Institute of Biological Environmental and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA, UK.
Br J Nutr. 2011 Sep;106(6):812-24. doi: 10.1017/S0007114511001164. Epub 2011 May 9.
The lack of robust measures of dietary exposure hinders a quantitative understanding of causal relationships between diet and health. Non-targeted metabolite fingerprinting was used to explore the relationships between citrus exposure in free-living human subjects, estimated by a FFQ, and the chemical content of urine. Volunteers (study 1, n 12; study 2, n 11) were classified into high-, medium- and low-frequency citrus consumption groups. Overnight and spot fasting urine samples were obtained after exposure to a standardised citrus-free evening meal. The urine samples were analysed by flow injection electrospray-ionisation MS followed by supervised multivariate data classification analysis to discover discriminatory features associated with the level of citrus exposure. Good separation of high and low citrus consumption classes was achieved. Deeper exploration of high-ranked explanatory mass signals revealed several correlated signals derived from proline betaine. Targeted analysis of the relative levels of proline betaine in both fasting and overnight urine samples demonstrated good correlation with FFQ exposure data. Acute exposure of volunteers to orange juice resulted in the appearance of proline betaine and several biotransformed products in postprandial urine samples. Biomarker validation showed sensitivities of 80·8-92·2 % and specificities of 74·2-94·1 % (false discovery rate-adjusted P values < 0·05) for elevated proline betaine in participants who reported high citrus consumption. Proline betaine biotransformation products displayed weaker quantitative relationships with habitual citrus exposure. Targeted screening for the presence of biotransformation products of hesperidin and narirutin, known to be abundant in oranges, revealed that they were relatively poor indicators of citrus exposure.
缺乏对饮食暴露的有力衡量标准，阻碍了人们对饮食与健康之间因果关系的定量理解。非靶向代谢物指纹图谱被用于探索自由生活的人体中柑橘暴露与尿液化学物质含量之间的关系，该暴露由 FFQ 估计。志愿者（研究 1，n 12；研究 2，n 11）被分为高、中、低频率柑橘消费组。在暴露于标准化无柑橘晚餐后，获得过夜和即时空腹尿液样本。使用流动注射电喷雾电离 MS 对尿液样本进行分析，然后进行监督多元数据分析，以发现与柑橘暴露水平相关的有区别特征。高和低柑橘消费类别的良好分离得以实现。对高排名解释性质量信号的深入探索揭示了源自脯氨酸甜菜碱的几个相关信号。对空腹和过夜尿液样本中脯氨酸甜菜碱相对水平的靶向分析表明，与 FFQ 暴露数据具有良好的相关性。志愿者急性暴露于橙汁会导致脯氨酸甜菜碱和几种生物转化产物出现在餐后尿液样本中。生物标志物验证显示，在报告高柑橘消费的参与者中，脯氨酸甜菜碱升高的灵敏度为 80.8-92.2%，特异性为 74.2-94.1%（经错误发现率调整的 P 值<0.05）。脯氨酸甜菜碱生物转化产物与习惯性柑橘暴露的定量关系较弱。针对橙皮苷和柚皮苷的生物转化产物的存在进行靶向筛选，已知它们在橙子中含量丰富，但它们是柑橘暴露的相对较差指标。
