Abstract：
Infants developing necrotizing enterocolitis (NEC) have a different metabolomic profile compared to controls. The potential of specific metabolomics, i.e. amino acids and amino alcohols (AAA), as early diagnostic biomarkers for NEC is largely unexplored. In this multicenter prospective case-control study, longitudinally collected fecal samples from preterm infants (born <30 weeks of gestation) from 1-3 days before diagnosis of severe NEC (Bell\'s stage IIIA/IIIB), were analyzed by targeted high-performance liquid chromatography (HPLC). Control samples were collected from gestational and postnatal age-matched infants. Thirty-one NEC cases (15 NEC IIIA;16 NEC IIIB) with 1:1 matched controls were included. Preclinical samples of infants with NEC were characterized by five increased essential amino acids-isoleucine, leucine, methionine, phenylalanine and valine. Lysine and ethanolamine ratios were lower prior to NEC, compared to control samples. A multivariate model was rendered based on isoleucine, lysine, ethanolamine, tryptophan and ornithine, modestly discriminating cases from controls (AUC 0.67; p < 0.001). Targeted HPLC pointed to several specific AAA alterations in samples collected 1-3 days before NEC onset, compared to controls. Whether this reflects metabolic alterations and has a role in early biomarker development for NEC, has yet to be elucidated.
摘要：
与对照组相比，发生坏死性小肠结肠炎（NEC）的婴儿具有不同的代谢组学特征。特定代谢组学的潜力，即氨基酸和氨基醇（AAA），因为NEC的早期诊断生物标志物大部分尚未开发。在这项多中心前瞻性病例对照研究中，从诊断为严重NEC（Bell’sIIIA/IIIB期）前1-3天纵向收集早产儿（出生<30孕周）的粪便样本，通过靶向高效液相色谱(HPLC)进行分析。从妊娠和出生后年龄匹配的婴儿收集对照样品。包括31例NEC病例（15例NECIIIA；16例NECIIIB），具有1：1匹配的对照。NEC婴儿的临床前样本的特征是五种必需氨基酸-异亮氨酸增加，亮氨酸,蛋氨酸,苯丙氨酸和缬氨酸。在NEC之前，赖氨酸和乙醇胺的比例较低，与对照样品相比。基于异亮氨酸绘制了多变量模型，赖氨酸，乙醇胺,色氨酸和鸟氨酸,适度区分病例与对照组(AUC0.67；p<0.001)。靶向HPLC指出在NEC发病前1-3天收集的样品中有几个特定的AAA改变，与对照组相比。这是否反映了代谢改变，并在NEC的早期生物标志物开发中发挥作用，尚未阐明。
