Indeed, NOX1, NOX2, and DUOX2 deficiencies have been associated with a higher risk of developing pediatric123 and very early onset IBD.124, 125, 126 Furthermore, patients suffering from chronic granulomatous disease, a rare disorder characterized by deficiency in phagocytic NOX function, have a high risk to develop IBD,127,128 suggesting that defective O2•- production can lead to IBD and therefore antioxidant doses should be carefully adjusted for these patients. This evidence concerns the gene DUOX2 and inflammatory bowel disease.