A decrease in specific health-associated commensals is linked to progressive periodontal tissue destruction independent of dysbiotic community profiles

Abstract

Periodontitis is a chronic inflammatory disease associated with dysbiotic microbial communities that leads to destruction of the tooth-supporting tissues. The transition from host-microbial periodontal homeostasis to disease remains poorly understood. The murine ligature-induced periodontitis model was employed to characterize the temporal dynamics of the subgingival microbiome and host tissue features. Ligatures were placed in C57BL/6N mice, and collected on days 0, 1, 3, 5, and 7 post-induction. Bacterial load, alveolar bone loss, immune cells (CD45), cells with osteoclastogenic potential (TRAP) and collagen destruction were analyzed. Additionally, the V4 region of the 16S rRNA gene was sequenced for ecological analyses, including co-occurrence networks and functional prediction. Spatial distribution of the most abundant species was visualized using CLASI-FISH microscopy. Finally, association models were performed to link bacterial abundances with time and tissue parameters. The most substantial microbial shift occurred on day 1, and a dysbiotic community was established by day 3. CD45 cell infiltration increased as early as day 1, preceding the rise in TRAP cells on day 3 and the onset of tissue destruction on day 5. By day 7, predicted bacterial functions included protein export, lipid and galactose metabolism. Health-associated taxa were identified, and their abundance correlated positively with collagen integrity and negatively with immune cell infiltration and bacterial load, highlighting their role in homeostasis. These findings provide a high-resolution temporal map of microbiome-host interactions during experimental periodontitis establishment and identify specific microbial and cellular windows for potential therapeutic intervention.