Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease. In the current study, we showed that experimental periodontitis, which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis, exacerbated hypoxia-induced pulmonary hypertension in mice. Mechanistically, periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs, contributing to pulmonary infiltration of interferon gamma positive (IFNγ⁺) T cells and aggravating the progression of pulmonary hypertension. In addition, we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis, and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies. Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.

揭示肺动脉高压的危险因素及其机制对于预防和治疗该疾病至关重要。在目前的研究中，我们表明，通过结扎牙牙然后口服涂抹牙周炎患者龈下斑块而建立的实验性牙周炎加剧了缺氧诱导的小鼠肺动脉高压。从机制上讲，牙周炎通过促进肺部口腔细菌的异位定植和富集来失调肺微生物群，导致干扰素 γ 阳性 （IFNγ⁺） T 细胞的肺部浸润并加重肺动脉高压的进展。此外，我们确定 Prevotella zoogleoformans 是导致牙周炎导致肺动脉高压恶化的关键牙周炎相关细菌，并且颈部淋巴结切除术和 IFNγ 中和抗体均有效改善了恶化。我们的研究表明，牙周炎和肺动脉高压的联合预防和治疗是必要的概念证明。