Metabotypes are linked to uncontrolled childhood asthma, gut microbiota, and systemic inflammation.

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology Pub Date : 2025-04-23 DOI:10.1016/j.jaci.2025.04.017

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,

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引用次数: 0

Abstract

BACKGROUND Childhood asthma has been linked to distinct metabolomic profiles. OBJECTIVE 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 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. 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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代谢型与不受控制的儿童哮喘、肠道微生物群和全身性炎症有关。

儿童哮喘与不同的代谢组学特征有关。目的通过综合粪便和血清代谢组学分析，确定中重度哮喘患儿的表型（代谢型）。方法从系统药理学方法纳入全球哮喘治疗计划步骤≥3的非受控儿童哮喘队列。哮喘控制通过哮喘控制试验和年度加重史来定义。采用液相色谱和流动注射电喷雾电离-三重四极杆质谱法对粪便和血清进行靶向代谢组学分析。相似网络融合整合粪便和血清代谢谱，然后进行光谱聚类。分析各组哮喘特征、饮食日记、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92例中重度哮喘患儿（中位年龄：11.5岁，女性占34%）的粪便和血清代谢组学综合分析显示出三种代谢类型。代谢型1的变应性鼻炎比例最低，血清神经酰胺和甘油三酯升高。代谢型2具有较高的哮喘控制几率，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。代谢类型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减少。结论：中重度哮喘患儿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是有价值的。

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来源期刊

Journal of Allergy and Clinical Immunology 医学-过敏

CiteScore

25.90

自引率

7.70%

发文量

1302

审稿时长

38 days

期刊介绍： The Journal of Allergy and Clinical Immunology is a prestigious publication that features groundbreaking research in the fields of Allergy, Asthma, and Immunology. This influential journal publishes high-impact research papers that explore various topics, including asthma, food allergy, allergic rhinitis, atopic dermatitis, primary immune deficiencies, occupational and environmental allergy, and other allergic and immunologic diseases. The articles not only report on clinical trials and mechanistic studies but also provide insights into novel therapies, underlying mechanisms, and important discoveries that contribute to our understanding of these diseases. By sharing this valuable information, the journal aims to enhance the diagnosis and management of patients in the future.