Fingerprinting the Intestinal Transport of Low-Molecular-Mass Advanced Glycation End-Products (AGEs) Using a Caco-2 Transwell Model

Food-borne advanced glycation end-products could potentially contribute to the endogenous AGE accumulation within the body, albeit to a different extent for different AGEs. This study focuses on characterizing intestinal absorption and intracellular accumulation of 10 selected free low-molecular-mass (LMM) advanced glycation end-products (AGEs) to obtain insight into potential differences in their systemic bioavailability by using a Caco-2 transwell model. The findings reveal that all tested AGEs can cross the intestinal barrier through the paracellular route, albeit to a limited extent. Glycolic acid-lysine-amide (GALA) shows the highest transport percentage, reaching 1.1% ± 0.3% after 2 h, while N-ε-(carboxymethyl)lysine (CML) displays the highest level of accumulation in intestinal cells, reaching 3.5% ± 0.6%. In contrast, cross-linked AGEs appeared to be hardly absorbed or accumulating. Passive transport likely dominates the intestinal uptake of LMM AGEs, with quantitative structure activity relationships based on maximum projection area and molar refractivity or on maximum projection area and molecular mass best describing their uptake rate. This study provides novel insights into differences in bioavailability and intracellular accumulation of LMM AGEs and the potential for fingerprinting their intestinal transport by a new approach methodology.