Development of high throughput microfluidic gut-on-a-chip models for drug discovery and target validation in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a group of chronic relapsing inflammatory diseases of the gastrointestinal tract. Diseased patients have currently limited options in terms of treatment caused by the lack of physiologically relevant models to study IBD. Recently, the organ-on-a-chip technology has offered new insights into IBD modelling that could alleviate some of the limitations of the models currently used. This study reports the development of two novel gut-on-a-chip microfluidic platforms that that can uniquely contribute to the advancement of research in the IBD field.

The first model, robust and simple, is composed of the human cell line Caco-2 submitted to a clean inflammatory cocktail. The epithelium displayed a disrupted organization and an increased cell activation denoted by elevated cytokine release. The second model, more complex and physiologically relevant, integrates patient-derived intestinal organoids together with human macrophages, triggered by a mixture of cytokines and bacterial components.

We show that these gut-on-a-chip models can be used to support daily drug discovery activities in IBD, both at the target validation and compound testing levels. Our results set the ground to improved, more relevant models of the human intestine, in order to better understand this complex pathology, which could in turn lead to the discovery of more efficient and accurate treatments for IBD patients.