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Direct Implementation of Intestinal Permeability Test in NMR Metabolomics for Simultaneous Biomarker Discovery—A Feasibility Study in a Preterm Piglet Model

机译:在同时进行生物标志物发现的NMR代谢组学中直接执行肠渗透性测试-在早产仔猪模型中的可行性研究

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摘要

Measurement of intestinal permeability (IP) is often used in the examination of inflammatory gastrointestinal disorders. IP can be assessed by measurement of urinary recovery of ingested non-metabolizable lactulose (L) and mannitol (M). The present study aimed to examine how measurements of IP can be integrated in a NMR-based metabolomics approach for a simultaneous quantification of L/M ratio and biomarker exploration. For this purpose, plasma and urine samples were collected from five-day-old preterm piglets ( = 20) with gastrointestinal disorders (subjected to intra-amniotic lipopolysaccharide (LPS, 1 mg/fetus)) after they had been administrated a 5% lactulose and 5% mannitol solution (15 mL/kg). The collected plasma and urine samples were analyzed by H NMR-based metabolomics. Urine L/M ratio measured by H NMR spectroscopy showed high correlation with the standard measurement of the urinary recoveries by enzymatic assays ( = 0.93, < 0.05). Partial least squares (PLS) regressions and correlation analyses between L/M ratio and NMR metabolomics data revealed that L/M ratio was positively correlated with plasma lactate, acetate and succinate levels and negatively correlated with urinary hippuric acid and glycine. In conclusion, the present study demonstrated that NMR metabolomics enables simultaneous IP testing and discovery of biomarkers associated with an impaired intestinal permeability.
机译:肠通透性(IP)的测量通常用于检查炎症性胃肠道疾病。可以通过测量摄入的非代谢乳果糖(L)和甘露醇(M)的尿回收率来评估IP。本研究旨在研究如何将IP的测量结果整合到基于NMR的代谢组学方法中,以同时定量L / M比和生物标记物的探索。为了这个目的,在给予5%乳果糖后,从五天大的有胃肠道疾病(=羊水内脂多糖(LPS,1mg /胎儿)的早产仔猪(= 20)中收集血浆和尿液样本。和5%甘露醇溶液(15 mL / kg)。通过基于1 H NMR的代谢组学分析收集的血浆和尿液样品。通过1 H NMR光谱测量的尿液L / M比与通过酶法测定尿回收率的标准测量值具有高度相关性(= 0.93,<0.05)。 L / M比与NMR代谢组学数据之间的偏最小二乘(PLS)回归和相关分析表明,L / M比与血浆乳酸,乙酸盐和琥珀酸水平呈正相关,与尿马尿酸和甘氨酸呈负相关。总之,本研究表明,NMR代谢组学能够同时进行IP测试和发现与肠通透性受损相关的生物标志物。

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