Iron as Environmental Factor in the Pathogenesis of Crohn's Disease-like Ileitis

Inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease (CD) are chronic disorders of the gastrointestinal tract. Iron replacement therapy is a common treatment in anemic CD patients, but oral iron supplements seem to be less tolerated. Pathogenesis of CD has been attributed to intestinal bacteria and environmental factors including dietary components like iron that trigger disease in a genetically predisposed host. The aim of this study was to characterize the interrelationship between iron, the gut microbiota and the development of chronic ileitis in a murine model of CD.Experimental results indicate that luminal iron sulfate deprivation in combination with systemic iron repletion inhibits the development of inflammation in TNF^{ Delta ARE/WTmice. The mechanisms imply changes in the gut microbiota as well as inhibition of endoplasmic reticulum stress and apoptosis in the intestinal epithelium.In conclusion, luminal iron may directly affect intestinal epithelial function or generate a pathological milieu in the intestine that triggers epithelial cell stress-associated apoptosis through changes in the microbial homeostasis. These data may offer a new possibility for the treatment of chronic intestinal inflammation and anemia in CD patients through modulation of the patients? iron status. In addition, oral replacement therapy with iron sulfate may trigger inflammatory processes associated with progression of CD-like ileitis and intravenous therapy should be preferred.