Chiu Chih-Yung, Chou Hsin-Cheng, Chang Lun-Ching, Fan Wen-Lang, Dinh Michael Cong Vinh, Kuo Yu-Lun, Chung Wen-Hung, Lai Hsin-Chih, Hsieh Wen-Ping, Su Shih-Chi
Division of Pediatric Pulmonology, Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Clinical Metabolomics Core Laboratory, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
Allergy. 2020 Nov;75(11):2846-2857. doi: 10.1111/all.14438. Epub 2020 Jul 13.
Childhood asthma is a multifactorial inflammatory condition of the airways, associated with specific changes in respiratory microbiome and circulating metabolome.
To explore the functional capacity of asthmatic microbiome and its intricate connection with the host, we performed shotgun sequencing of airway microbiome and untargeted metabolomics profiling of serum samples in a cohort of children with mite-sensitized asthma and non-asthmatic controls.
We observed higher gene counts and sample-to-sample dissimilarities in asthmatic microbiomes, indicating a more heterogeneous community structure and functionality among the cases than in controls. Moreover, we identified airway microbial species linked to changes in circulating metabolites and IgE responses of the host, including a positive correlation between Prevotella sp oral taxon 306 and dimethylglycine that were both decreased in patients. Several control-enriched species (Eubacterium sulci, Prevotella pallens, and Prevotella sp oral taxon 306) were inversely correlated with total and allergen-specific IgE levels. Genes related to microbial carbohydrate, amino acid, and lipid metabolism were differentially enriched, suggesting that changes in microbial metabolism may contribute to respiratory health in asthmatics. Pathway modules relevant to allergic responses were differentially abundant in asthmatic microbiome, such as enrichments for biofilm formation by Pseudomonas aeruginosa, membrane trafficking, histidine metabolism, and glycosaminoglycan degradation, and depletions for polycyclic aromatic hydrocarbon degradation. Further, we identified metagenomic and metabolomic markers (eg, Eubacterium sulci) to discriminate cases from the non-asthmatic controls.
Our dual-omics data reveal the connections between respiratory microbes and circulating metabolites perturbed in mite-sensitized pediatric asthma, which may be of etiological and diagnostic implications.
儿童哮喘是一种气道的多因素炎症性疾病，与呼吸道微生物组和循环代谢组的特定变化有关。
为了探究哮喘微生物组的功能能力及其与宿主的复杂联系，我们对一组尘螨致敏哮喘儿童和非哮喘对照儿童的气道微生物组进行了鸟枪法测序，并对血清样本进行了非靶向代谢组学分析。
我们观察到哮喘微生物组中的基因计数更高，且样本间差异更大，这表明与对照组相比，病例组的群落结构和功能更加异质。此外，我们鉴定出与宿主循环代谢物变化和IgE反应相关的气道微生物种类，包括普氏菌属口腔分类群306与二甲基甘氨酸之间的正相关，二者在患者中均降低。几种对照组富集的物种（龈真杆菌、苍白普氏菌和普氏菌属口腔分类群306）与总IgE水平和过敏原特异性IgE水平呈负相关。与微生物碳水化合物、氨基酸和脂质代谢相关的基因存在差异富集，这表明微生物代谢的变化可能有助于哮喘患者的呼吸健康。与过敏反应相关的通路模块在哮喘微生物组中丰度不同，例如铜绿假单胞菌生物膜形成、膜运输、组氨酸代谢和糖胺聚糖降解的富集，以及多环芳烃降解的减少。此外，我们鉴定出宏基因组和代谢组学标志物（如龈真杆菌）以区分病例组和非哮喘对照组。
我们的双组学数据揭示了尘螨致敏儿童哮喘中呼吸道微生物与循环代谢物之间的联系，这可能具有病因学和诊断学意义。
