Vitamin D Deficiency in Mice Impairs Colonic Antibacterial Activity and Predisposes to Colitis

• DOI: 10.1210/en.2010-0089
• Publication Date: 2010-04-15T01:34:10Z
• Authors: Venu Lagishetty; Alexander V. Mish...; Nancy Q. Liu; Thomas S. Lisse; Rene F. Chun; Yi Ouyang; Sandra M. McLachlan; John S. Adams; Martin Hewison
• Keywords: DNA, Bacterial; 0301 basic medicine; 2. Zero hunger; Colon; Reverse Transcriptase Polymerase Chain Reaction; Dextran Sulfate; Ribonuclease, Pancreatic; Colitis; Flow Cytometry; Vitamin D Deficiency; Immunohistochemistry; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Splenomegaly; Weight Loss; Animals; Vitamin D; Oligonucleotide Array Sequence Analysis

Vitamin D insufficiency is a global health issue. Although classically associated with rickets, low vitamin levels have also been linked to aberrant immune function and problems such as inflammatory bowel disease (IBD). To test the hypothesis that impaired status predisposes IBD, 8-wk-old C57BL/6 mice were raised from weaning on D-deficient or D-sufficient diets then treated dextran sodium sulphate (DSS) induce colitis. showed decreased serum of precursor 25-hydroxyvitamin D3 (2.5 ± 0.1 vs. 24.4 1.8 ng/ml) active 1,25-dihydroxyvitamin (28.8 3.1 45.6 4.2 pg/ml), greater DSS-induced weight loss (9 5%), increased colitis (4.71 0.85 1.57 0.18), splenomegaly relative chow. DNA array analysis colon tissue (n = 4 mice) identified 27 genes consistently (P < 0.05) up-regulated down-regulated more than 2-fold in mice, absence This included angiogenin-4, an antimicrobial protein involved host containment enteric bacteria. Immunohistochemistry confirmed colonic angiogenin-4 was significantly even Moreover, same animals elevated (50-fold) bacteria tissue. These data show for first time simple deficiency via dysregulated activity homeostasis may be pivotal mechanism linking IBD humans.