Regional Gastrointestinal Permeability Patterns in Juvenile Idiopathic Arthritis: A Window into Subclinical Inflammation and Microbiota-Driven Disease Mechanisms

Highlights: What are the main findings? JIA patients may show altered gastrointestinal segmental sugar absorption despite globally normal intestinal permeability. What are the implication of the main findings? Permeability testing of different gastrointestinal tracts may provide a sensitive tool to uncover hidden mucosal abnormalities that are not captured by global indices. The exploratory findings of this study may support a role for the gut–joint axis and microbiota-driven mechanisms in JIA pathogenesis, with potential implications for early diagnosis and therapeutic targeting. Objectives: To assess gastrointestinal permeability (GP) in children with Juvenile Idiopathic Arthritis (JIA) using a segment-specific sugar probe approach to assess gastric, small intestinal, and colonic permeability, and to determine whether GP alterations are associated with disease activity. Methods: This prospective study included 30 children with JIA and 22 healthy controls who underwent a validated multi-sugar absorption test. Urinary excretion of sucrose, lactulose, mannitol, and sucralose was measured to evaluate gastric, small intestinal, and colonic permeability. All JIA patients had discontinued immunosuppressive therapy for at least three months before testing. None had a relapse of the disease. Disease activity was assessed using the Juvenile Arthritis Disease Activity Score (JADAS10). Comparisons were conducted between patients and controls and between remission and active disease groups. Results: None of the participants reported gastrointestinal manifestations. The lactulose/mannitol (LA/MA) ratio, a global index of small intestinal permeability, showed no significant difference between JIA patients and controls, suggesting preserved overall barrier function. However, urinary excretion of lactulose, mannitol, and sucralose was significantly higher in JIA patients, while sucrose excretion was significantly lower, indicating segment-specific alterations in small intestinal, colonic, and gastric permeability. These abnormalities were consistently present, even in patients in clinical remission. No statistically significant differences were observed between remission and active disease groups, though a trend toward increased permeability was noted in the latter. Conclusions: Children with JIA exhibit segmental GP alterations that persist independently of clinical disease activity. Despite the relatively small population, this exploratory study suggests subclinical mucosal dysfunction and the need for further investigation into how the gut–joint axis may be playing a role in JIA pathogenesis, including via intestinal microbiota.