Comparative analysis of dietary iron deprivation and supplementation in a murine model of colitis

Inflammatory bowel diseases are chronic inflammatory conditions with growing prevalence in western populations. Iron is an essential component of erythrocytes hemoglobin. Under the influence of elevated hepcidin production, iron is sequestered in cells during inflammation which, in turn, leads to iron restriction for red blood cell synthesis. As a consequence, iron deficiency and anemia of inflammation are the most prevalent extraintestinal complications in IBD patients. Iron deficiency is commonly treated with oral iron supplements, with limited efficacy as iron absorption is blunted during intestinal inflammation. Moreover, iron supplementation can cause intestinal complications, as previous studies have shown that it can worsen the inflammatory response. However, a comparative analysis of the effects of low, adequate, and high dietary iron content matching the iron supplementation given to patients has not been performed in mice. We therefore tested the impact of dietary iron deprivation and supplementation in a murine model of colitis induced by dextran sodium sulfate. We found that both dietary iron deprivation and supplementation were accompanied by a more severe inflammation with earlier signs of gastrointestinal bleeding compared to mice fed an iron-adequate diet. The manipulation of dietary iron led to a profound dysbiosis in the colon of control mice that differed depending on the dietary iron content. Analysis of this dysbiosis is in line with a pronounced susceptibility to colonic inflammation, thus questioning the benefit/risk balance of oral iron supplementation for IBD patients.