Division of Pulmonary and Critical Care Medicine, Department of Medicine.
Department of Pharmaceutical Sciences, University of Colorado, Anschutz Campus, Aurora, Colorado.
Am J Respir Crit Care Med. 2022 Aug 15;206(4):427-439. doi: 10.1164/rccm.202110-2241OC.
Chronic obstructive pulmonary disease (COPD) is variable in its development. Lung microbiota and metabolites collectively may impact COPD pathophysiology, but relationships to clinical outcomes in milder disease are unclear. Identify components of the lung microbiome and metabolome collectively associated with clinical markers in milder stage COPD. We analyzed paired microbiome and metabolomic data previously characterized from bronchoalveolar lavage fluid in 137 participants in the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study), or (GOLD [Global Initiative for Chronic Obstructive Lung Disease Stage 0-2). Datasets used included ) bacterial 16S rRNA gene sequencing; ) untargeted metabolomics of the hydrophobic fraction, largely comprising lipids; and ) targeted metabolomics for a panel of hydrophilic compounds previously implicated in mucoinflammation. We applied an integrative approach to select features and model 14 individual clinical variables representative of known associations with COPD trajectory (lung function, symptoms, and exacerbations). The majority of clinical measures associated with the lung microbiome and metabolome collectively in overall models (classification accuracies, >50%, < 0.05 vs. chance). Lower lung function, COPD diagnosis, and greater symptoms associated positively with , , and , together with compounds from several classes (glycosphingolipids, glycerophospholipids, polyamines and xanthine, an adenosine metabolite). In contrast, several members, together with adenosine, 5'-methylthioadenosine, sialic acid, tyrosine, and glutathione, associated with better lung function, absence of COPD, or less symptoms. Significant correlations were observed between specific metabolites and bacteria ( < 0.05). Components of the lung microbiome and metabolome in combination relate to outcome measures in milder COPD, highlighting their potential collaborative roles in disease pathogenesis.
慢性阻塞性肺疾病（COPD）的发展具有变异性。肺部微生物群和代谢物可能共同影响 COPD 的病理生理学，但与轻度疾病的临床结局的关系尚不清楚。确定与轻度 COPD 临床标志物相关的肺部微生物组和代谢组的综合组成部分。我们分析了先前在 SPIROMICS（COPD 亚群和中间结局测量研究）或（GOLD [慢性阻塞性肺疾病全球倡议 0-2 期）中支气管肺泡灌洗液中特征化的肺部微生物组和代谢组学的配对数据。使用的数据集包括）细菌 16S rRNA 基因测序；）疏水性部分的非靶向代谢组学，主要包括脂质；和）先前涉及粘蛋白炎症的一组亲水性化合物的靶向代谢组学。我们应用综合方法选择特征并对 14 个代表与 COPD 轨迹（肺功能、症状和加重）相关的已知关联的个体临床变量进行建模。在整体模型中，大多数与肺部微生物群和代谢物相关的临床测量值与整体模型相关（分类准确率，>50%，<0.05 与机会相比）。较低的肺功能、COPD 诊断和更大的症状与，和，以及来自几个类别的化合物（糖脂、甘油磷脂、多胺和黄嘌呤、腺苷代谢物）呈正相关。相比之下，一些成员，以及腺苷、5'-甲基硫代腺苷、唾液酸、酪氨酸和谷胱甘肽，与更好的肺功能、没有 COPD 或较少的症状相关。观察到特定代谢物与细菌之间存在显著相关性（<0.05）。肺部微生物组和代谢组的综合成分与轻度 COPD 的结局测量值相关，突出了它们在疾病发病机制中的潜在协同作用。
