Dietary exposure biomarker-lead discovery based on metabolomics analysis of urine samples

Abstract

Although robust associations between dietary intake and population health are evident from conventional observational epidemiology, the outcomes of large-scale intervention studies testing the causality of those links have often proved inconclusive or have failed to demonstrate causality. This apparent conflict may be due to the well-recognised difficulty in measuring habitual food intake which may lead to confounding in observational epidemiology. Urine biomarkers indicative of exposure to specific foods offer information supplementary to the reliance on dietary intake self-assessment tools, such as FFQ, which are subject to individual bias. Biomarker discovery strategies using non-targeted metabolomics have been used recently to analyse urine from either short-term food intervention studies or from cohort studies in which participants consumed a freely-chosen diet. In the latter, the analysis of diet diary or FFQ information allowed classification of individuals in terms of the frequency of consumption of specific diet constituents. We review these approaches for biomarker discovery and illustrate both with particular reference to two studies carried out by the authors using approaches combining metabolite fingerprinting by MS with supervised multivariate data analysis. In both approaches, urine signals responsible for distinguishing between specific foods were identified and could be related to the chemical composition of the original foods. When using dietary data, both food distinctiveness and consumption frequency influenced whether differential dietary exposure could be discriminated adequately. We conclude that metabolomics methods for fingerprinting or profiling of overnight void urine, in particular, provide a robust strategy for dietary exposure biomarker-lead discovery.

Comparing metabolite profiles of habitual diet in serum and urine

“…Our findings for specific food-metabolite associations replicate $31 associations previously reported from clinical and population studies, including for fruit and juice (13)(14)(15)(48)(49)(50)(51)(52), red meat (13,(53)(54)(55), fish (15,51,56), nuts (15,51), liquor and wine (15,57), coffee (15,16,51,58,59), and multivitamin supplement (15) intake. Our serum findings parallel those reported by the Atherosclerosis Risk in Communities study (n = 1977) (51) and the Prostate, Lung, Colorectal, and Ovarian Cancer screening trial (n = 502) (15) for metabolites associated with citrus (stachydrine, chiro-inositol, scyllo-inositol, and N-methyl proline), coffee (trigonelline, quinate, paraxanthine, 1-methylxanthine, and caffeine), fish (CMPF), nuts (tryptophan betaine), alcohol (ethyl glucuronide) and multivitamins (pyridoxate and pantothenate).…”

“…Metabolomics platforms measure hundreds of identifiable (and up to thousands of currently unidentified) metabolic parent compounds, substrates, and products in biospecimens with the use of mass spectrometry or proton nuclear magnetic resonance (11,12), creating an opportunity to improve dietary assessment by establishing objective biomarkers (13)(14)(15). Metabolites reflect biologically relevant components of food and their metabolic effects, concentrations of which are determined by nutrient availability after food preparation, nutrient interactions, baseline nutrient status, environment, genetics, and the gut microbiome are accounted for (6,16).…”

“…Metabolite profiling has been used in several studies to identify candidate dietary biomarkers and to explore diet-disease mechanisms (13,(15)(16)(17)(18)(19). However, the critical question of which biospecimens typically collected in clinical and epidemiologic studies (i.e., blood or urine) provide metabolite biomarkers that better characterize habitual diet remains unanswered.…”

Twenty years of research in the Human Nutrition Research Centre, Newcastle University, 1994–2014

“…; Beckmann et al . ). Using a metabolomics‐based approach, research by HNRC was the first to identify hydroxylated phenylacetamides as biomarkers of consumption of wholegrain sourdough rye bread in humans (Beckmann et al .…”

Guide and Position of the International Society of Nutrigenetics/Nutrigenomics on Personalized Nutrition: Part 2 - Ethics, Challenges and Endeavors of Precision Nutrition

“…Advances in human metabolic profiling offer improved opportunities for studying food biomarkers and individuals; thanks to such advances, individuals do not always need to be fasting to be studied [131,132]. …”