Intestinal Absorption and Metabolism of the Tomato Imidazole Alkaloids N-Caprylhistamine-β-glucoside and N-Caprylhistamine.

Histamine-based imidazole alkaloids N-caprylhistamine (HmC8) and N-caprylhistamine-β-glucoside (HmC8-Glc) were recently identified as precursors for a tomato biomarker. As studies regarding metabolism and bioavailability are scarce, the present study aimed at the elucidation of intestinal absorption and metabolism using the Caco-2 model and the pig cecum model to mimic human intestinal conditions. The most abundant imidazole alkaloid HmC8-Glc was neither absorbed nor transferred across cellular barriers but extensively metabolized to HmC8 in the pig cecum model, whereas the aglycon HmC8 is subjected to transport and metabolic processes through the Caco-2 monolayer and metabolized to the bioactive neurotransmitter histamine by the intestinal microbiota. Deduced from the combined results of both methods, HmC8-Glc is not absorbed directly via the intestinal epithelium but requires a metabolic cleavage of the glycosidic bond by the gut microbiota. Because of the high bioavailability of the released HmC8 and histamine, HmC8 and its glucoside might also be involved in the intolerance to tomato products by histamine-intolerant consumers.