Using metabolomics to investigate the metabolic signatures and associated pathways linked to short-term exposure to air pollutants

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Human exposure to air pollution contributes to approximately 7 million deaths per year worldwide and owing to the high prevalence of heart disease across the globe, the majority of deaths are attributed to cardiovascular disease (CVD). The epidemiological evidence for independent associations between exposure to poor air quality and CVD mortality is compelling. With respect to illness, heart disease, furring of the arteries (atherosclerosis), heart failure, abnormal heart rhythms and stroke have all been associated with air pollution. For long-term exposure to particulate matter (PM), associated detrimental effects have been shown to persist at concentrations below current annual national standards, whilst reductions in ambient PM (particularly, PM less than 2.5 microns in diameter, PM2.5) have been associated with a slower progression of atherosclerosis.To better understand whether the associations between air pollution and risk of CVD reported in such studies are causal, requires a more comprehensive characterisation of the underlying biochemical pathways and accompanying mechanisms. In particular, if we can identify intermediate steps that lie on the casual pathway(s) linking air pollution to CVD, this could guide appropriate policy and action, including technical solutions and behavioural change, to mitigate the effects of air pollution on health.In this proposal, we aim to use emerging 'whole systems' approaches to study the mechanistic pathways linking ambient air pollution exposure to CVD. These approaches involve metabolic phenotyping technologies (metabolomics) that have emerged as a powerful tool to capture information on a range of toxicological and disease processes. Such metabolic profiling captures a wide range of end products of human metabolism and detects signals from a variety of sources including genetic, dietary, other lifestyle, gut microbial and environmental influences such as air pollutants.Specifically, we will use the concept of the metabolome-wide association study, pioneered by our Centre, to investigate the metabolic fingerprint, which will enable us to discover novel blood-based markers of air pollution exposure (PM2.5 and nitrogen dioxide). Establishing such bio-markers is a key initial step in understanding which biochemical pathways are influenced by air pollution. The results of this research should better our understanding of the mode of action and toxic properties of particulates and gaseous pollutants. Such advances are essential to design and implement better air pollution abatement and control policies, and hence reduce the high burden of air pollution related illness and mortality.