National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangdong Key Laboratory of Vascular Disease, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Department of Intensive Care Unit, School of Medicine, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China.
Br J Pharmacol. 2023 Aug;180(16):2102-2119. doi: 10.1111/bph.16064. Epub 2023 Apr 9.
The causal relationship between altered host microbiome composition, especially the respiratory tract microbiome, and the occurrence of pulmonary hypertension (PH) has not yet been studied. An increased abundance of airway streptococci is seen in patients with PH compared with healthy individuals. This study aimed to determine the causal link between elevated airway exposure to Streptococcus and PH.
The dose-, time- and bacterium-specific effects of Streptococcus salivarius (S. salivarius), a selective streptococci, on PH pathogenesis were investigated in a rat model established by intratracheal instillation.
Exposure to S. salivarius successfully induced typical PH characteristics, such as elevated right ventricular systolic pressure (RVSP), right ventricular hypertrophy (Fulton's index) and pulmonary vascular remodelling, in a dose- and time-dependent manner. Moreover, the S. salivarius-induced characteristics were absent in either the inactivated S. salivarius (inactivated bacteria control) treatment group or the Bacillus subtilis (active bacteria control) treatment group. Notably, S. salivarius-induced PH is characterized by elevated inflammatory infiltration in the lungs, in a pattern different from the classic hypoxia-induced PH model. Moreover, in comparison with the SU5416/hypoxia-induced PH model (SuHx-PH), S. salivarius-induced PH causes similar histological changes (pulmonary vascular remodelling) but less severe haemodynamic changes (RVSP, Fulton's index). S. salivarius-induced PH is also associated with altered gut microbiome composition, suggesting potential communication of the lung-gut axis.
This study provides the first evidence that the delivery of S. salivarius in the respiratory tract could cause experimental PH in rats.
宿主微生物组组成的改变，尤其是呼吸道微生物组，与肺动脉高压（PH）的发生之间的因果关系尚未得到研究。与健康个体相比，PH 患者的气道链球菌丰度增加。本研究旨在确定气道暴露于链球菌与 PH 之间的因果关系。
通过气管内滴注建立大鼠模型，研究了唾液链球菌（S. salivarius），一种选择性链球菌，对 PH 发病机制的剂量、时间和细菌特异性影响。
S. salivarius 暴露成功地以剂量和时间依赖的方式诱导出典型的 PH 特征，如右心室收缩压（RVSP）升高、右心室肥厚（富尔顿指数）和肺血管重塑。此外，在灭活 S. salivarius（灭活细菌对照）治疗组或枯草芽孢杆菌（活性细菌对照）治疗组中，均未观察到 S. salivarius 诱导的特征。值得注意的是，S. salivarius 诱导的 PH 以肺部炎症浸润增加为特征，与经典缺氧诱导的 PH 模型不同。此外，与 SU5416/缺氧诱导的 PH 模型（SuHx-PH）相比，S. salivarius 诱导的 PH 引起相似的组织学变化（肺血管重塑）但血流动力学变化较轻（RVSP、富尔顿指数）。S. salivarius 诱导的 PH 也与肠道微生物组组成的改变有关，提示肺-肠轴之间存在潜在的通讯。
本研究首次提供了证据，表明呼吸道中 S. salivarius 的输送可导致大鼠实验性 PH。
