Department of Anesthesiology, School of Medicine, University of Colorado Denver, Aurora, Colorado, USA.
Am J Respir Crit Care Med. 2011 Sep 15;184(6):647-55. doi: 10.1164/rccm.201103-0474CI. Epub 2011 Jun 16.
Metabolomics, a science of systems biology, is the global assessment of endogenous metabolites within a biologic system and represents a "snapshot" reading of gene function, enzyme activity, and the physiological landscape. Metabolite detection, either individual or grouped as a metabolomic profile, is usually performed in cells, tissues, or biofluids by either nuclear magnetic resonance spectroscopy or mass spectrometry followed by sophisticated multivariate data analysis. Because loss of metabolic homeostasis is common in critical illness, the metabolome could have many applications, including biomarker and drug target identification. Metabolomics could also significantly advance our understanding of the complex pathophysiology of acute illnesses, such as sepsis and acute lung injury/acute respiratory distress syndrome. Despite this potential, the clinical community is largely unfamiliar with the field of metabolomics, including the methodologies involved, technical challenges, and, most importantly, clinical uses. Although there is evidence of successful preclinical applications, the clinical usefulness and application of metabolomics in critical illness is just beginning to emerge, the advancement of which hinges on linking metabolite data to known and validated clinically relevant indices. In addition, other important aspects, such as patient selection, sample collection, and processing, as well as the needed multivariate data analysis, have to be taken into consideration before this innovative approach to biomarker discovery can become a reliable tool in the intensive care unit. The purpose of this review is to begin to familiarize clinicians with the field of metabolomics and its application for biomarker discovery in critical illnesses such as sepsis.
代谢组学是系统生物学的一个分支，它是对生物系统内内源性代谢物的全面评估，代表了基因功能、酶活性和生理状态的“瞬时”读取。代谢物的检测，无论是单独检测还是作为代谢组学图谱进行分组检测，通常都是通过核磁共振波谱或质谱技术在细胞、组织或生物体液中进行，然后进行复杂的多变量数据分析。由于代谢失衡在危重病中很常见，代谢组学可能有许多应用，包括生物标志物和药物靶点的鉴定。代谢组学还可以显著提高我们对急性疾病（如败血症和急性肺损伤/急性呼吸窘迫综合征）复杂病理生理学的理解。尽管有这种潜力，但临床界对代谢组学领域知之甚少，包括所涉及的方法、技术挑战，以及最重要的临床应用。尽管有成功的临床前应用的证据，但代谢组学在危重病中的临床应用和实用性才刚刚开始显现，其发展取决于将代谢物数据与已知的和经过验证的临床相关指标联系起来。此外，在这种创新的生物标志物发现方法成为重症监护病房的可靠工具之前，还必须考虑其他重要方面，如患者选择、样本采集和处理，以及所需的多变量数据分析。本文的目的是使临床医生开始熟悉代谢组学领域及其在败血症等危重病中生物标志物发现的应用。
