Hyperuricemia is associated with periodontal ligature dysbiosis in a murine model of experimental periodontitis.

BACKGROUND: Hyperuricemia (Hu) is a systemic metabolic disorder implicated in inflammatory conditions and has been epidemiologically associated with an increased prevalence of periodontitis. However, whether Hu is associated with periodontal microbial dysbiosis in experimental periodontitis remains unclear. OBJECTIVE: This exploratory pilot study aimed to investigate whether Hu is associated with periodontal dysbiosis in experimental periodontitis by characterizing the diversity, taxonomic composition, and predicted functional potential of ligature-associated microbiota using 16S rRNA sequencing. METHODS: A mouse model combining potassium oxonate-induced Hu with ligature-induced periodontitis was established. Male C57BL/6 mice were allocated to normouricemia with periodontitis (NuP), hyperuricemia with periodontitis (HuP), and allopurinol-treated hyperuricemia with periodontitis (HuP+Allo) groups. Ligature-associated microbiota were analyzed by 16S rRNA gene sequencing. Correlations between microbial alterations and biochemical parameters were evaluated using redundancy analysis. RESULTS: Hu significantly increased microbial diversity and evenness, as indicated by higher Shannon index (P = 0.007) and Shannoneven index (P = 0.002), but did not affect community richness. At the phylum level, Hu increased the Firmicutes/Bacteroidota ratio and Proteobacteria abundance while decreasing Bacteroidota and Actinobacteriota. At the genus level, Hu enriched potentially pathogenic taxa, including Streptococcus and Escherichia-Shigella. Allopurinol partially reversed these changes. Redundancy analysis revealed that microbial shifts were significantly correlated with serum uric acid (R2  = 0.711, P = 0.040) and creatinine (R2  = 0.695, P = 0.035). Functional prediction suggested that Hu was associated with higher predicted abundances of NOD-like receptor signalling and lower predicted abundance of IL-17 signalling pathways. CONCLUSION: These exploratory findings suggest that Hu may be associated with dysbiotic remodeling of the periodontal ligature microbiota in experimental periodontitis, linking systemic metabolic disturbance with local microbial imbalance and inflammatory pathway alteration. These alterations were partially reversed by allopurinol and correlated with serum uric acid and creatinine, providing mechanistic insight into how Hu may aggravate periodontal tissue destruction.