© Laure Maes
Persistent fatigue severely affects the quality of life of IBD patients and reduces their ability to work. Although IBD patients, even when in clinical remission, report fatigue as one of the most disabling symptoms of their chronic disease, disease management is often only focused on attenuating gastrointestinal symptoms. In order to develop effective therapeutic interventions, a better understanding of what is causing IBD-associated fatigue is required. Therefore, the goal of this project is to develop a human gut-blood-brain in vitro model to explore the impact of active and extinguished gut inflammation on brain and brain barrier function.
In this project, a human gut-blood-brain in vitro model will be established based on organ-on-chip technology. Acute and extinguished inflammation will be induced in the gut compartment by adding a mix of pro-inflammatory cytokines or supernatant extracted from stool samples of IBD patients. The effect of inflammation will be evaluated on the gut-blood, the blood-cerebrospinal fluid barrier and the brain at protein and gene expression level. The obtained data will be compared to an experimental colitis model.
The majority of fundamental research on IBD-associated fatigue is based on animal models, since in vitro models are usually too reductionist to mimic complex diseases. However, the emerging multi-organ-on-chip models have been shown to be promising tools for the study of multi-organ and tissue interactions and could therefore complement in vivo data. The proposed in vitro model can be used to identify new therapeutic targets to tackle persistent fatigue, which could be a first step towards treatment development.
We expect to finish the project and deliver a manuscript within 2 years.