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, Martin Hewison*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

162 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2423-2432
Number of pages10
JournalEndocrinology
Volume151
Issue number6
DOIs
StatePublished - Jun 2010

ASJC Scopus subject areas

  • Endocrinology

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