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P689. Iron supplemented diet protects against chronic immune mediated colitis in mice

N. Maharshak1, M. Ellermann1, R. Gharaibeh2, W. Sha2, E. Perez-Chanona3, K. Whitehead1, C. Jobin1, A. Fodor2, S.E. Plevy1, R.B. Sartor1, 1University of North Carolina, Department of Immunology and Microbiology, Chapel Hill, United States, 2University of North Carolina, Department of Bioinformatics and Genomics, Charlotte, United States, 3University of North Carolina, Department of Pharmacology, Chapel Hill, United States

Background

A sizable portion of IBD patients receive oral iron preparations to treat anemia, but the effect of iron on enteric inflammation is uncertain. In animal studies, an iron deficient diet is protective against the development of colitis. However, the clinical relevance of these studies is unclear given that iron deficient diets are rarely encountered in Western society. Indeed, human studies have failed to show increased disease severity in IBD patients treated with oral iron supplementation.

We aimed to study the effects of clinically relevant doses of dietary iron on inflammation in mice. We hypothesized that iron will increase severity of colitis through its effects on enteric microbial populations.

Methods

IL-10−/− germ-free mice were inoculated with feces from a conventionally housed mouse and placed on iron deficient, iron sufficient or iron supplemented isocaloric diets (<10, 35 or 200 ppm iron/kg respectively) for four weeks.

In cohort 1 (n = 8/group), clinical severity score (0–3) was assessed. In cohort 2 (n = 5/group), severity of colitis was assessed through colon histology score (0–12) and IL-12 p40 levels. Bacterial 16S ribosomal RNA from stool was sequenced using the Illumina platform and bacterial specific qPCR were performed on stool and mucosal samples.

Results

Mice maintained on the iron supplemented diet developed significantly less severe colitis compared with mice on the iron sufficient diet as assessed through clinical score (0.33 vs 1.15, P < 0.01), histology (3.16 vs 6.28, P < 0.05), serum IL-12 p40 levels (2181 vs 5483 pg/ml, P < 0.05) and colonic IL-12 p40 levels (1683 vs 3044 pg/100 mg tissue, P = 0.07). The iron deficient diet mediated non-significant protection against colitis in the two cohorts.

While compositional changes of the enteric bacteria did not explain the findings, targeted qPCR studies revealed a decreased total mucosal bacteria load (6.25 fold decrease, P < 0.05) and a higher proportion of mucosa associated F. prausnitzii (2.3 fold increase, P < 0.05) in mice maintained on the iron supplemented diet compared to the iron sufficient diet. In vitro studies supported that iron enhanced growth of F. prausnitzii.

Conclusion

The iron supplemented diet protected against colitis in mice, perhaps by decreasing mucosal bacterial load and increasing the proportion of iron responsive bacteria such as F. prausnitzii, which have protective properties.

These findings may be relevant to human studies as iron supplementation was assumed, perhaps mistakenly, to aggravate colitis.