State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China; Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Section of Physiology, Division of Pulmonary, Critical Care and Sleep Medicine, University of California San Diego, La Jolla, CA, USA.
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Microbiol Res. 2022 Dec;265:127205. doi: 10.1016/j.micres.2022.127205. Epub 2022 Sep 21.
Previous studies have suggested that dysbiosis of the gut microbiota is associated with the development of pulmonary hypertension (PH). In this study, we established a left pulmonary artery ligation (LPAL)-induced PH rat model due to high flow and hemodynamic stress and investigated the association between gut microbiota composition and host metabolome signatures (in both gut and lung tissues) by using multiomics and correlation analysis. The results showed that LPAL successfully induced PH, characterized by increased right ventricular systolic pressure, right ventricular hypertrophy and pulmonary vascular remodelling. Moreover, gut pathological abnormalities were observed in association with dramatic alterations in the gut microbiome and metabolome as well as the lung metabolome. The increased bacterial genus Sporobacter and decreased genera Eubacterium, Eubacteriaceae, Deltaproteobacteria and Desulfovibrio featured the altered gut microbiome in LPAL-PH versus SHAM rats. Moreover, imbalanced abundance of protective metabolites (e.g., butyrate, propionate) and pathogenic metabolites (e.g., proinflammatory mediators) were seen in the gut metabolome of LPAL-PH versus SHAM rats. In addition, the altered gut microbiome strongly correlated with the altered metabolome patterns in both the gut and lung of LPAL-PH rats. In conclusion, this study revealed significant gut dysbiosis in LPAL-PH rats, characterized by altered gut microbiota composition, in association with specific changes in gut and lung metabolome profiles. These findings enriched our understanding of the unique signature of the gut microbiome and the close association of the "gut-lung axis" in LPAL-PH induced by long-term high flow, leading to novel therapeutic, diagnostic or management paradigms for this subtype of PH.
先前的研究表明，肠道微生物群落失调与肺动脉高压（PH）的发展有关。在这项研究中，我们建立了左肺动脉结扎（LPAL）诱导的 PH 大鼠模型，由于高流量和血流动力学应激，通过多组学和相关分析，研究了肠道微生物群落组成与宿主代谢组特征（在肠道和肺部组织中）之间的关联。结果表明，LPAL 成功地诱导了 PH，表现为右心室收缩压升高、右心室肥厚和肺血管重塑。此外，观察到肠道病理异常与肠道微生物群和代谢组以及肺部代谢组的剧烈变化相关。与 SHAM 大鼠相比，LPAL-PH 大鼠的肠道微生物群中增加的细菌属 Sporobacter 和减少的属 Eubacterium、Eubacteriaceae、Deltaproteobacteria 和 Desulfovibrio 为特征。此外，在 LPAL-PH 大鼠的肠道代谢组中，保护性代谢物（如丁酸、丙酸盐）和致病性代谢物（如促炎介质）的丰度失衡。此外，改变的肠道微生物群与 LPAL-PH 大鼠的肠道和肺部的改变的代谢组模式密切相关。总之，这项研究揭示了 LPAL-PH 大鼠的显著肠道失调，其特征是肠道微生物群落组成的改变，与肠道和肺部代谢组谱的特定变化相关。这些发现丰富了我们对长期高流量诱导的 LPAL-PH 中肠道微生物群独特特征的理解，并密切关联了“肠-肺轴”，为这种 PH 亚型提供了新的治疗、诊断或管理模式。
