Metabolome alterations in severe critical illness and vitamin D status
Metabolome alterations in severe critical illness and vitamin D status
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DOI：
10.1186/s13054-017-1794-y
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发表时间：
2017-07-28
期刊：
影响因子：
15.1
通讯作者：
Christopher, Kenneth B.
中科院分区：
文献类型：
--
作者：
Lasky-Su, Jessica;Dahlin, Amber;Christopher, Kenneth B.
背景：危重疾病中代谢稳态受到严重破坏。鉴于维生素 D 的多效性作用，我们假设危重患者之间的代谢特征与其维生素 D 状态有关。方法：我们对 2008 年至 2010 年间在 20 个床位的医疗 ICU 中接受治疗的 65 名患有全身炎症反应综合征或脓毒症的成年人进行了代谢组学研究。为了确定危重病患者中与维生素 D 状态相关的关键代谢物和代谢途径，我们首先生成了使用气相和液相色谱质谱法获得代谢组数据。我们随后通过偏最小二乘判别分析来识别重要的个体代谢物。然后，我们使用代谢物集富集分析来询问整个代谢组学概况，以确定区分维生素 D 状态的代谢物组和途径。最后，我们进行了逻辑回归，构建了一个对维生素 D 状态很重要的化学-蛋白质靶标相互作用的网络模型。结果：服用 25(OH)D 15 ng/ml 的危重患者的代谢组学特征存在显着差异。特别是，1,5-脱水葡萄糖醇、色氨酸甜菜碱和 3-羟基辛酸的增加以及 2-花生四烯酰基甘油磷酸胆碱和 N-6-三甲基赖氨酸的减少是 25(OH) D >15 ng/ml 的强预测因子。这五种代谢物的组合导致区分 25(OH) D >15 ng/ml 的曲线下面积为 0.82 (95% CI 0.71-0.93)。与谷胱甘肽代谢和谷氨酸代谢相关的代谢途径在维生素 D 状态方面显着丰富。结论：维生素 D 状态与危重疾病期间的差异代谢特征相关。谷胱甘肽和谷氨酸途径代谢分别在氧化还原调节和免疫调节中起主要作用，随着维生素 D 状态的变化而显着改变。
Background: Metabolic homeostasis is substantially disrupted in critical illness. Given the pleiotropic effects of vitamin D, we hypothesized that metabolic profiles differ between critically ill patients relative to their vitamin D status.Methods: We performed a metabolomics study on biorepository samples collected from a single academic medical center on 65 adults with systemic inflammatory response syndrome or sepsis treated in a 20-bed medical ICU between 2008 and 2010. To identify key metabolites and metabolic pathways related to vitamin D status in critical illness, we first generated metabolomic data using gas and liquid chromatography mass spectroscopy. We followed this by partial least squares-discriminant analysis to identify individual metabolites that were significant. We then interrogated the entire metabolomics profile using metabolite set enrichment analysis to identify groups of metabolites and pathways that were differentiates of vitamin D status. Finally we performed logistic regression to construct a network model of chemical-protein target interactions important in vitamin D status.Results: Metabolomic profiles significantly differed in critically ill patients with 25(OH)D 15 ng/ml. In particular, increased 1,5-anhydroglucitol, tryptophan betaine, and 3-hydroxyoctanoate as well as decreased 2-arachidonoyl-glycerophosphocholine and N-6-trimethyllysine were strong predictors of 25(OH) D >15 ng/ml. The combination of these five metabolites led to an area under the curve for discrimination for 25(OH) D >15 ng/ml of 0.82 (95% CI 0.71-0.93). The metabolite pathways related to glutathione metabolism and glutamate metabolism are significantly enriched with regard to vitamin D status.Conclusion: Vitamin D status is associated with differential metabolic profiles during critical illness. Glutathione and glutamate pathway metabolism, which play principal roles in redox regulation and immunomodulation, respectively, were significantly altered with vitamin D status.