Metabolic derangements identified through untargeted metabolomics in a cross-sectional study of Nigerian children with severe acute malnutrition
Metabolic derangements identified through untargeted metabolomics in a cross-sectional study of Nigerian children with severe acute malnutrition
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DOI：
10.1007/s11306-016-1150-2
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发表时间：
2017-02-01
期刊：
影响因子：
3.6
通讯作者：
Allen, Stephen J.
中科院分区：
文献类型：
--
作者：
McMillan, Amy;Orimadegun, Adebola E.;Allen, Stephen J.
简介 严重急性营养不良 (SAM) 是全世界儿童死亡的主要原因，但 SAM 的发病机制仍知之甚少。最近的研究发现 SAM 儿童的肠道微生物群组成发生了改变，表明微生物在营养不良的发病机制中发挥了作用。 目的 阐明 SAM 的代谢后果以及这些变化是否与肠道微生物群组成的变化相关。 方法 我们应用非靶向多平台代谢组学方法 [气相色谱-质谱 (GC-MS) 和液相色谱-质谱 (LC-MS)] 来分析粪便和血浆样本47 名患有 SAM 的尼日利亚儿童和 11 名对照儿童。通过16S rRNA基因测序评估粪便微生物群的组成。结果血浆代谢组将SAM儿童与对照儿童区分开来，但粪便的微生物或小分子组成没有观察到显着差异。营养不良儿童血浆中 585 个特征的丰度显着改变（Wilcoxon 检验，FDR 校正 P < 0.1），约占代谢组的 15%。与之前的研究一致，患有 SAM 的儿童的氨基酸/二肽和磷脂显着减少，酰基肉碱增加。我们还发现了许多以前未报道过的代谢扰动，包括二糖、截短的纤维蛋白肽、血管紧张素 I、二羟基丁酸、乳酸和血红素的增加，以及属于类二十烷酸和二十二烷酸家族的生物活性脂质的减少。结论我们的研究结果使我们更深入地了解营养不良的代谢后果。需要进一步的研究来确定特定的代谢物是否可以指导改进的治疗，和/或作为评估治疗反应的新型生物标志物。
Introduction Severe acute malnutrition (SAM) is a major cause of child mortality worldwide, however the pathogenesis of SAM remains poorly understood. Recent studies have uncovered an altered gut microbiota composition in children with SAM, suggesting a role for microbes in the pathogenesis of malnutrition.Objectives To elucidate the metabolic consequences of SAM and whether these changes are associated with changes in gut microbiota composition.Methods We applied an untargeted multi-platform metabolomics approach [gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS)] to stool and plasma samples from 47 Nigerian children with SAM and 11 control children. The composition of the stool microbiota was assessed by 16S rRNA gene sequencing.Results The plasma metabolome discriminated children with SAM from controls, while no significant differences were observed in the microbial or small molecule composition of stool. The abundance of 585 features in plasma were significantly altered in malnourished children ( Wilcoxon test, FDR corrected P < 0.1), representing approximately 15% of the metabolome. Consistent with previous studies, children with SAM exhibited a marked reduction in amino acids/dipeptides and phospholipids, and an increase in acylcarnitines. We also identified numerous metabolic perturbations which have not been reported previously, including increased disaccharides, truncated fibrinopeptides, angiotensin I, dihydroxybutyrate, lactate, and heme, and decreased bioactive lipids belonging to the eicosanoid and docosanoid family.Conclusion Our findings provide a deeper understanding of the metabolic consequences of malnutrition. Further research is required to determine if specific metabolites may guide improved management, and/or act as novel biomarkers for assessing response to treatment.