SEMINAR
Centre for Human Metabolomics, North-West University, South Africa
Metabolite profiles relate to the interaction of the genotype with the environment and therefore provide a molecular reflection of the phenotype. Phenotyping is crucial to find biomarkers and obtain biological insights into health and disease in humans. There is a growing recognition that insights into phenotype dynamics, like on homeostasis and allostasis, deepen these insights. Both these phenomena relates to the ability to adapt and cope with a stress challenge. It is furthermore increasingly recognized that cell-intrinsic alterations in nutrient and energy metabolism underlie multiple disease states like cancer, diabetes, and neurological disorders. Using a metabolomics approach, we have recently shown that this also holds true for infants and small children suffering from tuberculosis meningitis (TBM), from which we postulated an astrocyte-microglia lactate shuttle (AMLS) to be operative in TBM. Here we present an overview of (1) central characteristics and requirements for metabolomics investigations (2) illustrative examples of strategies for the analysis of the metabolite profile of patients suffering from an inherited metabolomics disease (e.g. isovaleric acidemia), exposed to an infectious condition (neonates born from HIV+-ART mothers) and patients suspected of having an affect disorder (e.g. fibromyalgia) and finally (3) the AMLS. We are convinced that understanding the dynamics of systemic changes (maintenance of homeostasis, development of allostasis and of an allostatic load) will become crucial in personalized medicine to inform on the underlying biological and pathophysiological processes that characterize well-defined clinical conditions related to metabolism as well as in other multiple metabolic conditions.
Host: Prof. Luc Pellerin