The gut-joint axis in juvenile idiopathic arthritis

Abstract Juvenile idiopathic arthritis (JIA) is an umbrella term for a group of oligo- and poly-arthritic conditions that develop before 16 years of age. While the exact pathophysiology of JIA is still unknown, both genetic and environmental factors are known to contribute to the development and severity of all JIA subtypes. Of the possible environmental factors involved, there is growing evidence that changes in intestinal homeostasis, or a ‘gut-joint axis’, can be observed in both animal models of arthritis and in adult arthritis. However, fewer studies have focused on whether similar processes contribute to JIA pathogenesis. In this review, we summarise the findings on the gut-joint axis in rheumatoid arthritis and experimental models of arthritis, highlighting comparisons with the studies that exist in JIA, with a separate focus on the JIA subtype Enthesitis-Related Arthritis (ERA). Notably, ERA is a spondyloarthropathy known to be associated with inflammatory bowel disease as a comorbidity. We also discuss the potential importance of perinatal factors, such as early antibiotics exposure or breastfeeding, in the gut-joint axis and whether they contribute to arthritis development in childhood. Lastly, we discuss how the gut-joint axis could be exploited therapeutically. Altogether, this review provides a comprehensive summary of the current state of knowledge regarding the gut-joint axis in JIA and highlights the importance of further study in this potentially therapeutic relevant area of paediatric rheumatology.