Mealtime, temporal, and daily variability of the human urinary and plasma metabolomes in a tightly controlled environment.
Mealtime, temporal, and daily variability of the human urinary and plasma metabolomes in a tightly controlled environment.
复制标题
DOI：
10.1371/journal.pone.0086223
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Weiss RH
中科院分区：
文献类型：
--
作者：
Kim K;Mall C;Taylor SL;Hitchcock S;Zhang C;Wettersten HI;Jones AD;Chapman A;Weiss RH
虽然代谢组学在诊断生物标记物和治疗靶点发现方面具有巨大的潜力，但由于环境暴露(包括饮食)和人类昼夜节律的影响，其有效性可能会减弱。为了成功地将代谢组学结果转化为临床环境，有必要详尽地定义代谢组变异的来源。为了解决这些问题并测量一天中尿液和血浆代谢物的变异性，我们进行了一项全面的住院研究，我们对26名志愿者(13名没有已知疾病的健康受试者和13名未服用药物的常染色体显性多囊肾病健康受试者)进行了血液和尿液的非靶向代谢组学分析。在三天的时间里，这些人在临床研究机构的两个不同场合接受了评估，同时接受了标准化的、基于体重的饮食。受试者在同一时间段提供餐前和餐后的血和尿样本，所有样本均采用基于快速通道LC-MS的全球代谢组学分析。血液和尿代谢物的最大变异性来源是样品制备和分析等技术问题，较小的变异性是由于生物变量、膳食和一天中的时间。与晚餐相比，早晨之后观察到更高的代谢组变异性，但每天的变异性很小，尿代谢组变异性大于血液。因此，我们认为血液和尿液是代谢组学研究的合适生物流体，尽管仅靠非靶向质谱学可能不能提供足够的精确度来揭示代谢组的细微变化。可能需要额外的目标分析来支持来自非目标质谱分析的数据。根据这些发现，未来的代谢组学研究应该考虑这些变异性的来源，以便进行适当的代谢组学测试和代谢组学数据的可靠临床翻译。
While metabolomics has tremendous potential for diagnostic biomarker and therapeutic target discovery, its utility may be diminished by the variability that occurs due to environmental exposures including diet and the influences of the human circadian rhythm. For successful translation of metabolomics findings into the clinical setting, it is necessary to exhaustively define the sources of metabolome variation. To address these issues and to measure the variability of urinary and plasma metabolomes throughout the day, we have undertaken a comprehensive inpatient study in which we have performed non-targeted metabolomics analysis of blood and urine in 26 volunteers (13 healthy subjects with no known disease and 13 healthy subjects with autosomal dominant polycystic kidney disease not taking medication). These individuals were evaluated in a clinical research facility on two separate occasions, over three days, while on a standardized, weight-based diet. Subjects provided pre- and post-prandial blood and urine samples at the same time of day, and all samples were analyzed by “fast lane” LC-MS-based global metabolomics. The largest source of variability in blood and urine metabolomes was attributable to technical issues such as sample preparation and analysis, and less variability was due to biological variables, meals, and time of day. Higher metabolome variability was observed after the morning as compared to the evening meal, yet day-to-day variability was minimal and urine metabolome variability was greater than that of blood. Thus we suggest that blood and urine are suitable biofluids for metabolomics studies, though nontargeted mass spectrometry alone may not offer sufficient precision to reveal subtle changes in the metabolome. Additional targeted analyses may be needed to support the data from nontargeted mass spectrometric analyses. In light of these findings, future metabolomics studies should consider these sources of variability to allow for appropriate metabolomics testing and reliable clinical translation of metabolomics data.
登录
查看更多内容
HMDB：人类代谢组数据库。
影响因子：
14.9
作者：
Wishart, David S;Tzur, Dan;Knox, Craig;Eisner, Roman;Guo, An Chi;Young, Nelson;Cheng, Dean;Jewell, Kevin;Arndt, David;Sawhney, Summit;Fung, Chris;Nikolai, Lisa;Lewis, Mike;Coutouly, Marie-Aude;Forsythe, Ian;Tang, Peter;Shrivastava, Savita;Jeroncic, Kevin;Stothard, Paul;Amegbey, Godwin;Block, David;Hau, David D;Wagner, James;Miniaci, Jessica;Clements, Melisa;Gebremedhin, Mulu;Guo, Natalie;Zhang, Ying;Duggan, Gavin E;Macinnis, Glen D;Weljie, Alim M;Dowlatabadi, Reza;Bamforth, Fiona;Clive, Derrick;Greiner, Russ;Li, Liang;Marrie, Tom;Sykes, Brian D;Vogel, Hans J;Querengesser, Lori
通讯作者：
Querengesser, Lori
影响因子：
4.4
作者：
Llorach, Rafael;Urpi-Sarda, Mireia;Andres-Lacueva, Cristina
通讯作者：
Andres-Lacueva, Cristina
影响因子：
11.2
作者：
Ganti S;Taylor SL;Abu Aboud O;Yang J;Evans C;Osier MV;Alexander DC;Kim K;Weiss RH
通讯作者：
Weiss RH
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
7
作者：
Kim, Kyoungmi;Aronov, Pavel;Weiss, Robert H.
通讯作者：
Weiss, Robert H.