Low Dietary Manganese Levels Exacerbate Experimental Colitis in Mice

Abstract

Abstract Objectives Inflammatory Bowel Disease (IBD), including Crohn's disease and ulcerative colitis, is a family of chronic inflammatory disorders of the gastrointestinal tract that affects over 3 million Americans. Diet and micronutrient intake plays a critical role in the pathogenesis of IBD. A recent epidemiological study showing an inverse relationship between nutritional manganese (Mn) status and IBD patients. Mn is an essential micronutrient required for normal growth and physiological processes. To date, the roles of Mn in the maintenance of intestinal health remain unknown, and the contribution of dietary Mn to IBD has yet to be explored. The goal of the present study is to determine the effects of dietary Mn on induced colitis in mice. Methods To investigate whether dietary Mn alters IBD progression in a dose-dependent manner, mice were fed purified diets containing either deficient, very low, low, or sufficient concentrations of Mn (0, 3, 15, or 35 ppm, respectively). Colitis was induced by providing mice drinking water containing 3% dextran sulfate sodium (DSS) for 6 days (inflammatory phase) followed by providing regular drinking water for 7 days (recovery phase). Results Upon treatment with DSS, the mice fed deficient, very low, and low dietary Mn showed increased morbidity, weight loss, and colon injury in a dose-dependent manner compared to the mice fed sufficient dietary Mn. Inflammation and oxidative damage was exacerbated in the deficient, very low, and low dietary Mn groups, which was displayed through greater spleen weights and elevated inflammatory cytokine levels. In contrast, mice fed sufficient dietary Mn showed greater tolerance to DSS-induced experimental colitis. Strikingly, even in the absence of DSS-induced colitis, mice with deficient intakes of dietary Mn displayed increases in gut permeability and losses in tight junction protein function while mice fed sufficient intakes of dietary Mn maintained intestinal integrity. Conclusions This study provides the first evidence that deficient, very low, and low levels of dietary Mn may exacerbate intestinal injury and inflammation dose-dependently in an experimental colitis model. These findings suggest that sufficient dietary Mn plays a critical role in intestinal cell barrier function, which may act as a protective mechanism against DDS-induced acute colitis in mice. Funding Sources NIH.