Diet plays a significant role in the pathogenesis of inflammatory bowel disease (IBD). A recent epidemiological study has shown an inverse relationship between nutritional manganese (Mn) status and IBD patients. Mn is an essential micronutrient required for normal cell function and physiological processes. To date, the roles of Mn in intestinal homeostasis remain unknown and the contribution of Mn to IBD has yet to be explored. Here, we provide evidence that Mn is critical for the maintenance of the intestinal barrier and that Mn deficiency exacerbates dextran sulfate sodium (DSS)-induced colitis in mice. Specifically, when treated with DSS, Mn-deficient mice showed increased morbidity, weight loss, and colon injury, with a concomitant increase in inflammatory cytokine levels and oxidative and DNA damage. Even without DSS treatment, dietary Mn deficiency alone increased intestinal permeability by impairing intestinal tight junctions. In contrast, mice fed a Mn-supplemented diet showed slightly increased tolerance to DSS-induced experimental colitis, as judged by the colon length. Despite the well-appreciated roles of intestinal microbiota in driving inflammation in IBD, the gut microbiome composition was not altered by changes in dietary Mn. We conclude that Mn is necessary for proper maintenance of the intestinal barrier and provides protection against DSS-induced colon injury.
Keywords: colitis; gut microbiota; inflammatory bowel disease; manganese; tight junction.
© 2019 Federation of American Societies for Experimental Biology.
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- R01 DK118023/DK/NIDDK NIH HHS/United States
- R01 DK095201/DK/NIDDK NIH HHS/United States
- R01 NS089896/NS/NINDS NIH HHS/United States
- Crohn's and Colitis Foundation (Crohn's & Colitis Foundation)
- 5P30DK034933/HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)