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Adjudication committee
- First opponent: Professor Geneviève Veereman, University Hospital Brussels
- Second opponent: Professor Anders Paerregaard, Hvidovre Hospital
- Third member and chair of the evaluation committee: Professor Tom Øresland, University of Oslo
Chair of the Defence
Professor Anne Flem Jacobsen, University of Oslo
Principal Supervisor
Consultant Gøri Perminow, Oslo University Hospital
Summary
Pediatric inflammatory bowel disease (IBD) patients often present with an extensive disease distribution and an aggressive disease course. The disease course is unpredictable. We evaluated clinical factors, inflammatory biomarkers, serological markers and the composition of the gut microbiota in newly diagnosed patients under 18 years of age with IBD and in non-IBD symptomatic controls.
Half of our CD patients received biologic therapy within the first year. Biologic therapy was associated with higher inflammatory markers (CRP, ESR and fecal calprotectin), widespread disease, and more upper gastrointestinal involvement. Positive Anti- Saccharomyces Cerevisiae antibodies (ASCA) and/or negative perinuclear antineutrophil cytoplasmic antibodies (pANCA) status was associated with early initiation of biologic therapy in CD patients. ASCA serology was stable, regardless of treatments received, pANCA status declined after therapy in UC.
Fecal microbiota profiles could distinguish healthy children from symptomatic patients, but the microbiota profiles were similarly disturbed (dysbiotic) in IBD and non-IBD symptomatic patients. Severe dysbiosis in IBD was associated with extensive disease, stricturing and penetrating CD, biologic therapy, and lack of mucosal healing. The dysbiosis persisted after therapy, regardless of treatments and remission status. We found that pediatric IBD patients with widespread disease, high inflammatory markers in blood and feces, positive serologic markers and a disturbed gut microbiota have a high probability of an aggressive disease course with a need for surgery and biologic therapy.
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