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该病的预防和治疗至关重要。在目前的研究中，我们发现实验性牙周炎（通过结扎磨牙，然后口腔涂抹牙周炎患者的龈下菌斑而建立）会加剧小鼠缺氧引起的肺动脉高压。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，导致肺部微生物群失调，导致干扰素γ阳性（IFNγ ⁺）T细胞肺部浸润，加剧肺动脉高压的进展。此外，我们还确定了动物普雷沃氏菌是导致牙周炎引起的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和IFNγ中和抗体均能有效缓解这种恶化。我们的研究证明了牙周炎和肺动脉高压的联合预防和治疗是必要的。