Data_Sheet_1_Altered Lung Microbiome and Metabolome Profile in Children With Pulmonary Arterial Hypertension Associated With Congenital Heart Disease.pdf

BackgroundsPulmonary arterial hypertension (PAH) is characterized by progressive pulmonary vascular functional and structural changes, resulting in increased pulmonary vascular resistance and eventually right heart failure and death. Congenital Left-to-Right shunts (LTRS) is one type of congenital heart disease (CHD) and PAH associated with the congenital Left-to-Right shunt (PAH-LTRS) is a severe disease in children. However, changes in the lung microbiome and their potential impact on PAH-LTRS have not been not fully studied. We hypothesized that lung microbiota and their derived metabolites have been disturbed in children with PAH-LTRS, which might contribute to the progression and outcomes of PAH-LTRS.
MethodsIn this study, 68 age- and sex-matched children of three different groups (patients with PAH-LTRS cohort, patients with LTRS but have no pathologic features of PAH cohort, and healthy reference cohort) were enrolled in the current study. Bronchoalveolar lavage fluid samples from these participants were conducted for multi-omics analysis, including 16S rRNA sequencing and metabolomic profiling. Data progressing and integration analysis were performed to identify pulmonary microbial and metabolic characteristics of PAH-LTRS in children.
ResultsWe found that microbial community density was not significantly altered in PAH-LTRS based on α-diversity analysis. Microbial composition analysis indicated phylum of Bacteroidetes was that less abundant while Lactobacillus, Alicycliphilus, and Parapusillimonas were significantly altered and might contribute to PAH in children with LTRS. Moreover, metabolome profiling data showed that metabolites involved in Purine metabolism, Glycerophospholipid metabolism, Galactose metabolism, and Pyrimidine metabolism were also significantly disturbed in the PAH-LTRS cohort. Correlation analysis between microbes and metabolites indicated that alterations in the microbial composition from the lung microbiota could eventually result in the disturbance in certain metabolites, and might finally contribute to the pathology of PAH-LTRS.
ConclusionLung microbial density was not significantly altered in patients with PAH-LTRS. Composition analysis results showed that the relative microbiome abundance was different between groups. Metabolome profiling and correlation analysis with microbiota showed that metabolome also altered in children with PAH-LTRS. This study indicated that pulmonary microbes and metabolites disturbed in PAH-LTRS could be potentially effective biomarkers and provides valuable perspectives on clinical diagnosis, treatment, and prognosis of pediatric PAH-LTRS.

研究背景：肺动脉高压（PAH）以进行性肺血管功能与结构改变为特征，可导致肺血管阻力升高，最终引发右心衰竭乃至死亡。先天性左向右分流（LTRS）属于先天性心脏病（CHD）的一类，合并先天性左向右分流的肺动脉高压（PAH-LTRS）是儿童群体中的重症疾病。然而目前针对肺部菌群变化及其对PAH-LTRS的潜在影响尚未得到充分研究。本研究提出假设：PAH-LTRS患儿的肺部菌群及其衍生代谢产物存在紊乱，且该紊乱可能参与PAH-LTRS的病情进展与转归过程。
研究方法：本研究共纳入68名年龄与性别匹配的儿童，分为3组：PAH-LTRS患儿队列、仅存在左向右分流但无肺动脉高压病理特征患儿队列，以及健康对照队列。采集所有受试者的支气管肺泡灌洗液样本，开展多组学分析，包括16S rRNA测序与代谢组学表征。通过数据处理与整合分析，明确儿童PAH-LTRS的肺部菌群与代谢特征。
研究结果：基于α多样性分析，本研究发现PAH-LTRS患儿的肺部菌群群落密度无显著改变。菌群组成分析显示，拟杆菌门（Bacteroidetes）丰度降低，而乳杆菌属（Lactobacillus）、环脂芽孢杆菌属（Alicycliphilus）以及副微小杆菌属（Parapusillimonas）的丰度发生显著改变，且可能参与左向右分流相关儿童肺动脉高压的发病过程。此外，代谢组学表征数据显示，PAH-LTRS队列中涉及嘌呤代谢、甘油磷脂代谢、半乳糖代谢以及嘧啶代谢的代谢产物均存在显著紊乱。菌群与代谢产物的关联分析表明，肺部菌群组成的改变可最终引发特定代谢产物的紊乱，并可能参与PAH-LTRS的病理生理过程。
研究结论：PAH-LTRS患者的肺部菌群密度无显著改变。菌群组成分析结果显示，各组间的菌群相对丰度存在差异。代谢组学表征及菌群关联分析显示，PAH-LTRS患儿的代谢组同样存在异常。本研究表明，PAH-LTRS中发生紊乱的肺部菌群与代谢产物有望成为有效的生物标志物，同时为儿童PAH-LTRS的临床诊断、治疗及预后评估提供了具有价值的研究视角。