Cyclodextran prevents Porphyromonas gulae and Porphyromonas gingivalis induced halitosis and cytokine secretion via direct inhibition of biofilm formation

Periodontal disease (PD) is an inflammatory condition affecting the supporting structures of teeth, initiated by bacterial biofilm formation. <i>Porphyromonas gulae</i> (<i>P. gulae</i>) and <i>P. gingivalis</i> are key pathogens in canine and human PD, respectively, producing biofilms, volatile sulfur compounds, and proinflammatory cytokines that contribute to halitosis and tissue destruction. Cyclodextran (CI), a cyclic oligosaccharide, has previously been shown to inhibit glucan synthesis in Streptococcus mutans, but its effects on periodontal bacteria remain unexplored. This study investigated the influence of CI on <i>P. gulae</i> and <i>P. gingivalis in vitro</i>. Bacterial cultures were co-incubated with varying concentrations of a CI-dextran mix (0.313%-5%) for up to 24 h. Biofilm formation and insoluble glucan production were assessed via fluorescence microscopy and biochemical assays. Hydrogen sulfide and methyl mercaptan levels were measured by gas chromatography, and cytokine production (IL-1β, IL-6) was quantified in murine and canine macrophage cell lines using ELISA. CI had limited bactericidal activity but significantly inhibited biofilm formation and glucan production in both bacterial species. Consequently, hydrogen sulfide and methyl mercaptan generation were markedly reduced, although CI did not directly neutralize these compounds. Furthermore, CI treatment significantly suppressed <i>P. gulae</i> and <i>P. gingivalis</i>-induced IL-1β and IL-6 secretion in macrophages in a dose-dependent manner without cytotoxicity. These findings demonstrate that cyclodextran prevents PD-related halitosis and inflammation primarily by inhibiting biofilm formation rather than bacterial killing or direct deodorization. CI represents a promising candidate for preventive oral care in humans and companion animals, with potential to reduce the onset and progression of PD.