Persistent fatigue is a commonly reported symptom among patients with inflammatory bowel disease which often impairs work productivity and reduces the quality of life. Since little is known about the etiopathogenesis of IBD-associated fatigue, there is currently no effective treatment. A better understanding of the pathophysiology of IBD-associated fatigue is required. In vitro models are usually too reductionist to mimic complex diseases, but the emerging multi-organ microphysiological systems have been shown to be promising tools to study multi organ and tissue interactions.

The aims of this study are:

Objective 1. The establishment and characterization of a model for the in vitro study of gut-blood-brain communication based on organ-on-a-chip technology;

Objective 2. The exploration of the impact of low-grade gut inflammation on gut-blood barrier, blood-cerebrospinal fluid barrier and brain function.

In this project, a human gut-blood-brain in vitro model will be established based on cutting edge organ-on-a-chip technology. Each compartment will be individually optimized and characterized. Subsequently, the effect of connecting the different compartments with each other will be studied. At last, low-grade inflammation will be induced in the gut compartment to study molecular alterations on the gut-blood and blood-cerebrospinal fluid barriers and ultimately brain cells. Together, this approach will shed light on how neuroinflammation is induced upon intestinal inflammation.