The gastrointestinal tract (GIT) hosts the most complex microbial community in the human body. Given the extensive metabolic potential which is present in this community, this additional organ is of key importance to maintain a healthy status and several diseases are frequently correlated with an alteration of the composition/functionality of the gut microbiota. Consequently, there is a great interest in identifying potential approaches that could modulate the microbiota and its metabolism to bring about a positive health effect. A classical approach to reach this goal is the use of prebiotics and/or probiotics. How to study the potential effect of new prebiotics/probiotics and how to localize this effect along the full GIT? Human intervention trials are the golden standard to validate functional properties of food products. Yet, most studies on gut microbiota are based on the analysis of fecal samples because they are easily collected in a non-invasive manner. A complementary option is represented by well-designed in vitro simulation technologies. Among all the available systems, the Simulator of Human Intestinal Microbial Ecosystem has already been shown to be a useful model for nutrition studies in terms of analysis of the intestinal microbial community composition and activity. The Simulator of Human Intestinal Microbial Ecosystem is a scientifically validated platform representing the physiology and microbiology of the adult human GIT. Furthermore, recent advances in in vitro modelling also allow to combine the study of bacteria-host interactions, such as mucosal adhesion and interaction with the immune system, thereby further increasing the value of the scientific output.