Serum Metabolomics Indicate Altered Cellular Energy Metabolism in Children With Cystic Fibrosis
Serum Metabolomics Indicate Altered Cellular Energy Metabolism in Children With Cystic Fibrosis
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DOI：
10.1002/ppul.22859
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发表时间：
2014-05-01
影响因子：
3.1
通讯作者：
Muhlebach, Marianne S.
中科院分区：
文献类型：
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作者：
Joseloff, Elizabeth;Sha, Wei;Muhlebach, Marianne S.
研究背景囊性纤维化（Cystic fibrosis，CF）是一种累及呼吸系统以外多器官、多细胞的多系统疾病。代谢组学分析允许同时检测源自细胞，器官，或外源性来源，可能是有价值的疾病严重程度的监测或在diagnosis.AimWe假设，代谢组学使用血清从儿童将区分CF从非CF肺病科目，并将提供洞察CF代谢。31名年龄和性别匹配的患有其他肺部疾病的儿童被用于通过气相色谱和液相色谱进行代谢组学分析。采用偏最小二乘判别分析（PLS-DA）和线性modeling.ResultsA两组之间的代谢物的相对浓度进行了比较，在PLS-DA.线性模型中发现，在459个检测到的代谢物92之间CF和non-CF不同。这些包括脂质代谢中已知的生化物质、氧化剂和与胆汁酸加工异常一致的标志物。细菌代谢物被鉴定，并且在组之间不同，表明CF中的肠道生态失调。作为一个新的发现，几种途径在CF中明显不同，共同指向脂肪酸氧化活性降低。这些途径包括低酮体，低中链肉毒碱，升高的二羧酸和减少2-羟基丁酸从CF的氨基酸代谢相比，非CF。ConclusionSerum代谢组学区别CF从非CF和显示改变细胞能量代谢CF可能反映线粒体功能障碍。未来的研究表明，检查它们与潜在的CF缺陷的关系，以及它们在CFTR修饰药物时代作为疾病严重程度或囊性纤维化跨膜调节因子（CFTR）功能的生物标志物的用途。小儿肺醇。2014; 49：463-472. (c)2013 Wiley Periodicals，Inc.
BackgroundCystic fibrosis (CF) is a multi-system disease affecting multiple organs and cells besides the respiratory system. Metabolomic profiling allows simultaneous detection of biochemicals originating from cells, organs, or exogenous origin that may be valuable for monitoring of disease severity or in diagnosis.AimWe hypothesized that metabolomics using serum from children would differentiate CF from non-CF lung disease subjects and would provide insight into metabolism in CF.MethodsSerum collected from children with CF (n=31) and 31 age and gender matched children with other lung diseases was used for metabolomic profiling by gas- and liquid-chromatography. Relative concentration of metabolites was compared between the groups using partial least square discriminant analyses (PLS-DA) and linear modeling.ResultsA clear separation of the two groups was seen in PLS-DA. Linear model found that among the 459 detected metabolites 92 differed between CF and non-CF. These included known biochemicals in lipid metabolism, oxidants, and markers consistent with abnormalities in bile acid processing. Bacterial metabolites were identified and differed between the groups indicating intestinal dysbiosis in CF. As a novel finding several pathways were markedly different in CF, which jointly point towards decreased activity in the -oxidation of fatty acids. These pathways include low ketone bodies, low medium chain carnitines, elevated di-carboxylic acids and decreased 2-hydroxybutyrate from amino acid metabolism in CF compared to non-CF.ConclusionSerum metabolomics discriminated CF from non-CF and show altered cellular energy metabolism in CF potentially reflecting mitochondrial dysfunction. Future studies are indicated to examine their relation to the underlying CF defect and their use as biomarkers for disease severity or for cystic fibrosis transmembrane regulator (CFTR) function in an era of CFTR modifying drugs. Pediatr Pulmonol. 2014; 49:463-472. (c) 2013 Wiley Periodicals, Inc.