Ma Runwei, Cheng Liming, Song Yi, Sun Yi, Gui Wenting, Deng Yao, Xie Chao, Liu Min
Department of Cardiovascular Surgery, Fuwai Yunnan Cardiovascular Hospital, Kunming, China.
Department of Anesthesiology, Kunming Children's Hospital, Kunming, China.
Front Med (Lausanne). 2022 Jul 28;9:940784. doi: 10.3389/fmed.2022.940784. eCollection 2022.
Pulmonary 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.
In 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.
We 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.
Lung 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.
肺动脉高压（PAH）的特征是肺血管功能和结构逐渐发生变化，导致肺血管阻力增加，最终引发右心衰竭和死亡。先天性左向右分流（LTRS）是先天性心脏病（CHD）的一种类型，与先天性左向右分流相关的肺动脉高压（PAH-LTRS）是儿童中的一种严重疾病。然而，肺微生物群的变化及其对PAH-LTRS的潜在影响尚未得到充分研究。我们假设PAH-LTRS患儿的肺微生物群及其衍生代谢产物受到干扰，这可能有助于PAH-LTRS的进展和预后。
在本研究中，纳入了68名年龄和性别匹配的来自三个不同组的儿童（PAH-LTRS队列患者、有LTRS但无PAH病理特征的队列患者以及健康对照队列）。对这些参与者的支气管肺泡灌洗液样本进行多组学分析，包括16S rRNA测序和代谢组学分析。进行数据处理和整合分析，以确定儿童PAH-LTRS的肺部微生物和代谢特征。
基于α多样性分析，我们发现PAH-LTRS中的微生物群落密度没有显著改变。微生物组成分析表明，拟杆菌门的丰度较低，而乳酸杆菌属、嗜环脂菌属和副小单胞菌属有显著变化，可能与LTRS患儿的PAH有关。此外，代谢组学分析数据显示，参与嘌呤代谢、甘油磷脂代谢、半乳糖代谢和嘧啶代谢的代谢产物在PAH-LTRS队列中也受到显著干扰。微生物与代谢产物之间的相关性分析表明，肺微生物群的微生物组成变化最终可能导致某些代谢产物的紊乱，并最终可能导致PAH-LTRS的病理改变。
PAH-LTRS患者的肺微生物密度没有显著改变。组成分析结果表明，不同组之间微生物组的相对丰度不同。代谢组学分析以及与微生物群的相关性分析表明，PAH-LTRS患儿的代谢组也发生了改变。本研究表明，PAH-LTRS中受干扰的肺部微生物和代谢产物可能是潜在的有效生物标志物，并为儿童PAH-LTRS的临床诊断、治疗和预后提供了有价值的观点。
