{"title":"在HDM和lps诱导的过敏小鼠模型中，外源性补充甜菜碱改善糖皮质激素敏感性和减轻肺部过敏反应","authors":"Qing Wang, Wen He, Yufeng Zhou, Yun Liu, Xiaoling Li, Yingwen Wang, Jiayu Wang, Xiao Han, Xiaobo Zhang","doi":"10.1002/clt2.70039","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Childhood asthma is a heterogeneous disease that exhibits different characteristics and varying severity; however, the metabolite alterations underlying the difference in asthma severity, especially in severe asthma, are not well understood. The aim of this study was to identify the plasma metabolic profile of children with different asthma severity and explore the potential intervention targets in severe asthma and glucocorticoid resistance.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Untargeted liquid chromatography mass spectrometry was utilized to analyze plasma metabolites in 54 children with mild-to-moderate asthma, 50 children with severe asthma and 39 healthy controls. Multivariate statistical analyses were used to explore plasma metabolic alterations that were strongly associated with asthma severity. Meanwhile, the severe allergic airway inflammation mice with glucocorticoid resistance were constructed to validate the potential therapeutic capacity of metabolites.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The plasma metabolic profiles of children with mild to moderate asthma and severe asthma exhibited significant alterations. The distinct plasma metabolite shifts were accompanied by functional alterations in lipid metabolism, particularly choline metabolism, glycerophospholipids and sphingolipid metabolism. 11-cis-retinol, LysoPC (20:4 [8Z,11Z,14Z,17Z]), and glycerophosphatidylcholine were associated with exacerbated airway inflammation and lung function. Furthermore, 2-Hydroxyestradiol, LysoPC (18:3 [6Z,9Z,12Z]), zeaxanthin, and betaine were shifted exclusively in the severe asthma group and may serve as potential biomarkers. Subsequent in vivo studies demonstrated that betaine supplementation partially improved glucocorticoid resistance.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Overall, children with different asthma severity displayed distinct plasma metabolic patterns. These may contribute to the difference in response to glucocorticoids in childhood asthma and could be potential targets and interventions.</p>\n </section>\n </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 2","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70039","citationCount":"0","resultStr":"{\"title\":\"Improvement of glucocorticoid sensitivity and attenuation of pulmonary allergic reactions by exogenous supplementation with betaine in HDM and LPS-induced allergic mouse model\",\"authors\":\"Qing Wang, Wen He, Yufeng Zhou, Yun Liu, Xiaoling Li, Yingwen Wang, Jiayu Wang, Xiao Han, Xiaobo Zhang\",\"doi\":\"10.1002/clt2.70039\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Childhood asthma is a heterogeneous disease that exhibits different characteristics and varying severity; however, the metabolite alterations underlying the difference in asthma severity, especially in severe asthma, are not well understood. The aim of this study was to identify the plasma metabolic profile of children with different asthma severity and explore the potential intervention targets in severe asthma and glucocorticoid resistance.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Untargeted liquid chromatography mass spectrometry was utilized to analyze plasma metabolites in 54 children with mild-to-moderate asthma, 50 children with severe asthma and 39 healthy controls. Multivariate statistical analyses were used to explore plasma metabolic alterations that were strongly associated with asthma severity. Meanwhile, the severe allergic airway inflammation mice with glucocorticoid resistance were constructed to validate the potential therapeutic capacity of metabolites.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>The plasma metabolic profiles of children with mild to moderate asthma and severe asthma exhibited significant alterations. The distinct plasma metabolite shifts were accompanied by functional alterations in lipid metabolism, particularly choline metabolism, glycerophospholipids and sphingolipid metabolism. 11-cis-retinol, LysoPC (20:4 [8Z,11Z,14Z,17Z]), and glycerophosphatidylcholine were associated with exacerbated airway inflammation and lung function. Furthermore, 2-Hydroxyestradiol, LysoPC (18:3 [6Z,9Z,12Z]), zeaxanthin, and betaine were shifted exclusively in the severe asthma group and may serve as potential biomarkers. Subsequent in vivo studies demonstrated that betaine supplementation partially improved glucocorticoid resistance.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>Overall, children with different asthma severity displayed distinct plasma metabolic patterns. These may contribute to the difference in response to glucocorticoids in childhood asthma and could be potential targets and interventions.</p>\\n </section>\\n </div>\",\"PeriodicalId\":10334,\"journal\":{\"name\":\"Clinical and Translational Allergy\",\"volume\":\"15 2\",\"pages\":\"\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2025-02-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70039\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and Translational Allergy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/clt2.70039\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ALLERGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Translational Allergy","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/clt2.70039","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ALLERGY","Score":null,"Total":0}
Improvement of glucocorticoid sensitivity and attenuation of pulmonary allergic reactions by exogenous supplementation with betaine in HDM and LPS-induced allergic mouse model
Background
Childhood asthma is a heterogeneous disease that exhibits different characteristics and varying severity; however, the metabolite alterations underlying the difference in asthma severity, especially in severe asthma, are not well understood. The aim of this study was to identify the plasma metabolic profile of children with different asthma severity and explore the potential intervention targets in severe asthma and glucocorticoid resistance.
Methods
Untargeted liquid chromatography mass spectrometry was utilized to analyze plasma metabolites in 54 children with mild-to-moderate asthma, 50 children with severe asthma and 39 healthy controls. Multivariate statistical analyses were used to explore plasma metabolic alterations that were strongly associated with asthma severity. Meanwhile, the severe allergic airway inflammation mice with glucocorticoid resistance were constructed to validate the potential therapeutic capacity of metabolites.
Results
The plasma metabolic profiles of children with mild to moderate asthma and severe asthma exhibited significant alterations. The distinct plasma metabolite shifts were accompanied by functional alterations in lipid metabolism, particularly choline metabolism, glycerophospholipids and sphingolipid metabolism. 11-cis-retinol, LysoPC (20:4 [8Z,11Z,14Z,17Z]), and glycerophosphatidylcholine were associated with exacerbated airway inflammation and lung function. Furthermore, 2-Hydroxyestradiol, LysoPC (18:3 [6Z,9Z,12Z]), zeaxanthin, and betaine were shifted exclusively in the severe asthma group and may serve as potential biomarkers. Subsequent in vivo studies demonstrated that betaine supplementation partially improved glucocorticoid resistance.
Conclusions
Overall, children with different asthma severity displayed distinct plasma metabolic patterns. These may contribute to the difference in response to glucocorticoids in childhood asthma and could be potential targets and interventions.
期刊介绍：
Clinical and Translational Allergy, one of several journals in the portfolio of the European Academy of Allergy and Clinical Immunology, provides a platform for the dissemination of allergy research and reviews, as well as EAACI position papers, task force reports and guidelines, amongst an international scientific audience.
Clinical and Translational Allergy accepts clinical and translational research in the following areas and other related topics: asthma, rhinitis, rhinosinusitis, drug hypersensitivity, allergic conjunctivitis, allergic skin diseases, atopic eczema, urticaria, angioedema, venom hypersensitivity, anaphylaxis, food allergy, immunotherapy, immune modulators and biologics, animal models of allergic disease, immune mechanisms, or any other topic related to allergic disease.
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