Boosting the Intestinal Mucosal Barrier to Emerging Pathobionts in Patients with Crohn´s Disease

Crohn´s disease (CD) is one of the main chronic inflammatory bowel diseases, with significant impacts on patients´ quality of life.

Current treatments lack therapeutic precision, compromising efficacy and safety.The pathogenesis of CD involves interplay of the intestinal microbiota and mucosal immunity at the mucosal barrier.

Typically, the initial inflammation in CD occurs as small aphtoid lesions of the follicle-associated epithelium (FAE), covering the Peyer’s patches.

Previous findings, including our own original work, identify the FAE as sites of microbial invasion in CD, but much remains unknown.Recently, pathobionts (resident microbes with pathogenic potential) have emerged as drivers of different disease traits in CD.

Our hypothesis is that patients with CD have a constitutively vulnerable FAE barrier where pathobionts invade and interact with immune cells generating inflammation.

The work will be based on our exclusive expertise for studying mucosal physiology in human FAE, access to human intestine, linked experiments in relevant models, and directed collaborations for proficiency in all details. Thereby our group is uniquely positioned to conduct the planned project.

Elucidating the means of invading, and triggering immune responses used by pathobionts will provide frontline data on several facets of FAE barrier function and suggest new ways to restore the barrier in CD, with the ultimate goal of curing this debilitating disease.