Studies of the Role of the Gastrointestinal Tract in Children with Juvenile Idiopathic Arthritis (JIA)

Sammanfattning: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children, but its cause is not fully established. Changes in the intestinal canal and an unfavourable composition of gut bacteria have been suggested as factors that can increase the risk of developing JIA and influence the disease course.This thesis investigated the possible association between JIA and changes in the intestinal canal.In a population-based study, 213 children diagnosed with JIA were screened for coeliac disease using immunoglobulin antibodies against tissue transglutaminase 2. Three children had a diagnosis of coeliac disease prior to screening and three previously undiagnosed cases were found through screening. The point prevalence for coeliac disease among children with JIA was 2.8%.In order to investigate if the composition of gut microbiotas in children with JIA differed from in healthy children and healthy siblings, 75 children with JIA were compared with 24 healthy controls, and eight children with JIA were compared pairwise with healthy siblings. Comparisons of microbiotas revealed trends towards altered relative abundances of taxa in children with JIA, but these were not significant when corrected for multiple comparisons.To examine the effects on gut microbiotas of treatment with methotrexate (MTX) or etanercept (ETN), faecal samples from 46 treatment-naïve children with JIA were compared with samples from children during treatment with MTX (n=29) or ETN (n=12). Paired comparisons were also made of children sampled both as treatment-naïve and during treatment with MTX (n=15) or ETN (n=7), including analyses of levels of faecal short-chain fatty acids. No significant differences were found after correction for multiple analyses.A pilot study investigated if improved clinical symptoms after interventions with exclusive enteral nutrition (EEN; n=6) or specific carbohydrate diet (SCD; n=10) in children with JIA were linked to changes in the gut microbiota. Faecal samples collected before the interventions were compared pairwise with samples collected after 3–5 weeks on the interventions. Both interventions altered microbiota composition, with a significant decrease in alpha-diversity and relative abundance of Actinobacteria during SCD.In conclusion, children with JIA most likely have an increased risk of coeliac disease and screening should be recommended. Faecal microbiota in children with JIA do not seem to differ compared with in healthy children or siblings. Treatment with MTX or ETN has no, or very limited, effect on the microbiota in faecal samples, but dietary interventions with EEN or SCD showed some changes in a pilot study.