S-49-1: NUTRITION, CARDIO-METABOLIC RISK AND THE METABOLOME

Abstract

Dietary and nutritional factors are known to be important in the emergence and progression of cardiometabolic disease risk factors including high blood pressure and obesity. At population level, large variations in cardiometabolic and cardiovascular disease risk across populations and temporal variations within populations point to the key importance of lifestyle factors including diet in the occurrence of these diseases. For example, epidemiological studies (including INTERSALT and INTERMAP studies), animal models and randomised controlled clinical trials (including the recent Salt Substitute and Stroke Study (SSaSS) in rural China [1]) have demonstrated the importance of salt intake in raised blood pressure and the rise of blood pressure with age, with interventions to lower salt intake resulting in lower risk of stroke, heart disease and all-cause mortality. The “exposome“ concept has been proposed as a means to encapsulate the effects of environmental and lifestyle exposures (including diet) on the individual’s metabolism and risk of disease. The concept is that these factors interact at a cellular and systems level (against a background of genetic susceptibility) to determine the trajectory of health or disease. Their associated molecular signatures can be captured using omic technologies -- with the measurement of small molecule metabolites in blood or urine (metabolomics) being the most proximal to the phenotype. Metabolomics captures at high-resolution the biological signatures from the totality of internal (biochemical) and external exposures, including nutritional exposures and interactions between diet and the gut microbiome. These represent the end products of metabolic pathways associated with a wide range of physiological and pathophysiological processes, as well as direct signatures of lifestyle exposures including dietary intakes [2]. Agnostic (untargeted) analyses through the metabolome-wide association study (MWAS) applied to large-scale epidemiological data, coupled with targeted measurement of specific metabolites, can reveal novel signatures of perturbations in metabolic and disease pathways associated with nutritional exposures, including those related to blood pressure and adiposity. Development of nutritional biomarkers using such approaches could lead to objective markers of dietary intakes and diet quality which may be important for developing and monitoring dietary goals for long-term health.