Targeted elimination of Fusobacterium nucleatum alleviates periodontitis.

ABSTRACT

Background: Fusobacterium nucleatum, a pathobiont in periodontal disease, contributes to alveolar bone destruction. We assessed the efficacy of a new targeted antimicrobial, FP-100, in eradicating F. nucleatum from the oral microbial community in vitro and in vivo and evaluated its effectiveness in reducing bone loss in a mouse periodontitis model. Methods: A multispecies bacterial community was cultured and treated with two concentrations of FP-100 over two days. Microbial profiles were examined at 24-h intervals using 16S rRNA sequencing. A ligature-induced periodontitis mouse model was employed to test FP-100 in vivo. Results: FP-100 significantly reduced Fusobacterium spp. within the in vitro community (p < 0.05) without altering microbial diversity at a 2 µM concentration. In mice, cultivable F. nucleatum was undetectable in FP-100-treated ligatures but persistent in controls. Beta diversity plots showed distinct microbial structures between treated and control mice. Alveolar bone loss was significantly reduced in the FP-100 group (p = 0.018), with concurrent decreases in gingival IL-1ß and TNF-α expression (p = 0.052 and 0.018, respectively). Conclusion: FP-100 effectively eliminates F. nucleatum from oral microbiota and significantly reduces bone loss in a mouse periodontitis model, demonstrating its potential as a targeted therapeutic agent for periodontal disease.

FP-100 eliminates F. nucleatum from an in vitro multispecies microbial community at low doses without affecting bacterial diversity. FP-100 treatment leads to the in vivo elimination of F. nucleatum, reducing alveolar bone loss and levels of pro-inflammatory cytokines in the gingiva. FP-100 is a new antimicrobial to target F. nucleatum-mediated periodontal disease.