Translational investigation of the pathophysiological role of intestinal barrier dysfunction and microbiota in juvenile idiopathic arthritis Juvenile idiopathic arthritis (JIA) is the most common childhood-onset chronic rheumatic disease. The cause of JIA remains unknown. A growing number of evidence suggests that the intestinal microbiota and intestinal barrier function are altered in JIA patient. However, a mechanistic link between alterations of intestinal immune homeostasis and JIA has not been established. Proposed study: Here we propose to investigate the functional role of the intestinal barrier and microbiota in the pathophysiology of early onset JIA. We will conduct a translational study combining ex vivo investigations using patients’ biomaterials and functional studies in murine arthritis models transplanted with human feces. Objectives: 1) Evaluation of intestinal barrier function and fecal microbiota in JIA patients versus healthy controls. 2) Identification of serum biomarkers associated to barrier dysfunction and alteration of intestinal microbiota. 3) Evaluation of the effect of the microbiota from patients and controls on the intestinal barrier function and development of arthritis in murine arthritis models transplanted with human microbiota. Feasibility: The federation of partners with strong expertise in clinical research, biomedical research and basic science guarantees the success of this project. This translational study articulates with a clinical trial. It therefore benefits from already established circuits with regard to patient recruitment, collection and processing of biomaterials. Repercussion: The demonstration that intestinal microbiota and alterations of the intestinal barrier function are the key event for the development of JIA may pave the way to new therapeutic strategies. The identified biomarkers may allow stratification of patients eligible for such treatments.