Paediatric inflammatory bowel disease Moving towards tailored diagnostic and treatment approaches

Paediatric inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic disorder with relapsing-remitting inflammation of the gastrointestinal tract, affecting around 8% of patients before the age of 18. While the exact cause remains unclear, the interplay of gut microbiota, genetics, environment, and immune factors is hypothesised. The diagnostic work-up of paediatric IBD involves clinical symptoms along with laboratory, radiologic, endoscopic, and histologic findings. However, current biomarkers, with faecal calprotectin as the most commonly used marker, lack specificity. The first part of this thesis investigates the potential of faecal gut microbiota and metabolomics as non-invasive diagnostic biomarkers. Findings suggest altered metabolomic profiles in children with IBD, with specific amino acids showing promise for differentiation between IBD and controls. The second part focuses on optimising treatment with thiopurines and infliximab and evaluating surveillance strategies. It was shown that accelerated infliximab infusions without an intrahospital observation period were safe. Additionally, we observed variability in surveillance practices for colorectal cancer in paediatric UC patients among Dutch gastroenterologists, proposing the need for standardised guidelines. The third part aims to establish a shared research agenda, involving patients, caregivers, and healthcare professionals. The top 10 research priorities are identified, covering aspects including the cause and management of fatigue, IBD pathophysiology, non-invasive diagnostic strategies, and coping support.