Abstract
The gut microbiota, a vast community of symbiotic microorganisms inhabiting our gut, has been recognized as a key-lever for human health, shaping immune system resilience and being essential for immunological homeostasis throughout the life course. Gut microbiota composition may influence both initiation and/or perpetuation of intestinal inflammation, but recent research has highlighted its contribution to both rising and progression of protean non-intestinal inflammatory diseases: indeed, a perturbation of host-associated microbiota during critical developmental stages like early childhood can directly condition many cellular dynamics and impact long-term health. This narrative review explores the interactions among gut microbiota, physiologic healthy equilibrium, dysbiosis, and immune-mediated non-intestinal inflammatory diseases occurring in childhood, such as inflammasome-based disorders, juvenile idiopathic arthritis, Kawasaki disease, and IgA vasculitis, focusing on how microbial changes may alter disease outcomes and suggesting potentially novel therapeutic approaches. Additionally, this review examines the evolution of immune recognition mechanisms and their role in maintaining the gut microbiota-host mutualism as a result of millennia of human co-evolution with the microbial counterpart.