Comprehensive Profiling of Dietary Responses Through Metabolomics

Abstract

Future health care needs are likely to be dominated by the closely aligned health burdens of an ageing population and non-communicable diseases (NCDs). Whilst ageing presents its own health challenges, ageing is also a key positive risk factor for the major NCDs, type 2 diabetes (T2DM) and cardiovascular disease (CVD). Much of the current understanding of the metabolic changes and dysregulation that accompanies ageing and the development of NCDs are determined by limited blood biochemical measurements, often in fasting conditions. Such measures provide little information of the dynamic metabolic dysregulation that occurs over the day, nor do these measures provide insight into the underlying complexity of the metabolic changes central to the loss of health and onset of serious disease. Metabolomics technologies, including mass spectrometry, enables large-scale and comprehensive analysis of the complex changes in the metabolome. This systems biological approach presents an instantaneous snapshot of the physiological status of an individual’s molecular phenotype, as it encompasses the dynamic integrated response of genes and environment. Importantly, metabolomics analysis can be used to study physiological changes in response to dietary interventions. This thesis presents data from both untargeted metabolomics and lipidomic mass spectrometry approaches to extensively profile both the responsiveness to dietary modification and single meals. Thus, this thesis aimed to comprehensively characterise the metabolic profiles of elderly individuals in response to nutritional interventions. This will present an opportunity for current nutritional recommendations to be evaluated for aging individuals on a molecular level. Furthermore, the postprandial analysis of high-risk individuals known as metabolic syndrome (MetS) will provide insight into the biological disruptions in metabolism.