Invited review: Dairy proteins and bioactive peptides: Modeling digestion and the intestinal barrier

Dairy products are one of the most important sources of biologically active proteins and peptides. The health-promoting functions of these peptides are related to their primary structure, which depends on the parent protein composition. A crucial issue in this field is the demonstration of a cause-effect relationship from the ingested protein form to the bioactive form in vivo. Intervention studies represent the gold standard in nutritional research; however, attention has increasingly been focused on the development of sophisticated in vitro models of digestion to elucidate the mechanism of action of dairy nutrients in a mechanistic way and significantly reduce the number of in vivo trials. On the other hand, the epithelial intestinal barrier is the first gate that actively interacts with digestion metabolites, making the intestinal cells the first target tissue of dairy nutrients and respective metabolites. An evolution of the in vitro digestion approach in the study of dairy proteins and derived bioactive compounds is the setup of combined in vitro digestion and cell culture models taking into consideration the endpoint to measure the target organism (e.g., animal, human) and the key concepts of bioaccessibility, bioavailability, and bioactivity. This review discusses the relevance and challenges of modeling digestion and the intestinal barrier, focusing on the implications for the modeling of dairy protein digestion for bioactivity evaluation.