Stewart Christopher J, Mansbach Jonathan M, Wong Matthew C, Ajami Nadim J, Petrosino Joseph F, Camargo Carlos A, Hasegawa Kohei
1 Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas; and.
2 Department of Medicine, Boston Children's Hospital, and.
Am J Respir Crit Care Med. 2017 Oct 1;196(7):882-891. doi: 10.1164/rccm.201701-0071OC.
Bronchiolitis is the most common lower respiratory infection in infants; however, it remains unclear which infants with bronchiolitis will develop severe illness. In addition, although emerging evidence indicates associations of the upper-airway microbiome with bronchiolitis severity, little is known about the mechanisms linking airway microbes and host response to disease severity.
To determine the relations among the nasopharyngeal airway metabolome profiles, microbiome profiles, and severity in infants with bronchiolitis.
We conducted a multicenter prospective cohort study of infants (age <1 yr) hospitalized with bronchiolitis. By applying metabolomic and metagenomic (16S ribosomal RNA gene and whole-genome shotgun sequencing) approaches to 144 nasopharyngeal airway samples collected within 24 hours of hospitalization, we determined metabolome and microbiome profiles and their association with higher severity, defined by the use of positive pressure ventilation (i.e., continuous positive airway pressure and/or intubation).
Nasopharyngeal airway metabolome profiles significantly differed by bronchiolitis severity (P < 0.001). Among 254 metabolites identified, a panel of 25 metabolites showed high sensitivity (84%) and specificity (86%) in predicting the use of positive pressure ventilation. The intensity of these metabolites was correlated with relative abundance of Streptococcus pneumoniae. In the pathway analysis, sphingolipid metabolism was the most significantly enriched subpathway in infants with positive pressure ventilation use compared with those without (P < 0.001). Enrichment of sphingolipid metabolites was positively correlated with the relative abundance of S. pneumoniae.
Although further validation is needed, our multiomic analyses demonstrate the potential of metabolomics to predict bronchiolitis severity and better understand microbe-host interaction.
细支气管炎是婴儿中最常见的下呼吸道感染；然而，目前尚不清楚哪些患细支气管炎的婴儿会发展为重症疾病。此外，尽管新出现的证据表明上呼吸道微生物群与细支气管炎严重程度有关，但对于气道微生物与宿主对疾病严重程度反应之间的联系机制知之甚少。
确定细支气管炎婴儿的鼻咽气道代谢组谱、微生物组谱与疾病严重程度之间的关系。
我们对因细支气管炎住院的婴儿（年龄<1岁）进行了一项多中心前瞻性队列研究。通过对住院24小时内收集的144份鼻咽气道样本应用代谢组学和宏基因组学方法（16S核糖体RNA基因和全基因组鸟枪法测序），我们确定了代谢组和微生物组谱及其与更高疾病严重程度的关联，疾病严重程度通过使用正压通气来定义（即持续气道正压通气和/或插管）。
鼻咽气道代谢组谱因细支气管炎严重程度而异（P<0.001）。在鉴定出的254种代谢物中，一组25种代谢物在预测正压通气的使用方面显示出高灵敏度（84%）和特异性（86%）。这些代谢物的强度与肺炎链球菌的相对丰度相关。在通路分析中，与未使用正压通气的婴儿相比，使用正压通气的婴儿中鞘脂代谢是最显著富集的子通路（P<0.001）。鞘脂代谢物的富集与肺炎链球菌的相对丰度呈正相关。
尽管需要进一步验证，但我们的多组学分析证明了代谢组学在预测细支气管炎严重程度和更好理解微生物-宿主相互作用方面的潜力。
