People can only ingest food through the mouth and oral administration remains the preferred route for the delivery of drugs or dietary supplements. However, any orally ingested compound must first survive digestion and then be absorbed at the small intestine to reach systemic circulation. Failure to predict the amount of orally administrated foods or drugs that reaches the blood using pre-clinical models can lead to the lack of success of new candidates in expensive clinical trials. This entails important consequences for society including i) elevated costs for the development of new drugs, ii) delayed research of new pharmaceutical and food compounds iii) continuous use of animal models, and potentially iv) the introduction of drugs with suboptimal properties.
The overarching goal of the GASTRIC project was to develop and fabricate the first automated microfluidics-based device for complete simulation of the processes of digestion and intestinal absorption of orally ingested bioactive compounds. The device should offer the possibility to study minute sample amounts, with high resolution and with the potential for high-throughput analysis, which is key for its adoption by large pharmaceutical and food industries with high economic and social impact.
As main conclusions, the GASTRIC project resulted in 2 alternative designs that could effectively simulate human intestinal digestion in a miniaturised manner. The second device iteration is fully automated and sensorised with pH and temperature sensors allowing to control both parameters using a closed feedback loop. The output of the Digestion devices could then be studied in another cell-laden device that simulates intestinal absorption under dynamic fluid flow conditions - the GASTRIC Gut Chip, which integrates sensors for real-time TEER monitoring. In addition, primary human colon samples were used to derive intestinal organoids with the aim of integrating these cultures in the Gut Chip to add physiological relevance and potentiate personalised patient-specific studies. Finally, important studies with primary gut microbiota samples delineated culture conditions for including gut commensal bacteria in the Gut Chip model.
