The human gut microbiome is a key determinant of human health, with extensive research assessing the colonic and fecal microbiomes at different levels. Studies of the small intestinal microbiota are underrepresented in the scientific publications due to the difficulty to sampling this anatomical site. This proposal aims to develop a 3D small intestine ecosystem model resembling the human microbiota and the host interphase at the small intestine, embodying the architecture and microenvironment of native intestine. It will cover the technological gap of mimicking the small intestinal microbial ecosystem into in vitro models. This model will allow the research community and industry sector to evaluate the oral bioavailability of drugs or food compounds and simultaneously assess the microbial, host and environment interactions. The combination of fundamental insights from microbiology, human physiology, cell cultures, material science and reactor technology will be integrated in a multidisciplinary approach to attain as a main deliverable a reproducible model with a broad range of applications. This model will provide quantitative parameters to evaluate functional and structural microbiome shifts and also host parameters (e.g. epithelial barrier function, immune response). The applicability of this system to pharmaceutical and nutrition industry and also for basic research will generate new knowledge and also a highly applicable outcome, both fitting with the BIO4 scope