Metabolomics profiling of tobacco exposure in children with cystic fibrosis.
Metabolomics profiling of tobacco exposure in children with cystic fibrosis.
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囊性纤维化儿童烟草暴露的代谢组学分析。
DOI：
10.1016/j.jcf.2020.05.003
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Kopp,BenjaminT
中科院分区：
文献类型：
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作者：
Wisniewski,BenjaminL;Shrestha,ChandraL;Zhang,Shuzhong;Thompson,Rohan;Gross,Myron;Groner,JudithA;Uppal,Karan;Ramilo,Octavio;Mejias,Asuncion;Kopp,BenjaminT
背景炎症是儿童CF早期疾病进展的一个组成部分。可改变的环境因素对CF患者感染和炎症的影响知之甚少。我们先前的研究确定，二手烟暴露（SHSe）在CF幼儿中非常普遍。SHSe与炎症增加、细菌负荷增加和临床结局恶化相关。然而，特定的代谢产物和信号通路，调节响应SHSe在CF.MethodsHigh-resolution代谢组学进行了血浆样本从婴儿（n= 25）和儿童（n= 40）CF相比，非CF控制（n= 15）。CF组分层，根据婴儿或儿童年龄和SHSe的status.ResultsGlobal代谢谱分离的年龄和SHSe状态。CF中的SHSe与类固醇生物合成、脂肪酸代谢、半胱氨酸代谢和氧化应激相关途径的变化相关。患有SHSe的CF婴儿表现出对小肠、肝脏和纹状体的代谢物定位改变的富集。患有SHSe的CF儿童表现出与氧化应激相关的器官/组织的代谢物富集，包括线粒体、过氧化物酶体和内质网。在验证性分析中，SHSe与氧化应激和细胞粘附的生物标志物（包括MMP-9、MPO和ICAM-1）的变化相关。结论婴幼儿CF的SHSe与整体代谢组学特征和特定生化途径（包括氧化应激增强）的改变相关。SHSe在早期CF疾病中仍然是一个重要但未充分研究的可变变量。
BackgroundInflammation is integral to early disease progression in children with CF. The effect of modifiable environmental factors on infection and inflammation in persons with CF is poorly understood. Our prior studies determined that secondhand smoke exposure (SHSe) is highly prevalent in young children with CF. SHSe is associated with increased inflammation, heightened bacterial burden, and worsened clinical outcomes. However, the specific metabolite and signaling pathways that regulate responses to SHSe in CF are relatively unknown.MethodsHigh-resolution metabolomics was performed on plasma samples from infants (n= 25) and children (n= 40) with CF compared to non-CF controls (n= 15). CF groups were stratified according to infant or child age and SHSe status.ResultsGlobal metabolomic profiles segregated by age and SHSe status. SHSe in CF was associated with changes in pathways related to steroid biosynthesis, fatty acid metabolism, cysteine metabolism, and oxidative stress. CF infants with SHSe demonstrated enrichment for altered metabolite localization to the small intestine, liver, and striatum. CF children with SHSe demonstrated metabolite enrichment for organs/tissues associated with oxidative stress including mitochondria, peroxisomes, and the endoplasmic reticulum. In a confirmatory analysis, SHSe was associated with changes in biomarkers of oxidative stress and cellular adhesion including MMP-9, MPO, and ICAM-1.ConclusionsSHSe in young children and infants with CF is associated with altered global metabolomics profiles and specific biochemical pathways, including enhanced oxidative stress. SHSe remains an important but understudied modifiable variable in early CF disease.