The mouse experimental periodontitis by silk-ligature placement triggers systemic inflammation potentially exacerbating pulmonary inflammation.

Abstract

Periodontitis, a chronic inflammatory disease driven by oral microbiota dysbiosis, is associated with systemic diseases; however, the mechanisms remain poorly understood. Using a silk-ligation-induced periodontitis mouse model, we investigated the changes in oral microbiota, immune responses, and systemic effects, including respiratory disease. Oral dysbiosis persisted for five weeks and was characterized by an increased abundance of genera Enterococcus, Proteus, and Escherichia_Shigella, and a decrease in genera Lactococcus. Antibiotic treatment effectively reduced alveolar bone resorption and suppressed both oral and systemic inflammation, suggesting that the dysbiosis induced innate immune activation in the gingiva which led to alveolar bone resorption and systemic immune activation. Notably, while gingival inflammation and bone resorption subsided within 2-3 weeks, systemic immune activation persisted throughout the experimental period with elevated levels of Th17 cytokines, particularly IL-17A and IL-22. To further examine the systemic impact, we induced pulmonary fibrosis with bleomycin after the onset of periodontitis. Periodontitis exacerbated initial lung inflammation, marked by increased production of IL-17A, IL-22, and IL-1β, along with significant T-cell infiltration in lung tissue. These findings reveal a chronic systemic inflammation induced by periodontitis and highlight its potential role in exacerbating respiratory diseases.