Vitamin D deficiency promotes epithelial barrier dysfunction and intestinal inflammation

J Infect Dis. 2014 Oct 15;210(8):1296-305. doi: 10.1093/infdis/jiu235. Epub 2014 Apr 21.


Background: Vitamin D, an important modulator of the immune system, has been shown to protect mucosal barrier homeostasis. This study investigates the effects of vitamin D deficiency on infection-induced changes in intestinal epithelial barrier function in vitro and on Citrobacter rodentium-induced colitis in mice.

Methods: Polarized epithelial Caco2-bbe cells were grown in medium with or without vitamin D and challenged with enterohemorrhagic Escherichia coli O157:H7. Barrier function and tight junction protein expression were assessed. Weaned C57BL/6 mice were fed either a vitamin D-sufficient or vitamin D-deficient diet and then infected with C. rodentium. Disease severity was assessed by histological analysis, intestinal permeability assay, measurement of inflammatory cytokine levels, and microbiome analysis.

Results: 1,25(OH)2D3 altered E. coli O157:H7-induced reductions in transepithelial electrical resistance (P < .01), decreased permeability (P < .05), and preserved barrier integrity. Vitamin D-deficient mice challenged with C. rodentium demonstrated increased colonic hyperplasia and epithelial barrier dysfunction (P < .0001 and P < .05, respectively). Vitamin D deficiency resulted in an altered composition of the fecal microbiome both in the absence and presence of C. rodentium infection.

Conclusions: This study demonstrates that vitamin D is an important mediator of intestinal epithelial defenses against infectious agents. Vitamin D deficiency predisposes to more-severe intestinal injury in an infectious model of colitis.

Keywords: barrier function; colitis; dysbiosis; microbiome; vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caco-2 Cells
  • Calcitriol / pharmacology*
  • Citrobacter rodentium
  • Colitis / etiology
  • Enterobacteriaceae Infections / microbiology
  • Enterohemorrhagic Escherichia coli
  • Escherichia coli Infections
  • Feces / microbiology
  • Humans
  • Inflammation / metabolism*
  • Intestinal Diseases / metabolism*
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / physiopathology*
  • Mice
  • Mice, Inbred C57BL
  • Vitamin D Deficiency / metabolism
  • Vitamin D Deficiency / pathology*


  • Calcitriol