Mogensen Kris M, Lasky-Su Jessica, Rogers Angela J, Baron Rebecca M, Fredenburgh Laura E, Rawn James, Robinson Malcolm K, Massarro Anthony, Choi Augustine M K, Christopher Kenneth B
1 Department of Nutrition, Brigham and Women's Hospital, Boston, Massachusetts, USA.
2 Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
JPEN J Parenter Enteral Nutr. 2017 Feb;41(2):188-197. doi: 10.1177/0148607116656164. Epub 2016 Jul 19.
We hypothesized that metabolic profiles would differ in critically ill patients with malnutrition relative to those without.
We performed a prospective cohort study on 85 adult patients with systemic inflammatory response syndrome or sepsis admitted to a 20-bed medical intensive care unit (ICU) in Boston. We generated metabolomic profiles using gas and liquid chromatography and mass spectroscopy. We followed this by logistic regression and partial least squares discriminant analysis to identify individual metabolites that were significant. We then interrogated the entire metabolomics profile using metabolite set enrichment analysis and network model construction of chemical-protein target interactions to identify groups of metabolites and pathways that were differentiates in patients with and without malnutrition.
Of the cohort, 38% were malnourished at admission to the ICU. Metabolomic profiles differed in critically ill patients with malnutrition relative to those without. Ten metabolites were significantly associated with malnutrition ( P < .05). A parsimonious model of 5 metabolites effectively differentiated patients with malnutrition (AUC = 0.76), including pyroglutamine and hypoxanthine. Using pathway enrichment analysis, we identified a critical role of glutathione and purine metabolism in predicting nutrition. Nutrition status was associated with 28-day mortality, even after adjustment for known phenotypic variables associated with ICU mortality. Importantly, 7 metabolites associated with nutrition status were also associated with 28-day mortality.
Malnutrition is associated with differential metabolic profiles early in critical illness. Common to all of our metabolome analyses, glutathione and purine metabolism, which play principal roles in cellular redox regulation and accelerated tissue adenosine triphosphate degradation, respectively, were significantly altered with malnutrition.
我们假设，与无营养不良的危重症患者相比，有营养不良的危重症患者的代谢谱会有所不同。
我们对85名入住波士顿一家拥有20张床位的医疗重症监护病房（ICU）的患有全身炎症反应综合征或脓毒症的成年患者进行了一项前瞻性队列研究。我们使用气相色谱、液相色谱和质谱法生成代谢组学谱。随后，我们进行逻辑回归和偏最小二乘判别分析，以识别有显著意义的个体代谢物。然后，我们使用代谢物集富集分析以及化学-蛋白质靶点相互作用的网络模型构建来研究整个代谢组学谱，以识别在有和无营养不良的患者中存在差异的代谢物组和途径。
在该队列中，38%的患者在入住ICU时存在营养不良。与无营养不良的危重症患者相比，有营养不良的危重症患者的代谢组学谱有所不同。十种代谢物与营养不良显著相关（P < 0.05）。一个由5种代谢物组成的简约模型能够有效区分营养不良患者（曲线下面积 = 0.76），包括焦谷氨酸和次黄嘌呤。通过通路富集分析，我们确定了谷胱甘肽和嘌呤代谢在预测营养状况方面的关键作用。营养状况与28天死亡率相关，即使在对与ICU死亡率相关的已知表型变量进行调整之后也是如此。重要的是，7种与营养状况相关的代谢物也与28天死亡率相关。
在危重症早期，营养不良与不同的代谢谱相关。在我们所有的代谢组分析中，谷胱甘肽和嘌呤代谢分别在细胞氧化还原调节和加速组织三磷酸腺苷降解中起主要作用，它们均因营养不良而发生了显著改变。
