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P043. Microbial balances altered by restriction of dietary iron ameliorated immune-mediated colitis

T. Toyonaga1, M. Matsuura2, H. Nakase2, S. Yamada2, N. Minami2, Y. Honzawa2, T. Yoshino2, K. Okazaki1, T. Chiba2, 1Kansai Medical University, Department of Gastroenterology and Hepatology, Osaka, Japan, 2Kyoto University Hospital, Department of Gastroenterology and Hepatology, Kyoto, Japan

Background

Inflammatory bowel disease (IBD) is a chronic and relapsing-remitting inflammatory disorder characterized by recurrent intestinal inflammation. In addition to the excessive immune responses to commensal enteric bacteria, environmental factors are involved in the pathogenesis of IBD. Generally, iron is essential for the growth and virulence of most bacterial species. Previous epidemiologic studies reported the significant association between high content of iron in water supply and an increased incidence of IBD, and that oral, but not intravenous, iron supplementation increased disease activity in IBD. Taken together, dietary iron could be one of potential candidates for environmental factors in IBD. The aim of this study is to investigate the effect of dietary iron on intestinal inflammation and enteric microbiota using a murine experimental colitis model.

Methods

IL-10 knockout mice were fed with iron-deprived (<3.2 mg/kg) or iron-supplemented (200 mg/kg) diets immediately after weaning (n = 7 in each group, 4 weeks of age). Mice were housed in specific pathogen free conditions, and then sacrificed at 4 and 8 weeks after feeding these refined diets. We evaluated intestinal inflammation by blinded histologic scores, measured TNF-α and IL-12p40 secretion by colonic explant culture, and quantified IL-17 and IFN-γ secretion from unseparated mesenteric lymph node (MLN) cells stimulated with cecal bacterial lysate by enzyme-linked immune-sorbent assay (ELISA). In addition, we analyzed the compositional changes of enteric microbiota by terminal restriction fragment length polymorphisms (T-RFLPs), using cecal contents obtained from both groups at 8 weeks after feeding refined diets.

Results

Histologic scores were significantly lower in the iron-deprived diet group compared with in the iron-supplemented diet group (2.7±0.5 vs. 10.0±3.7 at 8 weeks, p < 0.05). Colonic TNF-α and IL-12p40 secretion were significantly lower in the iron-deprived diet group compared with in the iron-supplemented diet group (IL-12p40; 16.0±7.5 vs. 52.9±17.0 ng/mL at 8 weeks, p < 0.05). Both of IL-17 and IFN-γ secretion from MLN cells were lower in the iron-deprived diet group than in the iron-supplemented diet group. Cluster analysis of T-RFLPs showed distinct differences in the profiles of enteric microbiota between the iron-deprived and -supplemented diet groups.

Conclusion

Restriction of dietary iron attenuates colonic inflammation in IL-10 KO mouse with a compositional alteration of enteric microbiota.