TY - JOUR
T1 - Vitamin D deficiency in mice impairs colonic antibacterial activity and predisposes to colitis
AU - Lagishetty, Venu
AU - Misharin, Alexander V.
AU - Liu, Nancy Q.
AU - Lisse, Thomas S.
AU - Chun, Rene F.
AU - Ouyang, Yi
AU - McLachlan, Sandra M.
AU - Adams, John S.
AU - Hewison, Martin
PY - 2010/6
Y1 - 2010/6
N2 - 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 ± 3.1 vs. 45.6 ± 4.2 pg/ml), greater DSS-induced weight loss (9 vs. 5%), increased colitis (4.71 ± 0.85 vs. 1.57 ± 0.18), and splenomegaly relative to mice on vitamin D-sufficient chow.DNAarray 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.
AB - 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 ± 3.1 vs. 45.6 ± 4.2 pg/ml), greater DSS-induced weight loss (9 vs. 5%), increased colitis (4.71 ± 0.85 vs. 1.57 ± 0.18), and splenomegaly relative to mice on vitamin D-sufficient chow.DNAarray 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.
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U2 - 10.1210/en.2010-0089
DO - 10.1210/en.2010-0089
M3 - Article
C2 - 20392825
AN - SCOPUS:77954521879
SN - 0013-7227
VL - 151
SP - 2423
EP - 2432
JO - Endocrinology
JF - Endocrinology
IS - 6
ER -