Microbiome and metabolome dysbiosis of the gut-lung axis in pulmonary hypertension
Microbiome and metabolome dysbiosis of the gut-lung axis in pulmonary hypertension
复制标题
肺动脉高压时肠道-肺轴的微生物组和代谢组学异常
DOI：
10.1016/j.micres.2022.127205
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发表时间：
2022-10-04
影响因子：
6.7
通讯作者：
Wang, Jian
中科院分区：
文献类型：
--
作者：
Chen, Jiyuan;Zhou, Dansha;Wang, Jian
先前的研究表明，肠道微生物群的生态失调与肺动脉高压（PH）的发展有关。在本研究中，我们建立了左肺动脉结扎（LPAL）诱导的高流量和血流动力学应激的PH大鼠模型，并通过多组学和相关分析研究了肠道微生物群组成与宿主（肠道和肺组织）代谢组特征之间的关系。结果显示，LPAL成功诱导大鼠PH，表现为右心室收缩压升高、右心室肥厚、肺血管重构。此外，观察到肠道病理异常与肠道微生物组和代谢组以及肺代谢组的显著改变有关。与SHAM相比，LPAL-PH大鼠的肠道微生物群发生了改变，孢子杆菌属增加，真杆菌属、真杆菌科、三角洲变形杆菌属和脱硫弧菌属减少。此外，与SHAM相比，LPAL-PH大鼠肠道代谢组中保护性代谢物（如丁酸盐、丙酸盐）和致病性代谢物（如促炎介质）的丰度不平衡。此外，肠道微生物组的改变与LPAL-PH大鼠肠道和肺部代谢组模式的改变密切相关。总之，本研究揭示了LPAL-PH大鼠明显的肠道生态失调，其特征是肠道微生物群组成的改变，与肠道和肺代谢组谱的特定变化有关。这些发现丰富了我们对肠道微生物组独特特征的理解，以及长期高流量诱导的LPAL-PH中“肠-肺轴”的密切关联，从而为这种PH亚型提供了新的治疗、诊断或管理范例。
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 patho-genic 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.