Up to now, most studies, investigating the human gut microbiome, focused on the colon ecology, with less attention given to the small intestinal microbiota, partly due to sampling restriction. Nevertheless, the small intestinal microbiota play a crucial role in providing numerous metabolic functions and, overall participating in health. In this project, an in vitro Simulator of the Human Microbial Ecology (SHIME) will be optimized and validated against in vivo samples to recapitulate the composition and functionality of proximal small intestinal microbiota. At first, the normal dynamics due to diet will be investigated. Then, drivers of disease susceptibility will be simulated in the SHIME model to capture the microbial dynamics in specific disease states. Overall, this project will expand our current understanding on composition, dynamics and functionality of the proximal small intestinal microbiota, in health and disease condition.