Project description

SIBO is a medical condition characterised by an overgrowth of bacteria in the small intestine. The main objective of the project is to develop an experimental platform for in vitro studies of the influence of individual bacteria on trans-epithelial transport in the small intestine. The in vitro model of the small intestinal mucosa will combine advanced 3D bioprinting approaches with microphysiological systems (MPS). This integration will allow the fabrication of bio-structures with well-defined composition and geometrical properties, and a high degree of control over the culture conditions to mimic the natural physiological environment and steer tissue development in the desired direction. The advantages of the proposed experimental platform over existing in vitro models stem from the specific integration of the 3D bioprinted scaffold and the MPS design, which will align the intestinal epithelium and underlying vascularised tissue within a clear optical pathway. Consequently, this will allow continuous imaging and monitoring of molecular transport from the simulated intestinal lumen through the epithelium and into the vasculature. The project will focus on the transport of metabolites from the luminal to the vascular side of an in vitro epithelium integrated into a microphysiological system (MPS). This model will be exposed to metabolites and cellular material from bacterial species known to cause SIBO. We will compare the profiles of the compounds transferring across the epithelium using untargeted metabolomics based on mass spectrometry. The aim is to identify species-specific indicators with high predictive value for the bacterial pathogen causing SIBO.

Figure 1: General description of the components fulfilling the main objective of the project. In vitro SIM (small intestine mucosa) produced within the MPS using 3D bioprinting and grown under continuous monitoring and close environmental control to study the transport of substances of bacterial origin from the luminal to the vascular circuit.