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FASEB J. 2020 Feb;34(2):2929-2943. doi: 10.1096/fj.201902396R. Epub 2019 Dec 29.

Impact of dietary manganese on experimental colitis in mice.

Author information

1
Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA.
2
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
3
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
4
Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.

Abstract

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

PMID:
31908045
DOI:
10.1096/fj.201902396R

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