Synbiotic-fluoride therapy as a next-generation non-invasive approach for early enamel lesions

To investigate the remineralization potential of a synbiotic-fluoride (SF) therapy combining l-arginine (Arg), sodium fluoride (NaF), and Lacticaseibacillus rhamnosus GG (LRGG) under a multi-species pH-cycling model.

Artificial enamel carious lesions were created on human enamel specimens and subjected to a 72-h pH-cycling protocol incorporating multi-species biofilm (Streptococcus mutans, Streptococcus sanguinis, and Streptococcus gordonii). Eight groups were assessed: control, 0.03%Arg, 0.22%NaF, LRGG, 0.22%NaF+0.03%Arg, 0.03%Arg+LRGG, 0.22%NaF+LRGG, and the SF therapy. Remineralization outcomes were quantified by mineral density (MD) and mineral gain (MG) assessments using micro-CT, SEM-EDX for Ca/P, change in surface nano-hardness (ΔSNH) and nanohardness recovery (SHR), and biochemical enamel calcium/phosphate content analysis.

Post pH-cycling, SF therapy had the highest MD, MG, and % remineralization (p < 0.001). The SF therapy also exhibited the significantly highest Ca/P ratio on SEM-EDX (p < 0.001), along with the highest SNH, ΔSNH, and SHR , indicating superior remineralization than other groups (p < 0.001). Calcium and phosphate content further confirmed the enhanced remineralization potential of SF therapy. While dualagent combinations demonstrated greater remineralization than monotherapies, none matched the synergistic effect observed with the SF therapy.

The combined application of Arg, F, and LRGG synergistically enhances enamel remineralization under dynamic biofilm-mediated conditions, outperforming both individual/combined treatment components.

Synbiotic-fluoride therapy represents a biofilm-mediated, noninvasive strategy for managing early enamel carious lesions, offering substantial advantages over fluoride alone. The therapy is aimed at high caries-risk individuals for primary and secondary caries prevention by promoting a biotic approach that ultimately aims to establish an eubiotic state.