Bread melanoidins are heterogeneous, nitrogen-containing, brown macromolecules generated during the last stages of the Maillard reaction in bread. The aim of this study was to investigate the impact and fate of these bread melanoidins in the human gastrointestinal tract using in vitro systems. Batch systems as well as the TNO gastrointestinal tract were used for studying the digestion of various bread samples. These samples included bread crumb, bread crust and two bread-crust-simulating models: a fiber-free model (gluten, starch and glucose heated together) and its control, free of Maillard reaction products (gluten heated separately than starch and glucose). Furthermore, the impact of these two bread-crust-simulating models on the gut microbiota was assessed using a static anaerobic batch system. Bread melanoidins from bread crust and its model were shown to be partially digested by amylases and proteases, suggesting that these melanoidins have peptidic as well as glycosidic bonds in their skeleton. The impact of bread melanoidins from the bread-crust-simulating models and their digestion products on the gut microbiota revealed an individual-dependent response for most flora except for enterobacteria. This flora decreased by -22%, -48% & -100% depending on the individual. Thus, bread melanoidins seem to exert an anti-inflammatory effect by inhibiting enterobacteria.