Maternal and early-life vitamin D deficiency enhances allergic reaction in an ovalbumin-sensitized BALB/c mouse model

  • Jiang Wu
  • Yan Zhong
  • Xiuhua Shen
  • Kefeng Yang
  • Wei Cai
Keywords: vitamin D deficiency, food allergy, Treg cells, tight junctions, intestinal epithelial barrier


Background: Recent studies have shown that vitamin D deficiency may contribute to the high prevalence of food allergy but the underlying mechanisms are far from clear.

Objective: The present study was designed to investigate the effect of maternal and early-life vitamin D deficiency in the development of food allergy.

Design: BALB/c mice were treated with ovalbumin (OVA) to trigger allergic reactions, under vitamin D-deficient (by maternal and early-life feeding of vitamin D deprived chow diet) or vitamin D-sufficient conditions.

Results: Increased occurrence and severity of allergic diarrhea as well as decreased rectal temperature were observed after OVA sensitization. For vitamin D deficiency groups, OVA-specific IgE and IL-4 levels were significantly increased, while IFN-γ levels were unchanged. Vitamin D deficiency also attenuated the structure of small intestinal villi and decreased the expression of the tight junction protein between adjacent epithelial cells and the percentages of CD4+CD25+Foxp3+Treg cell in spleen and mesenteric lymph nodes.

Conclusions: Maternal and early-life vitamin D deficiency have notable influence on the susceptibility to food allergy, which may relate with the reduced population of Treg cell and the dysfunction of intestinal epithelial barrier.


Download data is not yet available.


  1. Kennel KA, Drake MT, Hurley DL. Vitamin D deficiency in adults: when to test and how to treat. Mayo Clin Proc 2010; 85(8): 752–7; quiz 757–8. doi: 10.4065/mcp.2010.0138.
  2. Vieth R, Bischoff-Ferrari H, Boucher BJ, Dawson-Hughes B, Garland CF, Heaney RP, et al. The urgent need to recommend an intake of vitamin D that is effective. Am J Clin Nutr 2007; 85(3): 649–50.
  3. Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357(3): 266–81. doi: 10.1056/NEJMra070553.
  4. Linos E, Keiser E, Kanzler M, Sainani KL, Lee W, Vittinghoff E, et al. Sun protective behaviors and vitamin D levels in the US population: NHANES 2003–2006. Cancer Causes Control 2012; 23(1): 133–40. doi: 10.1007/s10552-011-9862-0.
  5. Sicherer SH, Sampson HA. Food allergy: epidemiology, pathogenesis, diagnosis, and treatment. J Allergy Clin Immunol 2014; 133(2): 291–307; quiz 308. doi: 10.1016/j.jaci.2013.11.020.
  6. Camargo CA, Jr., Clark S, Kaplan MS, Lieberman P, Wood RA. Regional differences in EpiPen prescriptions in the United States: the potential role of vitamin D. J Allergy Clin Immunol 2007; 120(1): 131–6. doi: 10.1016/j.jaci.2007.03.049.
  7. Green TD, LaBelle VS, Steele PH, Kim EH, Lee LA, Mankad VS, et al. Clinical characteristics of peanut-allergic children: recent changes. Pediatrics 2007; 120(6): 1304–10. doi: 10.1542/peds.2007-0350.
  8. Sicherer SH, Furlong TJ, Munoz-Furlong A, Burks AW, Sampson HA. A voluntary registry for peanut and tree nut allergy: characteristics of the first 5149 registrants. J Allergy Clin Immunol 2001; 108(1): 128–32. doi: 10.1067/mai.2001.115755.
  9. Vassallo MF, Banerji A, Rudders SA, Clark S, Mullins RJ, Camargo CA Jr. Season of birth and food allergy in children. Ann Allergy Asthma Immunol 2010; 104(4): 307–13. doi: 10.1016/j.anai.2010.01.019.
  10. Matsui T, Tanaka K, Nakagawa T, Sasaki K, Nakata J, Sugiura S, et al. Sun exposure inversely related to food sensitization during infancy. Pediatr Allergy Immunol 2015; 26(7): 628–33. doi: 10.1111/pai.12445.
  11. Rudders SA, Espinola JA, Camargo CA Jr. North-south differences in US emergency department visits for acute allergic reactions. Ann Allergy Asthma Immunol 2010; 104(5): 413–16. doi: 10.1016/j.anai.2010.01.022.
  12. Sheehan WJ, Graham D, Ma L, Baxi S, Phipatanakul W. Higher incidence of pediatric anaphylaxis in northern areas of the United States. J Allergy Clin Immunol 2009; 124(4): 850–2 e2. doi: 10.1016/j.jaci.2009.06.044.
  13. Nwaru BI, Ahonen S, Kaila M, Erkkola M, Haapala AM, Kronberg-Kippila C, et al. Maternal diet during pregnancy and allergic sensitization in the offspring by 5 yrs of age: a prospective cohort study. Pediatr Allergy Immunol 2010; 21(1 Pt 1): 29–37. doi: 10.1111/j.1399-3038.2009.00949.x.
  14. Camargo CA Jr., Rifas-Shiman SL, Litonjua AA, Rich-­Edwards JW, Weiss ST, Gold DR, et al. Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. Am J Clin Nutr 2007; 85(3): 788–95.
  15. Yu LC. Intestinal epithelial barrier dysfunction in food hypersensitivity. J Allergy (Cairo) 2012; 2012: 596081. doi: 10.1155/2012/596081.
  16. Chen T, Liu X, Ma L, He W, Li W, Cao Y, et al. Food allergens affect the intestinal tight junction permeability in inducing intestinal food allergy in rats. Asian Pac J Allergy Immunol 2014; 32(4): 345–53. doi: 10.12932/AP0443.32.4.2014.
  17. Jeon MK, Klaus C, Kaemmerer E, Gassler N. Intestinal barrier: molecular pathways and modifiers. World J Gastrointest Pathophysiol 2013; 4(4): 94–9. doi: 10.4291/wjgp.v4.i4.94.
  18. Huang J, Zhong Y, Cai W, Zhang H, Tang W, Chen B. The effects of probiotics supplementation timing on an ovalbumin-sensitized rat model. FEMS Immunol Med Microbiol 2010; 60(2): 132–41. doi: 10.1111/j.1574-695X.2010.00727.x.
  19. Assa A, Vong L, Pinnell LJ, Avitzur N, Johnson-Henry KC, Sherman PM. Vitamin D deficiency promotes epithelial barrier dysfunction and intestinal inflammation. J Infect Dis. 2014; 210(8): 1296–305. doi: 10.1093/infdis/jiu235.
  20. Ooi JH, Chen J, Cantorna MT. Vitamin D regulation of immune function in the gut: why do T cells have vitamin D receptors? Mol Aspects Med 2012; 33(1): 77–82. doi: 10.1016/j.mam.2011.10.014.
  21. Chun RF, Liu PT, Modlin RL, Adams JS, Hewison M. Impact of vitamin D on immune function: lessons learned from genome-wide analysis. Front Physiol 2014; 5: 151. doi: 10.3389/fphys.2014.00151.
  22. Palomares O, Yaman G, Azkur AK, Akkoc T, Akdis M, Akdis CA. Role of Treg in immune regulation of allergic diseases. Eur J Immunol 2010; 40(5): 1232–40. doi: 10.1002/eji.200940045.
  23. Agrawal T, Gupta GK, Agrawal DK. Vitamin D deficiency decreases the expression of VDR and prohibitin in the lungs of mice with allergic airway inflammation. Exp Mol Pathol 2012; 93(1): 74–81. doi: 10.1016/j.yexmp.2012.04.004.
  24. Song DJ, Cho JY, Miller M, Strangman W, Zhang M, Varki A, et al. Anti-Siglec-F antibody inhibits oral egg allergen induced intestinal eosinophilic inflammation in a mouse model. Clin Immunol 2009; 131(1): 157–69. doi: 10.1016/j.clim.2008.11.009.
  25. Zhong Y, Huang J, Tang W, Chen B, Cai W. Effects of probiotics, probiotic DNA and the CpG oligodeoxynucleotides on ovalbumin-sensitized Brown-Norway rats via TLR9/NF-kappaB pathway. FEMS Immunol Med Microbiol 2012; 66(1): 71–82. doi: 10.1111/j.1574-695X.2012.00991.x.
  26. Ozkan KU, Ozokutan BH, Inanc F, Boran C, Kilinc M. Does maternal nicotine exposure during gestation increase the injury severity of small intestine in the newborn rats subjected to experimental necrotizing enterocolitis. J Pediatr Surg 2005; 40(3): 484–8. doi: 10.1016/j.jpedsurg.2004.11.040.
  27. Sampson HA, Burks AW. Mechanisms of food allergy. Annu Rev Nutr 1996; 16: 161–77. doi: 10.1146/
  28. Sharief S, Jariwala S, Kumar J, Muntner P, Melamed ML. Vitamin D levels and food and environmental allergies in the United States: results from the National Health and Nutrition Examination Survey 2005–2006. J Allergy Clin Immunol 2011; 127(5): 1195–202. doi: 10.1016/j.jaci.2011.01.017.
  29. Allen KJ, Koplin JJ, Ponsonby AL, Gurrin LC, Wake M, Vuillermin P, et al. Vitamin D insufficiency is associated with challenge-proven food allergy in infants. J Allergy Clin Immunol 2013; 131(4): 1109–16, 16 e1–6. doi: 10.1016/j.jaci.2013.01.017.
  30. Tolppanen AM, Williams D, Henderson J, Lawlor DA. Serum 25-hydroxy-vitamin D and ionised calcium in relation to lung function and allergen skin tests. Eur J Clin Nutr 2011; 65(4): 493–500. doi: 10.1038/ejcn.2011.6.
  31. Vasiliou JE, Lui S, Walker SA, Chohan V, Xystrakis E, Bush A, et al. Vitamin D deficiency induces Th2 skewing and eosinophilia in neonatal allergic airways disease. Allergy 2014; 69(10): 1380–9. doi: 10.1111/all.12465.
  32. Williams LM, Rudensky AY. Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3. Nat Immunol 2007; 8(3): 277–84. doi: 10.1038/ni1437.
  33. Wan YY, Flavell RA. Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression. Nature 2007; 445(7129): 766–70. doi: 10.1038/nature05479.
  34. Qamar N, Fishbein AB, Erickson KA, Cai M, Szychlinski C, Bryce PJ, et al. Naturally occurring tolerance acquisition to foods in previously allergic children is characterized by antigen specificity and associated with increased subsets of regulatory T cells. Clin Exp Allergy 2015; 45(11): 1663–72. doi: 10.1111/cea.12570.
  35. Syed A, Garcia MA, Lyu SC, Bucayu R, Kohli A, Ishida S, et al. Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3). J Allergy Clin Immunol 2014; 133(2): 500–10. doi: 10.1016/j.jaci.2013.12.1037.
  36. Kang SA, Park MK, Cho MK, Park SK, Jang MS, Yang BG, et al. Parasitic nematode-induced CD4+Foxp3+T cells can ameliorate allergic airway inflammation. PLoS Negl Trop Dis 2014; 8(12): e3410. doi: 10.1371/journal.pntd.0003410.
  37. Bogdanou D, Penna-Martinez M, Filmann N, Chung TL, Moran-Auth Y, Wehrle J, et al. T lymphocyte and glycemic status after vitamin D treatment in type 1 diabetes: a randomized controlled trial with sequential cross-over. Diabetes Metab Res Rev 2017; 33(3): e2865. doi: 10.1002/dmrr.2865. PubMed PMID: 27764529.
  38. Garrido-Urbani S, Bradfield PF, Imhof BA. Tight junction dynamics: the role of junctional adhesion molecules (JAMs). Cell Tissue Res 2014; 355(3): 701–15. doi: 10.1007/s00441-014-1820-1.
  39. Steed E, Balda MS, Matter K. Dynamics and functions of tight junctions. Trends Cell Biol 2010; 20(3): 142–9. doi: 10.1016/j.tcb.2009.12.002.
  40. Dejana E, Tournier-Lasserve E, Weinstein BM. The control of vascular integrity by endothelial cell junctions: molecular basis and pathological implications. Dev Cell 2009; 16(2): 209–21. doi: 10.1016/j.devcel.2009.01.004.
  41. Catalioto RM, Maggi CA, Giuliani S. Intestinal epithelial barrier dysfunction in disease and possible therapeutical interventions. Curr Med Chem 2011; 18(3): 398–426.
  42. Pizzuti D, Senzolo M, Buda A, Chiarelli S, Giacomelli L, Mazzon E, et al. In vitro model for IgE mediated food allergy. Scand J Gastroenterol 2011; 46(2): 177–87. doi: 10.3109/00365521.2010.525716.
How to Cite
Wu J., Zhong Y., Shen X., Yang K., & Cai W. (2018). Maternal and early-life vitamin D deficiency enhances allergic reaction in an ovalbumin-sensitized BALB/c mouse model. Food & Nutrition Research, 62.
Original Articles

Most read articles by the same author(s)