Untargeted metabolomic profiling identifies disease-specific signatures in food allergy and asthma
Untargeted metabolomic profiling identifies disease-specific signatures in food allergy and asthma
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DOI：
10.1016/j.jaci.2019.10.014
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发表时间：
2020-03-01
影响因子：
14.2
通讯作者：
Chatila, Talal A.
中科院分区：
文献类型：
--
作者：
Crestani, Elena;Harb, Hani;Chatila, Talal A.
背景：食物过敏（FA）影响越来越多的儿童，其原因尚不清楚。新的疾病生物标志物和治愈性治疗方案是非常需要的。目的：我们试图应用非靶向代谢组学分析，以确定FA患者的致病机制和候选疾病生物标志物。方法：基于质谱的非靶向代谢组学分析是在患有单独FA、单独哮喘或FA和哮喘的儿童以及健康儿科对照受试者的血清样本中进行的。结果：在这项初步研究中，与对照组和哮喘患者相比，FA患者表现出疾病特异性代谢组学特征。特别是，FA是唯一与鞘脂水平的显着降低，以及一些其他脂质代谢产物的水平，在面对循环自然杀伤T细胞的正常频率。FA患者和哮喘患者的特异性比较揭示了微生物群敏感的芳香族氨基酸和次级胆汁酸代谢的差异。患有FA和哮喘的儿童表现出与FA单独代谢组学特征一致，但与哮喘无关。在FA的儿童，严重的全身反应的历史和存在的多种FA与色氨酸代谢产物，类花生酸，缩醛磷脂和脂肪酸的水平的变化。结论：FA的儿童有一个疾病特异性的代谢谱，是信息的疾病机制和严重程度，并占主导地位的哮喘的存在。在患有FA的儿童中观察到的较低水平的鞘脂和神经酰胺以及其他代谢组学改变可能反映了肠道中改变的微生物群和免疫细胞亚群之间的相互作用。
Background: Food allergy (FA) affects an increasing proportion of children for reasons that remain obscure. Novel disease biomarkers and curative treatment options are strongly needed.Objective: We sought to apply untargeted metabolomic profiling to identify pathogenic mechanisms and candidate disease biomarkers in patients with FA.Methods: Mass spectrometry-based untargeted metabolomic profiling was performed on serum samples of children with either FA alone, asthma alone, or both FA and asthma, as well as healthy pediatric control subjects.Results: In this pilot study patients with FA exhibited a disease-specific metabolomic signature compared with both control subjects and asthmatic patients. In particular, FA was uniquely associated with a marked decrease in sphingolipid levels, as well as levels of a number of other lipid metabolites, in the face of normal frequencies of circulating natural killer T cells. Specific comparison of patients with FA and asthmatic patients revealed differences in the microbiota-sensitive aromatic amino acid and secondary bile acid metabolism. Children with both FA and asthma exhibited a metabolomic profile that aligned with that of FA alone but not asthma. Among children with FA, the history of severe systemic reactions and the presence of multiple FAs were associated with changes in levels of tryptophan metabolites, eicosanoids, plasmalogens, and fatty acids.Conclusions: Children with FA have a disease-specific metabolomic profile that is informative of disease mechanisms and severity and that dominates in the presence of asthma. Lower levels of sphingolipids and ceramides and other metabolomic alterations observed in children with FA might reflect the interplay between an altered microbiota and immune cell subsets in the gut.