Towards diagnostic medicine : metabolomic and lipidomic analysis of human capillary blood

Abstract

In the global effort of translating systems biology research into clinical applicability, metabolomics and lipidomics harbor great potential for blood-based medical diagnostics. Gas chromatography mass spectrometry (MS) and direct-infusion electrospray-mass spectrometry are popular platforms for the identification and quantification of metabolites and lipid species in biological samples. By combining a simple, fast, and minimally invasive blood sampling method with these technologies, we are developing an analysis pipeline that allows for both the detailed determination of the current metabolic state as well as metabolic responses to experimental stimuli in vivo in humans. A proof-of-principle study monitored metabolomic changes in the capillary blood of a human volunteer undergoing an exercise regime. In addition to reproducing previous experimental findings, the analysis provided a metabolic mechanism for \u201chitting the wall\u201d, a phenomenon experienced during strenuous exercise. This insight was possible only in light of (1) the frequent sampling facilitated by our sampling strategy, and (2) the identification and quantification of both metabolites that are commonly not analyzed due to technical limitations as well as those that originate in erythrocytes, and can therefore only be systemically interpreted in full blood samples. Furthermore, the lipidomic analysis, which allows for the measurement of free fatty acids, triacylglycerols, and diacylglycerols among others, has indicated that human lipidomic profiles are highly individual and might, aside from representing underlying genetic variation, be strongly influenced by lifestyle and pathological alterations, making the technology ideal for use in preventative and diagnostic medicine. In summary, we have developed a minimally invasive sampling method coupled to a MS-based analysis pipeline that allows for the decoding of human metabolic physiology in health and disease