MSACL 2025 Abstract

High-Throughput Metabolomics for Global Health: Insights Into Dietary and Tobacco Smoke Exposures

Zachary Kroezen, Erick Helmeczi, Liam Surry, Philip Britz-Mckibbin
McMaster University, Hamilton, ON, Canada

Philip Britz-Mckibbin, PhD (Presenter) McMaster University

Presenter Bio: Philip Britz-McKibbin is a Professor at the Department of Chemistry and Chemical Biology at McMaster University in Hamilton, Canada. Dr. Britz-McKibbin obtained his BSc in Chemistry (U. Toronto, 1994), and PhD in Analytical Chemistry (UBC, 2000) and a Japan Society for Promotion of Science PDF position in Japan (Hyogo University, 2001-2003) prior to starting his academic position at McMaster. His research group is an affiliate member of The Metabolomics Innovation Centre (TMIC) – Canada’s national metabolomics laboratory. His research interests in bio-analytical chemistry, separation science, mass spectrometry and metabolomics include the design of novel analytical strategies to quantify and identify metabolites of clinical significance in complex biological samples. Philip’s laboratory aims to discover new biomarkers that support early detection and improved therapeutic interventions with emphasis on inherited metabolic disorders and chronic human diseases ranging from cystic fibrosis to inflammatory bowel disease. His research interests include the development of high throughput metabolic screening methods for large-scale epidemiological studies with recent focus on evaluating dietary and tobacco smoke exposures in global populations.

Relevant Financial Disclosures (within past 24 months, reported on May 30, 2025) No relevant financial relationship(s) to disclose.

INTRODUCTION:
A poor quality diet and tobacco smoking are two leading modifiable risk factors in chronic disease burden and premature death globally. However, epidemiological studies often rely on questionnaires to assess dietary habits and lifestyle in large populations that are prone to bias and misreporting.

OBJECTIVES:
The main objective of this work is to validate a new method for non-invasive biomonitoring of urinary biomarkers reflecting habitual diet and tobacco smoke exposures that were compared to self-reports.

METHODS:
Multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS) in conjunction with an automated software for data processing of multiplexed separations offer a high throughput platform for the untargeted analysis of polar/ionic metabolites [1] directly in urine samples. In this study, more than 5000 urine samples from participants in fourteen countries were analyzed by MSI-CE-MS under positive and negative ion mode conditions across three batches of runs with stringent quality control. A targeted analysis of up to seven urinary nicotine metabolites was first developed as a more objective indicator of recent tobacco smoke exposures and nicotine dependence, including biochemical verification of never smokers [2]. A new data workflow was also developed to identify urinary biomarkers of food intake and diet quality, which were correlated to self-reports. Unknown dietary biomarkers in urine were subsequently identified by collision-induced dissociation experiments via MS/MS.

RESULTS:
Herein, we report the urinary total nicotine equivalent and the nicotine metabolic ratio from 5000 participants in 14 different countries, which was critical to verify active smokers from likely secondhand smoke exposures and true non-exposed never smokers. Also, a comprehensive analysis of urinary nicotine metabolites allowed for stratification of fast from slower nicotine metabolizers as required to assess the true hazards from tobacco smoking in diverse populations. Method validation included assessment of the intermediate precision and accuracy of MSI-CE-MS for reliable determination of urinary nicotine metabolites in pooled quality control and certified reference samples. We also validated a panel of selective and robust dietary biomarkers of food intake in urine, including common beverages (e.g., coffee, tea etc.). Further, the distinct dietary patterns of high-risk heavy smokers of tobacco with fast nicotine metabolism was also investigated.

CONCLUSION:
MSI-CE-MS together with an automated software tool for targeted and untargeted metabolite profiling offers a rapid, low-cost and environmental-sound analytical platform for large-scale epidemiological studies. We also validated a panel of urinary biomarkers that can serve as objective indicators of tobacco smoke and dietary exposures. This allows for better calibration or adjustment of self-reported data in support of evidence-based global health policies for chronic disease prevention, such as smoking cessation and a protective diet.

REFERENCES:
1. Sathish, T., et al. Variations in Risks From Smoking Between High-Income, Middle-Income, and Low-Income Countries: An Analysis of Data from 179 000 Participants From 63 Countries. Lancet Global Health, 2022. 10(2): p. e216-e226.
2. Helmeczi, E., et al. A Software Tool for Rapid and Automated Preprocessing of Large-Scale Serum Metabolomic Data by Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry. Anal Chem. 2025. 97(1): p. 175-184.