Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas.
Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom.
J Infect Dis. 2019 May 24;219(12):2005-2014. doi: 10.1093/infdis/jiz021.
Emerging evidence suggests relationships between the nasopharyngeal metabolome and both the microbiota and severity of bronchiolitis. However, the influence of host systemic metabolism on disease pathobiology remains unclear. We aimed to examine metabolome profiles and their association with more-severe disease, defined by use of positive pressure ventilation (PPV), in infants hospitalized for bronchiolitis.
In 140 infants with bronchiolitis, metabolomic profiling was performed on serum; samples from 70 were in a training data set, and samples from 70 were in an independent test data set. We also profiled the nasopharyngeal airway microbiota and examined its association with the serum metabolites.
Serum metabolome profiles differed by bronchiolitis severity (P < .001). In total, 20 metabolites in the training data set were significantly associated with the risk of PPV, of which 18 remained significant following adjustment for confounders (false-discovery rate [FDR], < 0.10). Phosphatidylcholine metabolites were associated with higher risks of PPV use, while metabolites from the plasmalogen subpathway were associated with lower risks. The test data set validated these findings (FDR < 0.05). Streptococcus abundance was positively associated with metabolites that are associated with higher risks of PPV.
Serum metabolomic signatures were associated with both the nasopharyngeal microbiota and the severity of bronchiolitis. Our findings advance research into the complex interrelations between the airway microbiome, host systemic response, and pathobiology of bronchiolitis.
新出现的证据表明,鼻咽代谢组与微生物群和毛细支气管炎的严重程度之间存在关系。然而,宿主系统代谢对疾病病理生物学的影响尚不清楚。我们旨在检查代谢组谱及其与更严重疾病的关联,更严重的疾病通过使用正压通气(PPV)来定义,在因毛细支气管炎住院的婴儿中。
在 140 名毛细支气管炎婴儿中,对血清进行代谢组学分析;70 份样本来自训练数据集,70 份样本来自独立测试数据集。我们还对鼻咽气道微生物群进行了分析,并研究了其与血清代谢物的关联。
血清代谢组谱因毛细支气管炎严重程度而异(P <.001)。在训练数据集中,有 20 种代谢物与使用 PPV 的风险显著相关,其中 18 种代谢物在调整混杂因素后仍然具有显著意义(错误发现率[FDR],< 0.10)。磷脂酰胆碱代谢物与更高的 PPV 使用风险相关,而来自类脂素亚途径的代谢物与更低的风险相关。测试数据集验证了这些发现(FDR < 0.05)。链球菌丰度与与更高的 PPV 使用风险相关的代谢物呈正相关。
血清代谢组学特征与鼻咽微生物群和毛细支气管炎的严重程度均相关。我们的研究结果推进了气道微生物群、宿主系统反应和毛细支气管炎病理生物学之间复杂相互关系的研究。