Gastrointestinal digestion of dietary advanced glycation endproducts using an in vitro model of the gastrointestinal tract (TIM-1).

Protein- and sugar-rich food products processed at high temperatures contain large amounts of dietary advanced glycation endproducts (dAGEs). Our earlier studies have shown that specifically protein-bound dAGEs induce a pro-inflammatory reaction in human macrophage-like cells. To what extent these protein-bound dAGEs survive the human gastrointestinal (GI) tract is still unclear. In this study we analysed gastric and small intestinal digestion of dAGEs using the validated, standardised TNO in vitro gastroIntestinal digestion model (TIM-1), a dynamic in vitro model which mimics the upper human GI tract. This model takes multiple parameters into account, such as: dynamic pH curves, peristaltic mixing, addition of bile and pancreatic digestive enzymes, and passive absorption. Samples of different digested food products were collected at different time points after (i) only gastric digestion and (ii) after both gastric plus small intestinal digestion. Samples were analysed for dAGEs using UPLC-MS/MS for the lysine derived Ne-carboxymethyllysine (CML) and Ne-carboxyethyllysine (CEL), and the arginine derived methylglyoxal-derived hydroimidazolone-1 (MG-H1), and glyoxal-derived hydroimidazolone-1 (G-H1). All AGEs were quantified in their protein-bound and free form. The results of this in vitro study show that protein-bound dAGEs survive gastrointestinal digestion and are additionally formed during small intestinal digestion. In ginger biscuits, the presence MG-H1 in the GI tract increased with more than 400%. This also indicates that dAGEs enter the human GI tract with potential pro-inflammatory characteristics.