代谢型与未控制儿童哮喘、肠道微生物群和全身炎症相关性研究
2025/04/30
摘要
背景：儿童哮喘与不同的代谢组学特征有关。
目的：通过粪便和血清代谢组综合分析，确定中重度哮喘儿童的表型（代谢型）。
方法：从全球哮喘治疗倡议≥3级的未控制儿童哮喘队列的系统药理学方法项目中招募儿童。哮喘控制通过哮喘控制测试和年度急性发作史定义。使用液相色谱和流动注射电喷雾电离三重四极杆质谱对粪便和血清进行靶向代谢组学分析。相似性网络融合整合了粪便和血清代谢组谱，然后进行光谱聚类。对聚类进行了哮喘特征、食物日记、粪便微生物群组成以及血清炎症标志物和血细胞水平的差异分析。
结果：对92名中重度哮喘儿童（中位年龄：11.5岁，34%为女性）的粪便和血清代谢组综合分析揭示了三种代谢型。代谢型1的变应性鼻炎发病率最低，血清神经酰胺和甘油三酯升高。代谢型2具有更高的哮喘控制几率，母乳喂养≥4个月的儿童比例最高，糖摄入量减少，血液中性粒细胞和血清炎症标志物水平最低，血清酰基肉碱和ω-3脂肪酸水平升高。代谢型3包括最高比例的未控制哮喘患者，血清胆固醇酯、磷脂酰胆碱和鞘磷脂降低，粪便氨基酸升高，粪便微生物群多样性降低。
结论：中重度哮喘儿童的代谢型与哮喘控制、不同的粪便微生物群和全身炎症模式有关。研究结果表明，代谢分型在哮喘的精准医学方法中具有重要价值。
Metabotypes are linked to uncontrolled childhood asthma, gut microbiota, and systemic inflammation.
Abdel-Aziz MI, Hashimoto S, Neerincx AH, Haarman EG, Cecil A, Lintelmann J, Witting M, Hauck SM, Kerssemakers N, Verster JC, Bang C, Franke A, Dierdorp BS, Dekker T, Metwally NKA, Duitman JW, Lutter R, Gorenjak M, Toncheva AA, Kheiroddin P, Harner S, Brandstetter S, Wolff C, Corcuera-Elosegui P, López-Fernández L, Perez-Garcia J, Almeida MM, Sardón-Prado O, Pino-Yanes M, Potočnik U, Kabesch M, Vijverberg SJH, Kraneveld AD, Maitland-van der Zee AH; SysPharmPediA consortium.
Abstract
BACKGROUND:Childhood asthma has been linked to distinct metabolomic profiles.
OBJECTIVES:To identify phenotypes (metabotypes) in children with moderate-to-severe asthma through integrative fecal and serum metabolome analysis.
METHODS:Children from the Systems Pharmacology Approach to Uncontrolled Pediatric Asthma cohort with Global Initiative for Asthma treatment step ≥3 were recruited. Asthma control was defined by the Asthma Control Test and annual exacerbation history. Targeted metabolomics profiling of feces and serum was performed using liquid chromatography and flow injection electrospray ionization-triple quadrupole mass spectrometry. Similarity Network Fusion integrated fecal and serum metabolome profiles, followed by spectral clustering. Clusters were analyzed for differences in asthma characteristics, food diaries, fecal microbiota composition, and levels of serum inflammatory markers and blood cells.
RESULTS:Prebronchodilator (trough) forced expiratory volume in the first second of expiration (FEV1) Integrative fecal and serum metabolome analysis of 92 children with moderate-to-severe asthma (median age: 11.5 years, 34% female) revealed three metabotypes. Metabotype1 had the lowest percentage of allergic rhinitis, with elevated serum ceramides and triglycerides. Metabotype2 had higher odds of asthma control, the highest percentage of children with ≥4 months of breastfeeding, reduced sugar intake, lowest levels of blood neutrophils and serum inflammatory markers, and with elevated serum acylcarnitines and ω-3 fatty acids. Metabotype3 included the highest percentage of uncontrolled asthma patients, with decreased serum cholesteryl esters, phosphatidylcholines, and sphingomyelins, elevated fecal amino acids, and reduced fecal microbiota diversity.
CONCLUSION: Metabotypes in children with moderate-to-severe asthma are linked to asthma control, distinct fecal microbiota and systemic inflammatory patterns. The findings suggest that metabotyping can be valuable in precision medicine approaches for asthma.
背景：儿童哮喘与不同的代谢组学特征有关。
目的：通过粪便和血清代谢组综合分析，确定中重度哮喘儿童的表型（代谢型）。
方法：从全球哮喘治疗倡议≥3级的未控制儿童哮喘队列的系统药理学方法项目中招募儿童。哮喘控制通过哮喘控制测试和年度急性发作史定义。使用液相色谱和流动注射电喷雾电离三重四极杆质谱对粪便和血清进行靶向代谢组学分析。相似性网络融合整合了粪便和血清代谢组谱，然后进行光谱聚类。对聚类进行了哮喘特征、食物日记、粪便微生物群组成以及血清炎症标志物和血细胞水平的差异分析。
结果：对92名中重度哮喘儿童（中位年龄：11.5岁，34%为女性）的粪便和血清代谢组综合分析揭示了三种代谢型。代谢型1的变应性鼻炎发病率最低，血清神经酰胺和甘油三酯升高。代谢型2具有更高的哮喘控制几率，母乳喂养≥4个月的儿童比例最高，糖摄入量减少，血液中性粒细胞和血清炎症标志物水平最低，血清酰基肉碱和ω-3脂肪酸水平升高。代谢型3包括最高比例的未控制哮喘患者，血清胆固醇酯、磷脂酰胆碱和鞘磷脂降低，粪便氨基酸升高，粪便微生物群多样性降低。
结论：中重度哮喘儿童的代谢型与哮喘控制、不同的粪便微生物群和全身炎症模式有关。研究结果表明，代谢分型在哮喘的精准医学方法中具有重要价值。
（中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校）
（J Allergy Clin Immunol. 2025 Apr 23:S0091-6749(25)00457-9. doi: 10.1016/j.jaci.2025.04.017.）
Metabotypes are linked to uncontrolled childhood asthma, gut microbiota, and systemic inflammation.
Abdel-Aziz MI, Hashimoto S, Neerincx AH, Haarman EG, Cecil A, Lintelmann J, Witting M, Hauck SM, Kerssemakers N, Verster JC, Bang C, Franke A, Dierdorp BS, Dekker T, Metwally NKA, Duitman JW, Lutter R, Gorenjak M, Toncheva AA, Kheiroddin P, Harner S, Brandstetter S, Wolff C, Corcuera-Elosegui P, López-Fernández L, Perez-Garcia J, Almeida MM, Sardón-Prado O, Pino-Yanes M, Potočnik U, Kabesch M, Vijverberg SJH, Kraneveld AD, Maitland-van der Zee AH; SysPharmPediA consortium.
Abstract
BACKGROUND:Childhood asthma has been linked to distinct metabolomic profiles.
OBJECTIVES:To identify phenotypes (metabotypes) in children with moderate-to-severe asthma through integrative fecal and serum metabolome analysis.
METHODS:Children from the Systems Pharmacology Approach to Uncontrolled Pediatric Asthma cohort with Global Initiative for Asthma treatment step ≥3 were recruited. Asthma control was defined by the Asthma Control Test and annual exacerbation history. Targeted metabolomics profiling of feces and serum was performed using liquid chromatography and flow injection electrospray ionization-triple quadrupole mass spectrometry. Similarity Network Fusion integrated fecal and serum metabolome profiles, followed by spectral clustering. Clusters were analyzed for differences in asthma characteristics, food diaries, fecal microbiota composition, and levels of serum inflammatory markers and blood cells.
RESULTS:Prebronchodilator (trough) forced expiratory volume in the first second of expiration (FEV1) Integrative fecal and serum metabolome analysis of 92 children with moderate-to-severe asthma (median age: 11.5 years, 34% female) revealed three metabotypes. Metabotype1 had the lowest percentage of allergic rhinitis, with elevated serum ceramides and triglycerides. Metabotype2 had higher odds of asthma control, the highest percentage of children with ≥4 months of breastfeeding, reduced sugar intake, lowest levels of blood neutrophils and serum inflammatory markers, and with elevated serum acylcarnitines and ω-3 fatty acids. Metabotype3 included the highest percentage of uncontrolled asthma patients, with decreased serum cholesteryl esters, phosphatidylcholines, and sphingomyelins, elevated fecal amino acids, and reduced fecal microbiota diversity.
CONCLUSION: Metabotypes in children with moderate-to-severe asthma are linked to asthma control, distinct fecal microbiota and systemic inflammatory patterns. The findings suggest that metabotyping can be valuable in precision medicine approaches for asthma.
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