Crucial role of intestinal barrier dysfunction in inflammatory bowel disease – identifying novel therapeutic targets

Inflammatory bowel diseases (IBD) are chronic intestinal diseases, with significant impacts on patients´ quality of life. Incidence is high and increasing, and current treatments lack therapeutic precision, compromising efficacy and safety.

The eitology of IBD is unknown but involves interplay of the intestinal microbiota and mucosal immunity at the mucosal barrier.

Recent findings, including our original work, demonstrate interactions between neuropeptides, eosinophils and mast cells in ulcerative colitis, and the follicle-associated epithelium (FAE) as a site of microbial invasion in Crohn’s disease, but much remains unknown.Our overarching hypothesis is that barrier dysfunction is a crucial step for initiation and perpetuation of mucosal inflammation and may be a novel therapeutic target in IBD.The work will be based on our exclusive expertise and methodologies for studying mucosal physiology in human biopsies and FAE, and our access to samples of inflamed and normal human intestine, complemented with directed collaborations for proficiency in all details.

Our group, thereby, is uniquely positioned to conduct the planned project.

We aim to uncover mechanisms of neuro-immune and gut microbial interactions with the human intestinal barrier during inflammation and stress.

This will provide frontline data on several facets of the regulation of barrier function and suggest new ways to restore the barrier in IBD, with the ultimate goal of curing these debilitating diseases.