Long-term iron deficiency and iron supplementation exacerbate acute DSS-induced colitis and are associated with significant dysbiosis

Patients taking oral iron supplementation often suffer from gastrointestinal side effects. We have previously shown that acute alterations in oral iron exacerbate dextran sodium sulphate (DSS) induced colitis and are associated with dysbiosis. As patients take iron supplementation for long periods, we asked whether this too would influence colitis and the microbiome. We assessed the impact of long-term changes in dietary iron, by feeding chow containing 100ppm, 200ppm and 400ppm (reflecting a deficient, normal or supplemented diet, respectively) for up to 9 weeks to female wild-type C57BL/6 (WT) mice in presence or absence of chronic colitis, or acute colitis induced after 8 weeks, induced by DSS. Assessment was made based on (i) clinical and histological severity of colitis, and (ii) faecal microbial diversity, as assessed by sequencing the V4 region of 16S rRNA. In mice with long term changes to their dietary iron, reduced iron intake (100ppm iron diet) was associated with increased weight loss and histology scoring in the acute colitis model. Chronic colitis was not influenced by altering dietary iron however there was a clear change in the faecal microbiome in the 100 and 400ppm iron DSS-treated groups and in controls consuming the 400ppm iron diet. Proteobacteria levels increased significantly at day-63 compared to baseline and Bacteroidetes levels decreased in the 400ppm iron DSS group at day-63 compared to baseline; mirroring our previously published work in acute colitis. Long term dietary iron alterations clearly affects gut microbiota signatures but do not appear to exacerbate chronic colitis. However, acute colitis is exacerbated by changes in dietary iron. More work is needed to understand the impact of iron supplementation of the pathologenesis of IBD and rise that possiblity that the change in the microbiome, in patients with colitis, is a consequence of the increase in luminal iron and not simply the presence of colitis.