Plasma metabolomics in adults with cystic fibrosis during a pulmonary exacerbation: A pilot randomized study of high-dose vitamin D3 administration
Plasma metabolomics in adults with cystic fibrosis during a pulmonary exacerbation: A pilot randomized study of high-dose vitamin D3 administration
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DOI：
10.1016/j.metabol.2017.02.006
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发表时间：
2017-05-01
影响因子：
9.8
通讯作者：
Ziegler, Thomas R.
中科院分区：
文献类型：
--
作者：
Alvarez, Jessica A.;Chong, Elizabeth Y.;Ziegler, Thomas R.
背景。囊性纤维化（CF）是一种慢性分解代谢疾病，通常需要住院治疗急性发作的肺恶化。有限的数据表明维生素D可能有有益的临床影响，但维生素D对这种情况下全身代谢的影响尚不清楚。我们使用高分辨率代谢组学（HRM）来评估基线维生素D状态和高剂量维生素D-3给药对CF合并急性肺恶化的成人全身代谢的影响。25名CF住院成人患者参加了一项高剂量维生素D-3 （250,000 IU维生素D-3丸）与安慰剂的随机试验。年龄匹配的健康受试者作为基线比较的参照组。血浆用液相色谱/超高分辨率质谱分析。利用最近的HRM生物信息学和代谢途径富集方法，我们研究了基线维生素D状态（每血清25-羟基维生素D浓度充足与缺乏）和补充维生素D-3后7天的反应之间的关系。一些氨基酸和脂质代谢物在CF和健康对照组之间存在差异，表明整体分解代谢状态。在CF受试者中，有343种代谢物与基线维生素D水平存在差异（P < 0.05），并在脂肪酸、氨基酸和碳水化合物代谢等7种代谢途径中富集。随着时间的推移，维生素D-3和安慰剂治疗的CF受试者共有316种代谢物，其中15种代谢途径（主要代表氨基酸途径）富集（P < 0.05）。在安慰剂组，几种三羧酸循环中间体增加，而几种氨基酸相关代谢物减少；相比之下，这些代谢物在维生素D-3治疗后几乎没有变化。在经历肺恶化的CF成人患者中，HRM检测到的许多代谢途径与维生素D状态和高剂量维生素D-3补充有关。总的来说，这些初步数据表明，在这种临床环境中，高剂量维生素D-3具有抗分解代谢作用。(C) 2017爱思唯尔公司版权所有。
Background. Cystic fibrosis (CF) is a chronic catabolic disease often requiring hospitalization for acute episodes of worsening pulmonary exacerbations. Limited data suggest that vitamin D may have beneficial clinical affects, but the impact of vitamin D on systemic metabolism in this setting is unknown.Objective. We used high-resolution metabolomics (HRM) to assess the impact of baseline vitamin D status and high-dose vitamin D-3 administration on systemic metabolism in adults with CF with an acute pulmonary exacerbation.Design. Twenty-five hospitalized adults with CF were enrolled in a randomized trial of high-dose vitamin D-3 (250,000 IU vitamin D-3 bolus) versus placebo. Age-matched healthy subjects served as a reference group for baseline comparisons. Plasma was analyzed with liquid chromatography/ultra-high resolution mass spectrometry. Using recent HRM bioinformatics and metabolic pathway enrichment methods, we examined associations with baseline vitamin D status (sufficient vs. deficient per serum 25-hydroxyvitamin D concentrations) and the 7-day response to vitamin D-3 supplementation.Results. Several amino acids and lipid metabolites differed between CF and healthy control subjects, indicative of an overall catabolic state. In CF subjects, 343 metabolites differed (P < 0.05) by baseline vitamin D status and were enriched within 7 metabolic pathways including fatty acid, amino acid, and carbohydrate metabolism. A total of 316 metabolites, which showed enrichment for 15 metabolic pathways-predominantly representing amino acid pathways-differed between the vitamin D-3- and placebo-treated CF subjects over time (P < 0.05). In the placebo group, several tricarboxylic acid cycle intermediates increased while several amino acid-related metabolites decreased; in contrast, little change in these metabolites occurred with vitamin D-3 treatment.Conclusions. Numerous metabolic pathways detected by HRM varied in association with vitamin D status and high-dose vitamin D-3 supplementation in adults with CF experiencing a pulmonary exacerbation. Overall, these pilot data suggest an anti-catabolic effect of high dose vitamin D-3 in this clinical setting. (C) 2017 Elsevier Inc. All rights reserved.