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

Histamine-based imidazole alkaloids N -caprylhistamine (HmC 8 ) and N -caprylhistamine-β-glucoside (HmC 8 -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 HmC 8 -Glc was neither absorbed nor transferred across cellular barriers but extensively metabolized to HmC 8 in the pig cecum model, whereas the aglycon HmC 8 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, HmC 8 -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 HmC 8 and histamine, HmC 8 and its glucoside might also be involved in the intolerance to tomato products by histamine-intolerant consumers.