. Human in situ studies and several double-blinded RCTs using a fluoride dentifrice containing 1.5% arginine and an insoluble calcium compound have shown significantly greater protection against carious lesions than a fluoride dentifrice alone [Cantore et al, 2013;Kraivaphan et al, 2013;Srisilapanan et al, 2013;Yin et al, 2013;Petersen et al, 2015].…”

Understanding Dental Caries

“…In vitro results showed that the combinatory application of fl uoride and arginine has a potential synergistic effect in maintaining a healthy oral microbial equilibrium and thus represents a promising ecological approach to caries management (Zheng et al 2015 ). In vitro results showed that the combinatory application of fl uoride and arginine has a potential synergistic effect in maintaining a healthy oral microbial equilibrium and thus represents a promising ecological approach to caries management (Zheng et al 2015 ).…”