In the conventional culture systems in vitro, the challenging organoid approach have recently been overcome by the development of microfluidic Organ Chip models of human intestine. The potential future applications of Intestine-on-Chips in disease modelling, drug development and personalized medicine are leading research to identify and investigate limitations of modern chip-based systems and to focus the attention on the gut epithelium and its specific barrier function playing a significant role in many human disorders and diseases. In this paper, we propose and discuss the importance to implement a multi-parameter analysis on an engineered platform for developing an Epithelial Gut On Chip model.