TARGETED AND NON-TARGETED METABOLITE ANALYSIS FOR DISEASE RISK ASSESSMENT: MEASURING BIOMARKERS OF SMOKE EXPOSURE AND HABITUAL DIET

Abstract

Exposomics applies metabolomics methods and technologies to the comprehensive analysis of all low molecular weight molecules (< 1.5 kDa) in complex biological samples to characterize the interaction between cellular metabolism and exogenous lifestyle exposures that determine health and quality of life. To fully access the diverse classes of biological molecules related to an individual’s metabolic profile, metabolomics frequently requires the use of complementary analytical platforms, and employs targeted and untargeted molecular profiling strategies to identify biomarkers that are clinically relevant to an individual’s health status. Chapter 2 describes a quinoline-based boronic acid biosensor for N-acetylneuraminic acid that undergoes a striking binding enhancement under strongly acidic conditions. For the first time, this work allows for direct analysis of acidic sugars with high selectivity when using UV absorbance or fluorescence detection based on formation of a highly stable boronate ester complex with metabolites containing an α-hydroxycarboxylate moiety. Chapter 3 describes a targeted analysis of 24 different organic contaminants using GC-MS that can serve as biomarkers of recent smoke exposure following search-and-rescue training exercises by firefighters located at three different sites across the province of Ontario. Importantly, skin and possible respiratory uptake of various polycyclic aromatic hydrocarbons, methoxyphenols, and resin acids was confirmed by peak excretion of several wood smoke biomarkers in urine within 6 h following acute exposure. Chapter 4 applied a cross-platform metabolomics strategy based on CE-MS and GC-MS in order to identify and validate dietary biomarkers in matching plasma and urine samples collected from healthy participants in the pilot Diet and Gene Interaction Study (DIGEST). For the first time, we demonstrate that a panel of metabolites can serve as reliable biomarkers following contrasting Prudent and Western diets over 2 weeks of food provisions, which correlated well with self-reported diet records. This work paves the way for the development of objective biomarkers for accurate assessment of wood smoke exposures, as well as complex dietary patterns as required for new advances in occupational health and nutritional epidemiology.