Developing a relevant small intestine organ on chip model to study gut microbiome host-interactions

It is now widely recognized that the human microbiome is a central focus in medicine and plays a key role in human disease. The gut microbiome helps maintain health by modulating immune responses, metabolizing nutrients, and influencing disease risk. Disruptions at the microbiome and the host interface have been linked to a wide range of disorders, from metabolic and inflammatory diseases to altered drug efficacy and toxicity. In this context, our work focuses on the microbiome of the small intestine. This intestinal region is responsible for digestion, absorption of metabolites and drugs and harbors its own microbiome, which exhibits a distinct composition and functional profile compared to that of the colon, owing to different environmental conditions. In line with the 2025 directives from the FDA emphasizing the urgent development of organ-on-chip platforms [1], there is a clear need for a reliable in vitro system that can model and sustain complex populations of human aerobic and anaerobic microbiota in contact with living human tissues for better elucidate drugs action on microbiome. We have established a reliable and representative microbial community of healthy proximal small intestine characterized at both taxonomic and functional levels. Our model aims to reproduce a more physiological proximal small intestine system by combining Caco-2 and HT29 epithelial cells with endothelial and immune cells, in order to better unravel gut complexity and enabling a more accurate investigation of host–microbe interactions and microbial responses to pharmacological compounds.

PhD start: 01/01/2026