Am J Clin Nutr. 2008 Aug;88(2):582S-586S. Free article
Vitamin D Deficiency in Mice Impairs Colonic Antibacterial Activity and Predisposes to Colitis
Venu Lagishetty, Alexander V. Misharin, Nancy Q. Liu, Thomas S. Lisse, Rene F. Chun, Yi Ouyang, Sandra M. McLachlan, John S. Adams, and Martin Hewison
Orthopaedic Hospital Research Center (V.L., N.Q.L., T.S.L., R.F.C., J.S.A., M.H.) and Molecular Biology Institute (J.S.A., M.H.), University of California Los Angeles, Los Angeles, California 90095; Autoimmune Disease Unit (A.V.M., S.M.M.), Cedars-Sinai Research Institute and University of California Los Angeles School of Medicine, Los Angeles, California 90048; Department of Pathology (Y.O.), Veterans Affairs Medical Center, Long Beach, California 90822; and University of California Irvine (Y.O.), Irvine, California 92679
Vitamin D insufficiency is a global health issue. Although classically associated with rickets, low vitamin D levels have also been linked to aberrant immune function and associated health problems such as inflammatory bowel disease (IBD). To test the hypothesis that impaired vitamin D status predisposes to IBD, 8-wk-old C57BL/6 mice were raised from weaning on vitamin D-deficient or vitamin D-sufficient diets and then treated with dextran sodium sulphate (DSS) to induce colitis.
Vitamin D-deficient mice showed decreased serum levels of precursor 25-hydroxyvitamin D3 (2.5 ± 0.1 vs. 24.4 ± 1.8 ng/ml) and active 1,25-dihydroxyvitamin D3 (28.8 ± greater DSS-induced weight loss (9 vs. 5%), increased colitis (4.71 splenomegaly relative to mice on vitamin D-sufficient chow. DNA array analysis of colon tissue (n = 4 mice) identified 27 genes consistently (P ± 0.05) up-regulated or down-regulated more than 2-fold in vitamin D-deficient vs. vitamin D-sufficient mice, in the absence of DSS-induced colitis. This included angiogenin-4, an antimicrobial protein involved in host containment of enteric bacteria.
Immunohistochemistry confirmed that colonic angiogenin-4 protein was significantly decreased in vitamin D-deficient mice even in the absence of colitis. Moreover, the same animals showed elevated levels (50-fold) of bacteria in colonic tissue. These data show for the first time that simple vitamin D deficiency predisposes mice to colitis via dysregulated colonic antimicrobial activity and impaired homeostasis of enteric bacteria. This may be a pivotal mechanism linking vitamin D status with IBD in humans. (Endocrinology 151: 0000 – 0000, 2010)