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We focus on research on inflammation in inflammatory bowel disease (IBD) and other diseases with severe intestinal inflammation in humans. The research is centred on the biology of intestinal inflammation at the mucosal level, the organ/intestinal level, and the individual level:
The mucosal level
Inflammation in IBD follows a relapsing-remitting disease pattern. We study the mechanisms that initiates these flares because therapies targeting this would improve long-term outcomes. We have developed the human intestinal injury model to study differences in early injury response (6 – 48 h post-injury) in the normal intestine and in quiescent IBD. The method has identified an IBD-specific macroscopic (by endoscopy), microscopic (by Geboes score), and molecular innate hyper-response, along with IBD-type changes in injury niche microbiota and lipid metabolome. We work on understanding how the hyper-response is initiated to identify trigger-specific therapeutic targets.
Basically, active IBD is a failure to achieve mucosal healing. Patients obtaining mucosal healing irrespective of the treatment have good short- and long-term prognosis. Looking at epithelial restitution in IBD we found induction of cytoprotective pathways (cIAPs, cFLIP, PGE2 responses) that might improve initial restitution processes but impair differentiation and full regeneration and block response to biological therapy. We found lipid metabolomes specific for delayed regeneration. We aim to understand the dynamics of mucosal healing and look at late phases of injury responses – mucosal regeneration (2-7 days post-injury) to identify regenerative targets to improve mucosal healing.
The intestinal level
Patients admitted with acute severe IBD and IBD-type inflammation after immune checkpoint therapy for cancer have a high risk disease phenotype (acute colectomies, morbidity, mortality). Early identification of high-risk patients will allow accelerated therapy to improve outcome. We study mucosal markers, peripheral blood markers and inflammation burden measured by intestinal high resolution ultrasound imaging (IUS; one prospective and one investigator initiated randomized clinical trial). We found IUS to be highly predictive of later outcome as one of the first data coming out of these ongoing studies.
The individual level
Clinical, biochemical, and genetic profiling of IBD patients is surprisingly poor at predicting complicated disease course and intestinal damage. We have done studies showing that inflammatory biologic profiles predict outcome of therapy and may guide selection of therapy. We are key or head centre for three multicenter prospective studies looking at mucosal/microbial/blood biological markers for disease course for IBD-patients (the Danish IBD Biobank Project (DIB), the IBD Prognosis Study, and a IBD-fibrosis study).
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