1H Nuclear Magnetic Resonance Metabolomics Analysis Identifies Novel Urinary Biomarkers for Lung Function
1H Nuclear Magnetic Resonance Metabolomics Analysis Identifies Novel Urinary Biomarkers for Lung Function
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DOI：
10.1021/pr1000048
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发表时间：
2010-06-01
影响因子：
4.4
通讯作者：
van den Oord, Edwin J. C. G.
中科院分区：
文献类型：
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作者：
McClay, Joseph L.;Adkins, Daniel E.;van den Oord, Edwin J. C. G.
慢性阻塞性肺疾病（COPD），其特征是慢性气流限制，是一个严重的公共卫生问题。在这项研究中，我们使用质子核磁共振（H-1 NMR）光谱来识别和量化与COPD肺功能相关的代谢物。从197名患有CORD的成年人和195名没有CORD的成年人中收集血浆和尿液。使用600 MHz NMR光谱仪分析样品，并根据肺功能的定量肺活量测定法分析所得光谱。在校正错误发现并调整协变量（性别、年龄、吸烟）后，发现尿液中的几个光谱区域与基线肺功能显著相关。这些区域对应于代谢物胡芦巴碱、马尿酸盐和甲酸盐。每种代谢物的浓度，标准化为尿肌酐，与基线肺功能相关（胡卢巴碱的最小p值= 0.0002）。未发现与血浆代谢物的显著相关性。尿马尿酸盐和甲酸盐通常与肠道微生物菌群有关。这可能表明微生物组在具有不同肺功能的个体之间存在差异。或者，相关的代谢物可能反映了影响整体健康的生活方式差异。我们的研究结果将需要复制和验证，但证明了NMR代谢组学作为筛选工具，用于识别肺部结果的新生物标志物的实用性。
Chronic obstructive pulmonary disease (COPD), characterized by chronic airflow limitation, is a serious public health concern. In this study, we used proton nuclear magnetic resonance (H-1 NMR) spectroscopy to identify and quantify metabolites associated with lung function in COPD. Plasma and urine were collected from 197 adults with CORD and from 195 without CORD. Samples were assayed using a 600 MHz NMR spectrometer, and the resulting spectra were analyzed against quantitative spirometric measures of lung function. After correcting for false discoveries and adjusting for covariates (sex, age, smoking) several spectral regions in urine were found to be significantly associated with baseline lung function. These regions correspond to the metabolites trigonelline, hippurate and formate. Concentrations of each metabolite, standardized to urinary creatinine, were associated with baseline lung function (minimum p-value = 0.0002 for trigonelline). No significant associations were found with plasma metabolites. Urinary hippurate and formate are often related to gut microflora. This could suggest that the microbiome varies between individuals with different lung function. Alternatively, the associated metabolites may reflect lifestyle differences affecting overall health. Our results will require replication and validation, but demonstrate the utility of NMR metabolomics as a screening tool for identifying novel biomarkers of pulmonary outcomes.