特发性肺动脉高压肠道菌群-宿主共代谢研究

Idiopathic pulmonary arterial hypertension(IPAH) is a kind of pulmonary vascular disease with poor prognosis, its etiology and pathogenesis is not yet entirely clear. Gut microbiota plays an important role in cardiovascular disease, some studies showed that gut microbiota may play an important role in pulmonary vascular disease and pulmonary arterial hypertension. There is a cometabolism process between gut microbiota and host. This study will collect fecal and plasma samples from healthy controls and patients with IPAH, analysis of the gut microbiome by sequencing of the amplicon targeting the V3–V4 region of the 16S rRNA gene, some fecal samples will be analyzed by using deep metagenomic sequencing, fecal and plasma samples will be analyzed by metabonomics. Observe the changes of gut microbiota and host co-metabolism in normal group and patients with IPAH; analysis of metabolites, identify potential biomarkers, analysis of the relationship between metabolites and the structure, composition of gut microbiota. This study is the first to explore the mechanism of IPAH from the perspective of gut microbiota and host metabolism, which is helpful to promote the understanding of this disease, and is expected to provide a new theoretical basis for the prevention and treatment of the disease.

特发性肺动脉高压是一类预后恶劣的肺血管疾病，其发病机制尚未清楚。肠道菌群在心血管疾病中起着重要作用，有研究间接提示肠道菌群可能在肺血管疾病和肺动脉高压中起着重要作用。肠道菌群和宿主间存在共代谢过程。本课题将收集健康对照组、特发性肺动脉高压患者的粪便及血浆样本，对肠道菌群进行16S rRNA V3-V4区扩增、测序及生物信息学分析，对部分样本进行宏基因组深度测序分析，进行粪便、血浆样本代谢组学检测分析。观察正常组、特发性肺动脉高压患者肠道菌群及宿主共代谢产物的变化；对代谢产物进行分析，找出潜在生物标记物，并分析其与肠道菌群结构和组成的关联。本课题创新性从肠道菌群与宿主代谢角度探讨特发性肺动脉高压的发病机制，有利于促进对该疾病的认识，有望为该病的防治提供新的理论依据和新的治疗靶点。

特发性肺动脉高压是一类预后恶劣的肺血管疾病，其发病机制尚未清楚。肠道菌群在心血管疾病中起着重要作用，肠道菌群和宿主间存在共代谢过程。有研究提示肠道菌群可能在肺血管疾病和肺动脉高压中起着重要作用。本课题拟观察特发性肺动脉高压患者肠道菌群及血浆样本代谢组情况。我们收集了特发性肺动脉高压患者的粪便和血浆样本,把特发性肺动脉高压患者粪便样本进行了宏基因组测序分析，在特发性肺动脉高压患者的血浆中，进行了靶向代谢组学检测分析。发现特发性肺动脉高压患者与健康对照组在门水平与属水平上菌种组成存在差异；在门水平上，健康对照中厚壁菌门相对丰度高，而在特发性肺动脉高压组，拟杆菌门相对丰度高；在属水平上，特发性肺动脉高压组拟杆菌属相对丰度高。将细菌差异基因功能富集于KEGG通路数据库之上，共发现16条在特发性肺动脉高压患者与健康对照之间表达有差异的通路。差异最大的通路是ko02010 ABC transporters通路。靶向代谢组学检测分析发现特发性肺动脉高压患者中有4种代谢物显著下调，14种代谢物显著上调。该研究结果有助于揭示特发性肺动脉高压的发病机制，有助于为特发性肺动脉高压治疗提供新的靶点。