Zinc‐stabilized stannous fluoride modulates the periodontal microbiome, reducing Fusobacteria, key Gram‐negative species, and overall inflammation within an experimental gingivitis clinical trial

BACKGROUND: This study aimed to evaluate the effects of a dentifrice containing stannous fluoride stabilized with zinc phosphate on subgingival microbiome composition and clinical inflammation during experimental gingivitis, compared with a sodium fluoride control. METHODS: This investigation was conducted as a secondary analysis of a randomized, parallel-arm, double-blind, controlled clinical trial. Clinical resolution of experimental gingivitis was assessed using bleeding on probing, gingival index, and plaque index. Deeply sequenced subgingival plaque metagenomic data were analyzed to compare microbial composition and functional potential between a stannous fluoride stabilized with zinc phosphate dentifrice (test) and a sodium fluoride dentifrice (control) over a 21-day experimental gingivitis period. RESULTS: Use of the stannous fluoride stabilized with zinc phosphate dentifrice was associated with depletion of periodontal disease-associated Gram-negative bacteria, including Fusobacterium nucleatum and multiple Porphyromonas and Prevotella species. This reduction in Gram-negative taxa corresponded with shifts in microbial community metabolic functions and was associated with significantly reduced clinical inflammation compared with the control over the 21-day period. CONCLUSIONS: Short-term use of stannous fluoride stabilized with zinc phosphate may provide additional protection against gingival inflammation by limiting the outgrowth of key periodontal pathogens, including the bridging organism Fusobacterium nucleatum, and by altering plaque functional capacity. These effects were associated with improved periodontal health outcomes compared with a standard sodium fluoride dentifrice. PLAIN LANGUAGE SUMMARY: In this study, we analyzed bacteria within the periodontal pocket using deep metagenomic sequencing to better resolve bacterial species and their functions. Results from this study show that using a toothpaste containing stannous fluoride stabilized with zinc phosphate was associated with the reduction of several important Gram-negative bacteria associated with periodontal disease, including Fusobacterium nucleatum and species of Porphyromonas and Prevotella compared with a control toothpaste. These bacteria are well‑known contributors to gingival inflammation and biofilm maturation. When levels of these specific bacteria decreased within the stannous fluoride treatment group, the overall subgingival microbiome shifted which notably persisted during the subsequent 21-day oral hygiene abstention period in this experimental gingivitis model - resulting in significantly lower clinical inflammation. Our findings suggest that even short‑term use of stannous fluoride stabilized with zinc phosphate may provide added protection against early gingival inflammation. Notably, stannous fluoride stabilized with zinc phosphate appears to limit the growth of key periodontal pathogens-particularly Fusobacterium nucleatum, an important bridging organism in subgingival biofilms-and may alter the functional activity of dental plaque in ways that support improved periodontal health when compared with a standard sodium fluoride toothpaste.