Changes in urinary metabolomics after meat-containing meals with and without cruciferous or apiaceous vegetables indicate modulation of nucleotide metabolism in addition to xenobiotic metabolism: A randomized crossover study

Colon cancer is a prevalent malignancy influenced by genetics and environmental factors. Diets rich in charred and fried red meats, thus high in heterocyclic aromatic amines [e.g., 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)], are associated with increased colon cancer risk. Conversely, the consumption of fruits and vegetables offers protective effects, potentially modulating multiple carcinogenesis-related pathways. Here, we investigated the metabolomic response to apiaceous and cruciferous vegetable consumption in relation to concomitant PhIP consumption. In a randomized crossover design, 25 participants underwent four phases with four different test meals at the end of each phase. Test meals were well-done hamburger (Control), Control plus cruciferous vegetables (Cru), Control plus apiaceous vegetables (Api), and Control plus combined vegetable types (Cru + Api). Urine samples were subjected to metabolomics analysis using UPLC-MS/MS system. A total of 660 metabolites were identified. The Cru and Api meals showed distinct metabolite profiles, and the Cru + Api meal induced 133 metabolite changes compared to Control. Meals with cruciferous vegetables enriched S-methylcysteine, S-methylcysteine sulfoxide, N-acetylproline, sulforaphane-related compounds, and xenobiotic and amino acid metabolites the most. The Api meal was not as effective in altering xenobiotic metabolites. Api primarily elevated mannitol/sorbitol. To a lesser extent, both vegetable-supplemented meals induced changes in nucleotide-derived metabolites suggesting potential epigenetic modifications. The findings reinforce the influence of these vegetables on xenobiotic metabolism pathways, highlight potential epigenetic mechanisms and potential biomarkers of food intake, and provide further elucidation of their possible roles in colon cancer prevention.