Giuseppe
Emeritus
[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]
Vitamin D Deficiency Promotes Epithelial Barrier Dysfunction and Intestinal Inflammation
Amit Assa 1,2, Linda Vong 1, Lee J Pinnell 1, Naama Avitzur 1, Kathene C. Johnson-Henry 1 and Philip M. Sherman 1,2,3,*
Author Affiliations: <SUP>1</SUP>Cell Biology Program, Research Institute <SUP>2</SUP>Department of Paediatrics, Hospital for Sick Children <SUP>3</SUP>University of Toronto, Toronto, Ontario, Canada
*Correspondence: Philip M. Sherman, MD, FRCPC, Cell Biology Program, Research Institute, Hospital for Sick Children, Room 8263, 555 University Avenue, Toronto, ON, Canada M5G 1X8. Tel.1-416-813-7733, Fax.1-416-813-4972, Email: Philip.sherman@sickkids.ca
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 was assessed. Weaned C57BL/6 mice were fed either a vitamin D sufficient or deficient diet and then infected with C. rodentium. Disease severity was assessed by histological analysis, intestinal permeability assay, inflammatory cytokines and microbiome analysis.
Results.
1,25(OH)<SUB>2</SUB>D<SUB>3</SUB> altered E. coli O157:H7-induced reductions in transepithelial electrical resistance (p<0.01), decreased permeability (p<0.05) and preserved barrier integrity. Vitamin D deficient mice challenged with C. rodentium demonstrated increased colonic hyperplasia and epithelial barrier dysfunction (p<0.0001 and p<0.05, 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.
Received January 31, 2014. Revision received April 7, 2014. Accepted April 11, 2014.
? The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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Vitamin D Deficiency Promotes Epithelial Barrier Dysfunction and Intestinal Inflammation
Amit Assa 1,2, Linda Vong 1, Lee J Pinnell 1, Naama Avitzur 1, Kathene C. Johnson-Henry 1 and Philip M. Sherman 1,2,3,*
Author Affiliations: <SUP>1</SUP>Cell Biology Program, Research Institute <SUP>2</SUP>Department of Paediatrics, Hospital for Sick Children <SUP>3</SUP>University of Toronto, Toronto, Ontario, Canada
*Correspondence: Philip M. Sherman, MD, FRCPC, Cell Biology Program, Research Institute, Hospital for Sick Children, Room 8263, 555 University Avenue, Toronto, ON, Canada M5G 1X8. Tel.1-416-813-7733, Fax.1-416-813-4972, Email: Philip.sherman@sickkids.ca
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 was assessed. Weaned C57BL/6 mice were fed either a vitamin D sufficient or deficient diet and then infected with C. rodentium. Disease severity was assessed by histological analysis, intestinal permeability assay, inflammatory cytokines and microbiome analysis.
Results.
1,25(OH)<SUB>2</SUB>D<SUB>3</SUB> altered E. coli O157:H7-induced reductions in transepithelial electrical resistance (p<0.01), decreased permeability (p<0.05) and preserved barrier integrity. Vitamin D deficient mice challenged with C. rodentium demonstrated increased colonic hyperplasia and epithelial barrier dysfunction (p<0.0001 and p<0.05, 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.
Received January 31, 2014. Revision received April 7, 2014. Accepted April 11, 2014.
? The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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