Dietary vitamin D3 deficiency alters intestinal mucosal defense and increases susceptibility to Citrobacter rodentium-induced colitis.
Vitamin D deficiency affects more that 1 billion people worldwide. Although thought to increase risk of bacterial infections, the importance of vitamin D on host defense against intestinal bacterial pathogens is currently unclear since injection of the active form of vitamin D, 1,25(OH)2D3, increased susceptibility to the enteric bacterial pathogen Citrobacter rodentium by suppressing key immune/inflammatory factors. To further characterize the role of vitamin D during bacteria-induced colitis, we fed weanling mice either vitamin D3-deficient or vitamin D3-sufficient diets for 5 wk and then challenged them with C. rodentium. Vitamin D3-deficient mice lost significantly more body weight, carried higher C. rodentium burdens, and developed worsened histological damage. Vitamin D3-deficient mice also suffered greater bacterial translocation to extra-intestinal tissues, including mesenteric lymph nodes, spleen, and liver. Intestinal tissues of infected vitamin D3-deficient mice displayed increased inflammatory cell infiltrates as well as significantly higher gene transcript levels of inflammatory mediators TNF-α, IL-1β, IL-6, TGF-β, IL-17A, and IL-17F as well as the antimicrobial peptide REG3γ. Notably, these exaggerated inflammatory responses accelerated the loss of commensal microbes and were associated with an impaired ability to detoxify bacterial lipopolysaccharide. Overall, these studies show that dietary-induced vitamin D deficiency exacerbates intestinal inflammatory responses to infection, also impairing host defense.
Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; and.
Natasha R
NR
Ryz
Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; and.
Arion
A
Lochner
Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; and.
Kirandeep
K
Bhullar
Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; and.
Caixia
C
Ma
Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; and.
Tina
T
Huang
Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; and.
Ganive
G
Bhinder
Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; and.
Else
E
Bosman
Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; and.
Xiujuan
X
Wu
Division of Neonatology, Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Sheila M
SM
Innis
Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; and.
Kevan
K
Jacobson
Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; and bvallance@cw.bc.ca.
Bruce A
BA
Vallance
D000818:Animals; D058491:Bacterial Load; D018988:Bacterial Translocation; D002432:Cecum / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D002762:Cholecalciferol / Q000172:deficiency*; D044082:Citrobacter rodentium / Q000472:pathogenicity*; D003092:Colitis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D004756:Enterobacteriaceae Infections / Q000150:complications / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D005243:Feces / Q000382:microbiology; D005260:Female; D054884:Host-Pathogen Interactions; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008070:Lipopolysaccharides / Q000378:metabolism; D008810:Mice, Inbred C57BL; D000073718:Pancreatitis-Associated Proteins; D010766:Phosphorylation; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014808:Vitamin D Deficiency / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D015431:Weight Loss
D016207:Cytokines; D018836:Inflammation Mediators; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C490255:Reg3g protein, mouse; D002762:Cholecalciferol
Citrobacter rodentium; colitis; inflammation; segmented filamentous bacteria; vitamin D