Septic arthritis drives alveolar bone loss in mice through microbiota-dependent functional shifts

Periodontal alterations, including alveolar bone loss (ABL), can be influenced by systemic inflammatory conditions and by changes in oral microbiota. Although periodontal disease (PD) provides an established framework for understanding how dysbiosis-driven inflammation affects the periodontium, the present study did not employ a PD model. Instead, we investigated whether septic arthritis (SA), an infectious arthritis, can modulate periodontal parameters. Specifically, we evaluated changes in the oral microbiota and the contribution of the CCR2 in SA-induced periodontal alterations.

SA was induced by injecting 10⁷ CFU/10 μL of Staphylococcus aureus into the joint cavity of the C57BL6/J or CCR2 knockout (Ccr2^-/-) mice. After seven days, maxillary tissues were analyzed for ABL and oral microbiota composition using 16S rRNA sequencing and functional prediction. Infected mice presented significant ABL and increased production of IFN-γ, as well as an increased RANKL/OPG ratio in periodontal tissues. The absence of CCR2, or local receptor antagonism with RS504393, reduced SA-induced ABL. Conversely, depletion of the oral microbiota by topical chlorhexidine inhibited ABL. Evaluation of the oral microbiota reveals no significant differences in overall alpha- or beta-diversity between groups, but subtle compositional shifts, particularly involving Rodentibacter and Muribaculaceae, were observed. In addition, SA-infected mice showed upregulation of bacterial metabolic pathways, including glucose and glucose-1-phosphate degradation.

Our study provides evidence that SA caused by S. aureus infection is associated with changes in ABL, functional shifts, and modest compositional changes rather than major community structural disruption.