title: Vitamin D deficiency promotes epithelial barrier dysfunction and intestinal inflammation.
abstract: 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.
authors.affiliation: Cell Biology Program, Research Institute Department of Paediatrics, Hospital for Sick Children.
authors.forename: Amit
authors.initials: A
authors.lastname: Assa
authors.affiliation: Cell Biology Program, Research Institute.
authors.forename: Linda
authors.initials: L
authors.lastname: Vong
authors.affiliation: Cell Biology Program, Research Institute.
authors.forename: Lee J
authors.initials: LJ
authors.lastname: Pinnell
authors.affiliation: Cell Biology Program, Research Institute.
authors.forename: Naama
authors.initials: N
authors.lastname: Avitzur
authors.affiliation: Cell Biology Program, Research Institute.
authors.forename: Kathene C
authors.initials: KC
authors.lastname: Johnson-Henry
authors.affiliation: Cell Biology Program, Research Institute Department of Paediatrics, Hospital for Sick Children University of Toronto, Canada.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Sherman
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002117:Calcitriol / Q000494:pharmacology*; D044082:Citrobacter rodentium; D003092:Colitis / Q000209:etiology; D004756:Enterobacteriaceae Infections / Q000382:microbiology; D054324:Enterohemorrhagic Escherichia coli; D004927:Escherichia coli Infections; D005243:Feces / Q000382:microbiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007410:Intestinal Diseases / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014808:Vitamin D Deficiency / Q000378:metabolism / Q000473:pathology*
chemical_list: D002117:Calcitriol
keywords: barrier function; colitis; dysbiosis; microbiome; vitamin D