宏基因组学联合代谢组学共同揭示螨过敏儿童哮喘患者气道微生物群的特定特征及功能
2021/12/03
摘要
背景：儿童哮喘是一种多因素的气道炎症疾病，与呼吸道微生物组和循环代谢组的特定变化有关。
方法：为了探索哮喘患者气道微生物组的功能及其与宿主的错综复杂关系，我们对螨过敏性哮喘儿童和非哮喘对照儿童进行了气道微生物的鸟枪法宏基因组测序和血清样本的非靶向代谢组学分析。
结果：我们发现哮喘患者气道样本中测得的基因数更多，样本间差异更大。这说明与对照组相比，哮喘患者的气道微生物群落结构与功能更具异质性。此外，我们确定了与循环代谢物变化和宿主 IgE 反应相关的气道微生物种类，同时我们还发现了Prevotella sp oral taxon 306和二甲基甘氨酸之间的正相关关系，而且发现这两者在哮喘患者体内均减少。对照组人群气道富集的微生物物种（包括Eubacterium sulci, Prevotella pallens, and Prevotella sp oral taxon 306）与血液总 IgE 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在两组间富集差异明显，这说明微生物代谢的变化可能与哮喘患者的呼吸系统健康状态改变有关。与过敏反应相关的通路模块在哮喘患者及对照组中富集情况也有差异，例如铜绿假单胞菌相关的生物膜形成、跨膜转运、组氨酸代谢和糖胺聚糖降解，以及多环芳烃降解等通路模块。此外，我们还确定了用以区分哮喘组与非哮喘对照组的宏基因组和代谢组学标记（例如Eubacterium sulci）。
结论：我们的双组学数据揭示了螨过敏儿童哮喘中呼吸道微生物和循环代谢物之间的联系，这可能具有病因学与诊断意义。
Integration of metagenomics-metabolomics reveals specific signatures and functions of airway microbiota in mite-sensitized childhood asthma
Chiu CY, Chou HC, Chang LC, Fan WL, Dinh MCV, Kuo YL, Chung WH, Lai HC, Hsieh WP, Su SC.
Allergy. 2020 Nov;75(11):2846-2857. doi: 10.1111/all.14438. PMID: 32506557.
Abstract
Background: Childhood asthma is a multifactorial inflammatory condition of the airways, associated with specific changes in respiratory microbiome and circulating metabolome.
Methods: 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.
Results: 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.
Conclusions: 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.
背景：儿童哮喘是一种多因素的气道炎症疾病，与呼吸道微生物组和循环代谢组的特定变化有关。
方法：为了探索哮喘患者气道微生物组的功能及其与宿主的错综复杂关系，我们对螨过敏性哮喘儿童和非哮喘对照儿童进行了气道微生物的鸟枪法宏基因组测序和血清样本的非靶向代谢组学分析。
结果：我们发现哮喘患者气道样本中测得的基因数更多，样本间差异更大。这说明与对照组相比，哮喘患者的气道微生物群落结构与功能更具异质性。此外，我们确定了与循环代谢物变化和宿主 IgE 反应相关的气道微生物种类，同时我们还发现了Prevotella sp oral taxon 306和二甲基甘氨酸之间的正相关关系，而且发现这两者在哮喘患者体内均减少。对照组人群气道富集的微生物物种（包括Eubacterium sulci, Prevotella pallens, and Prevotella sp oral taxon 306）与血液总 IgE 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在两组间富集差异明显，这说明微生物代谢的变化可能与哮喘患者的呼吸系统健康状态改变有关。与过敏反应相关的通路模块在哮喘患者及对照组中富集情况也有差异，例如铜绿假单胞菌相关的生物膜形成、跨膜转运、组氨酸代谢和糖胺聚糖降解，以及多环芳烃降解等通路模块。此外，我们还确定了用以区分哮喘组与非哮喘对照组的宏基因组和代谢组学标记（例如Eubacterium sulci）。
结论：我们的双组学数据揭示了螨过敏儿童哮喘中呼吸道微生物和循环代谢物之间的联系，这可能具有病因学与诊断意义。
(李仁娇2 张红萍1 王刚2 四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（Allergy. 2020 Nov;75(11):2846-2857. doi: 10.1111/all.14438. PMID: 32506557.）
（Allergy. 2020 Nov;75(11):2846-2857. doi: 10.1111/all.14438. PMID: 32506557.）
Integration of metagenomics-metabolomics reveals specific signatures and functions of airway microbiota in mite-sensitized childhood asthma
Chiu CY, Chou HC, Chang LC, Fan WL, Dinh MCV, Kuo YL, Chung WH, Lai HC, Hsieh WP, Su SC.
Allergy. 2020 Nov;75(11):2846-2857. doi: 10.1111/all.14438. PMID: 32506557.
Abstract
Background: Childhood asthma is a multifactorial inflammatory condition of the airways, associated with specific changes in respiratory microbiome and circulating metabolome.
Methods: 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.
Results: 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.
Conclusions: 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.
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上皮galectin-13表达增加与哮喘嗜酸粒细胞性气道炎症有关
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基层医疗中哮喘和COPD客观检测的障碍和促成因素：一项使用理论领域框架的系统综述
