摘要
背景：儿童哮喘与独特的代谢组学特征相关。
目的：本研究旨在通过整合粪便和血清代谢组学分析，识别中重度哮喘儿童的代谢表型（metabotypes）。
方法：纳入“儿童未控制哮喘的系统药理学方法”队列中符合全球哮喘防治倡议（GINA）治疗第3级或以上的儿童。通过哮喘控制测试（ACT）和年度急性发作史来定义哮喘控制情况。采用液相色谱和流动注射电喷雾电离-三重四极杆质谱技术，对粪便和血清进行了靶向代谢组学分析。通过相似网络融合整合粪便和血清代谢组学特征，随后进行谱聚类。比较各类簇间哮喘特征、饮食记录、粪便微生物群组成、血清炎症标志物和血细胞水平的差异。
结果：对92名中重度哮喘儿童（中位年龄11.5岁，34%为女性）的整合粪便和血清代谢组学分析鉴定出3种代谢表型。代谢表型1的过敏性鼻炎患病率最低，血清神经酰胺和甘油三酯水平升高。代谢表型2的哮喘控制率更高，母乳喂养≥4个月的儿童占比最高，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，且血清酰基肉碱和ω-3脂肪酸水平升高。代谢表型3中未控制哮喘患者的占比最高，血清胆固醇酯、磷脂酰胆碱和鞘磷脂水平降低，粪便氨基酸水平升高，且粪便微生物群多样性减少。
结论：中重度哮喘儿童的代谢表型与哮喘控制情况、独特的粪便微生物群特征以及全身炎症模式相关。研究结果表明，代谢分型在哮喘精准医学策略中可能具有重要价值。
背景：儿童哮喘与独特的代谢组学特征相关。
目的：本研究旨在通过整合粪便和血清代谢组学分析，识别中重度哮喘儿童的代谢表型（metabotypes）。
方法：纳入“儿童未控制哮喘的系统药理学方法”队列中符合全球哮喘防治倡议（GINA）治疗第3级或以上的儿童。通过哮喘控制测试（ACT）和年度急性发作史来定义哮喘控制情况。采用液相色谱和流动注射电喷雾电离-三重四极杆质谱技术，对粪便和血清进行了靶向代谢组学分析。通过相似网络融合整合粪便和血清代谢组学特征，随后进行谱聚类。比较各类簇间哮喘特征、饮食记录、粪便微生物群组成、血清炎症标志物和血细胞水平的差异。
结果：对92名中重度哮喘儿童（中位年龄11.5岁，34%为女性）的整合粪便和血清代谢组学分析鉴定出3种代谢表型。代谢表型1的过敏性鼻炎患病率最低，血清神经酰胺和甘油三酯水平升高。代谢表型2的哮喘控制率更高，母乳喂养≥4个月的儿童占比最高，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，且血清酰基肉碱和ω-3脂肪酸水平升高。代谢表型3中未控制哮喘患者的占比最高，血清胆固醇酯、磷脂酰胆碱和鞘磷脂水平降低，粪便氨基酸水平升高，且粪便微生物群多样性减少。
结论：中重度哮喘儿童的代谢表型与哮喘控制情况、独特的粪便微生物群特征以及全身炎症模式相关。研究结果表明，代谢分型在哮喘精准医学策略中可能具有重要价值。
（四川大学华西医院呼吸与危重症医学科 邓稞1 王霁1 王刚1 译）
（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
Mahmoud I Abdel-Aziz, Simone Hashimoto, Anne H Neerincx, Eric G Haarman, Alexander Cecil, Jutta Lintelmann, Michael Witting, Stefanie M Hauck, Nikki Kerssemakers, Joris C Verster, Corinna Bang, Andre Franke, Barbara S Dierdorp, Tamara Dekker, Nariman K A Metwally, Jan Willem Duitman, René Lutter, Mario Gorenjak, Antoaneta A Toncheva, Parastoo Kheiroddin, Susanne Harner, Susanne Brandstetter, Christine Wolff, Paula Corcuera-Elosegui, Leyre López-Fernández, Javier Perez-Garcia, Mario Martin-Almeida, Olaia Sardón-Prado, Maria Pino-Yanes, Uroš Potočnik, Michael Kabesch, Susanne J H Vijverberg, Aletta D Kraneveld, Anke H Maitland-van der Zee; SysPharmPediA Consortium
J Allergy Clin Immunol. 2025 Apr 23:S0091-6749(25)00457-9. doi: 10.1016/j.jaci.2025.04.017
BACKGROUND: Childhood asthma has been linked to distinct metabolomic profiles.
OBJECTIVE: We sought 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 or higher were recruited. Asthma control was defined by the Asthma Control Test and annual exacerbation history. Targeted metabolomic 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: Integrative fecal and serum metabolome analysis of 92 children with moderate to severe asthma (median age, 11.5 years, 34% female) revealed 3 metabotypes. Metabotype 1 had the lowest percentage of allergic rhinitis, with elevated serum ceramides and triglycerides. Metabotype 2 had higher odds of asthma control, the highest percentage of children with 4 or more months of breast-feeding, reduced sugar intake, lowest levels of blood neutrophils and serum inflammatory markers, and elevated serum acylcarnitines and ω-3 fatty acids. Metabotype 3 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
CONCLUSIONS: 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.
Mahmoud I Abdel-Aziz, Simone Hashimoto, Anne H Neerincx, Eric G Haarman, Alexander Cecil, Jutta Lintelmann, Michael Witting, Stefanie M Hauck, Nikki Kerssemakers, Joris C Verster, Corinna Bang, Andre Franke, Barbara S Dierdorp, Tamara Dekker, Nariman K A Metwally, Jan Willem Duitman, René Lutter, Mario Gorenjak, Antoaneta A Toncheva, Parastoo Kheiroddin, Susanne Harner, Susanne Brandstetter, Christine Wolff, Paula Corcuera-Elosegui, Leyre López-Fernández, Javier Perez-Garcia, Mario Martin-Almeida, Olaia Sardón-Prado, Maria Pino-Yanes, Uroš Potočnik, Michael Kabesch, Susanne J H Vijverberg, Aletta D Kraneveld, Anke H Maitland-van der Zee; SysPharmPediA Consortium
J Allergy Clin Immunol. 2025 Apr 23:S0091-6749(25)00457-9. doi: 10.1016/j.jaci.2025.04.017
BACKGROUND: Childhood asthma has been linked to distinct metabolomic profiles.
OBJECTIVE: We sought 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 or higher were recruited. Asthma control was defined by the Asthma Control Test and annual exacerbation history. Targeted metabolomic 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: Integrative fecal and serum metabolome analysis of 92 children with moderate to severe asthma (median age, 11.5 years, 34% female) revealed 3 metabotypes. Metabotype 1 had the lowest percentage of allergic rhinitis, with elevated serum ceramides and triglycerides. Metabotype 2 had higher odds of asthma control, the highest percentage of children with 4 or more months of breast-feeding, reduced sugar intake, lowest levels of blood neutrophils and serum inflammatory markers, and elevated serum acylcarnitines and ω-3 fatty acids. Metabotype 3 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
CONCLUSIONS: 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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