Nasopharyngeal airway dual-transcriptome of infants with severe bronchiolitis and risk of childhood asthma: A multicenter prospective study.

Nasopharyngeal airway dual-transcriptome of infants with severe bronchiolitis and risk of childhood asthma: A multicenter prospective study.
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严重毛细支气管炎与儿童哮喘风险的鼻咽呼吸道双转录组:一项多中心前瞻性研究。

DOI:
10.1016/j.jaci.2022.04.017
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发表时间:
2022-10
影响因子:
14.2
通讯作者:
Hasegawa, Kohei
Hasegawa, Kohei
中科院分区:
医学1区
文献类型:
--
作者:
Zhu, Zhaozhong;Camargo, Carlos A., Jr.;Raita, Yoshihiko;Freishtat, Robert J.;Fujiogi, Michimasa;Hahn, Andrea;Mansbach, Jonathan M.;Spergel, Jonathan M.;Perez-Losada, Marcos;Hasegawa, Kohei

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婴儿期的严重毛细支气管炎(即需要住院的毛细支气管炎)是儿童哮喘的主要危险因素。然而,将这些常见疾病联系起来的确切机制仍不清楚。研究呼吸道微生物群(包括分类和功能)和宿主反应在这一高危人群哮喘发展中的综合作用。在一项多中心前瞻性队列研究中,244名患有严重毛细支气管炎的婴儿(中位年龄,3个月),我们检查了他们住院时的鼻咽转录组(微生物组)、转录组(宿主)和代谢组。我们调查了1)主要细菌种类(肺炎链球菌、流感嗜血杆菌和卡他莫拉菌),2)微生物功能,以及3)宿主反应与6岁前发生哮喘的风险的纵向关系。首先,肺炎链球菌的数量与哮喘的风险相关(P=0.01),特别是在非鼻病毒感染的婴儿中(P=0.04)。第二,在328条因哮喘的发生而差异丰富的微生物功能途径中,最重要的途径(例如,脂肪酸和糖酵解途径;fdr<1×10−12)是由这三个主要物种驱动的(例如,肺炎链球菌与糖酵解的正相关性;fdr<0.001)。利用平行代谢组数据对这些微生物功能途径进行了验证。第三,有104条转录组途径被差异增强(FDR&lt0.05)--例如,干扰素-α和-γ下调,T细胞激活通路上调。肺炎链球菌与大多数差异表达的转录本相关(例如,DAGLB;FDR<0.05)。通过应用转录组学、转录组学和代谢组学方法对毛细支气管炎患儿进行多中心队列研究,我们发现了主要细菌种类、功能和呼吸道宿主反应之间的相互作用,以及它们与哮喘发生的纵向关系。在毛细支气管炎住院的婴儿中,对鼻咽双转录组和代谢组数据的综合组学分析发现,呼吸道微生物组(分类和功能)和宿主反应之间存在相互作用,以及它们与哮喘发生的关系。
Severe bronchiolitis (i.e., bronchiolitis requiring hospitalization) during infancy is a major risk factor for childhood asthma. However, the exact mechanism linking these common conditions remains unclear. To examine the integrated role of airway microbiome (both taxonomy and function) and host response in asthma development in this high-risk population. In a multicenter prospective cohort study of 244 infants with severe bronchiolitis (median age, 3 months), we examined their nasopharyngeal metatranscriptome (microbiome) and transcriptome (host), and metabolome at hospitalization. We investigated the longitudinal relationship of 1) major bacterial species (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis), 2) microbial function, and 3) host response with risks of developing asthma by age 6 years. First, the abundance of S. pneumoniae was associated with greater risks of asthma (P=0.01), particularly in infants with non-rhinovirus infection (Pinteraction=0.04). Second, of 328 microbial functional pathways differentially-enriched by asthma development, the top pathways (e.g., fatty acid and glycolysis pathways; FDR<1×10−12) were driven by these three major species (e.g., positive association of S. pneumoniae with glycolysis; FDR<0.001). These microbial functional pathways were validated with the parallel metabolome data. Third, 104 transcriptome pathways were differentially-enriched (FDR<0.05)—e.g., downregulated interferon-α and -γ and upregulated T cell activation pathways. S. pneumoniae was associated with most differentially-expressed transcripts (e.g., DAGLB; FDR<0.05). By applying metatranscriptomics, transcriptomics, and metabolomics approaches to a multicenter cohort of infants with bronchiolitis, we found an interplay between major bacterial species, their function, and host response in the airway, and their longitudinal relationship with asthma development. Among infants hospitalized with bronchiolitis, an integrated omics analysis of the nasopharyngeal dual-transcriptome and metabolome data identified an interplay between the airway microbiome (both taxonomy and function) and host response and their relationship with asthma development.
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