## 1 Introduction  
The digestion process can modify the bioactivity of a compound, affecting its bioaccessibility and bioavailability. Therefore, the simulation of the gastrointestinal process is fundamental to predict its potential effect in vivo [1]. To mimic the physiological absorption processes, in vitro digestion models represent very promising approaches as they can be very predictive of in vivo conditions in the study of different food constituents [2, 3]. The static approaches (non-cell-based or cell-based platforms) are widely used to monitor digestibility, bioaccessibility, bioavailability, and bioactivities of different compounds as they can provide fast and cheap results. While they are able to reproduce some digestion conditions, simulating the gastrointestinal fluids (pH values, salt, and enzyme concentrations) and digestive times, they lack mechanical aspects (motility, dynamic circulation, and passive diffusion) and dynamics that cannot provide information concerning biochemical parameters. Another important issue is related to the very wide number of static digestion protocols proposed in the literature, which makes the comparison of results obtained in different laboratories difficult [4, 5, 6]. An international consensus was achieved in the framework of the COST Action InfoGest, which involved more than 40 countries (European countries, USA, Canada, and others) and almost 500 researchers, with a static digestion protocol (COST action InfoGest, 2011-2015). This approach and its advances (InfoGest 2.0, 2019) were projected to set-up an international network working to promote the harmonization of a validated food digestive non-cell-based method consisting of three standardized phases (oral, gastric, and small intestinal duodenum) predicting the in vivo gastrointestinal digestion [7; 8; 9; 10]. Some authors completed this static model by adding the colon step, thus highlighting the importance of colon enzymes and microbial fermentation in the bioavailability and bioactivity of some molecules, as well as in the study of microbiota [11]. Currently, the possibility of an internationally recognized digestion protocol, and the numerous modifications and advancements performed, have also allowed the set-up of models for specific human populations (from infant to elderly) or pathological gastrointestinal conditions [6; 12; 13; 14]. For a more rapid prediction of the intestinal absorption, the digestion set-up can be simplified by using only an intestinal cell-based step, which can also potentially be combined with the abovementioned non-cell-based static approaches to have a more complete digestion process [2; 6]. Over the years, human colon carcinoma cells, such as Caco-2 and HT-29, have been widely used as well-known conventional models to reproduce the intestinal cell transport, uptake, and mucus layer secretion. In fact, they form a monolayer of epithelial cells able to simulate the intestinal structure and functions, ensuring a spontaneous enterocyte-like differentiation and a brush border hydrolytic ability [2; 15; 16; 17]. An important limit of these cell lines is their lower permeability than that registered in in vivo conditions, even if they remain a real promising approach to study molecule absorption. The set-up of dynamic conditions represents an interesting advancement in comparison to static non-cell-based models and static culture systems in the simulation of more simil-physiological conditions. In addition, dynamic models can be promising approaches alternative to animal models, at least in preliminary experiments. However, the important issue related to the complexity of dynamic model validation currently remains unsolved. Over the years, some dynamic models, such as the TNO Gastro-Intestinal Model (TIM), the Human Gastric Simulator (HGS, also called the Riddet model), and the Dynamic Gastric Model (DGM), have been proposed to study gastrointestinal digestion.