Vitamin D deficiency predisposes to adherent-invasive escherichia coli-induced barrier dysfunction and experimental colonic injury

Amit Assa, Linda Vong, Lee J. Pinnell, Jaana Rautava, Naama Avitzur, Kathene C. Johnson-Henry, Philip M. Sherman

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Background: Adherent-invasive Escherichia coli (AIEC) colonization has been strongly implicated in the pathogenesis of Crohn's disease. Environmental triggers such as vitamin D deficiency have emerged as key factors in the pathogenesis of inflammatory bowel diseases. The aim of this study was to investigate the effects of 1,25(OH)2D3 on AIEC infection-induced changes in vivo and in vitro. Methods: Barrier function was assessed in polarized epithelial Caco-2-bbe cells grown in medium with or without vitamin D and challenged with AIEC strain LF82. Weaned C57BL/6 mice were fed either a vitamin D-sufficient or -deficient diet for 5 weeks and then infected with AIEC, in the absence and presence of low-dose dextran sodium sulphate. Disease severity was assessed by histological analysis and in vivo intestinal permeability assay. Presence of invasive bacteria was assessed by transmission electron microscopy. Results: Caco-2-bbe cells incubated with 1,25(OH)2D3 were protected against AIEC-induced disruption of transepithelial electrical resistance and tightjunction protein redistribution. Vitamin D-deficient C57BL/6 mice given a course of 2% dextran sodium sulphate exhibited pronounced epithelial barrier dysfunction, were more susceptible to AIEC colonization, and showed exacerbated colonic injury. Transmission electron microscopy of colonic tissue from infected mice demonstrated invasion of AIEC and fecal microbiome analysis revealed shifts in microbial communities. Conclusions: These data show that vitamin D is able to mitigate the deleterious effects of AIEC on the intestinal mucosa, by maintaining intestinal epithelial barrier homeostasis and preserving tight-junction architecture. This study highlights the association between vitamin D status, dysbiosis, and Crohn's disease.

Original languageEnglish
Pages (from-to)297-306
Number of pages10
JournalInflammatory Bowel Diseases
Volume21
Issue number2
DOIs
StatePublished - 1 Jan 2015
Externally publishedYes

Keywords

  • Adherent-invasive E. coli
  • Colonization
  • Crohn's disease
  • Environmental factors
  • Microbiota

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

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