Skip to main content

Food allergy and autism spectrum disorders: Is there a link?

Abstract

Gastrointestinal (GI) symptoms are common comorbidities in children with autism spectrum disorders (ASDs). Parents often attribute these GI symptoms to food allergy (FA), although an evaluation for IgE-mediated FA is often unrevealing. Our previous studies indicated a high prevalence of non-IgE-mediated FA in young children with ASDs. Therefore, non-IgE-mediated FA may account for some but not all GI symptoms observed in children with ASDs. This raises the question of what treatment measures are applicable to ASD children with GI symptoms. A wide variety of dietary supplements and dietary intervention measures for ASD children have been promoted by medical professionals practicing complementary and alternative medicine despite the lack of rigorous scientific validation in most instances. This review summarizes possible (or proposed) etiologies of GI symptoms in ASD children and discusses risks and possible benefits of intervention measures promoted by complementary and alternative practitioners, with emphasis on FA.

This is a preview of subscription content, access via your institution.

References and Recommended Reading

  1. Hertz-Picciotto I, Croen LA, Hansen R, et al.: The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism. Environ Health Perspect 2006, 114:1119–1125.

    PubMed  Article  Google Scholar 

  2. Abrahams BS, Geschwind DH: Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet 2008, 9:341–355.

    PubMed  Article  CAS  Google Scholar 

  3. Lainhart JE, Ozonoff S, Coon H, et al.: Autism, regression, and the broader autism phenotype. Am J Med Genet 2002, 113:231–237.

    PubMed  Article  Google Scholar 

  4. Horvath K, Perman JA: Autism and gastrointestinal symptoms. Curr Gastroenterol Rep 2002, 4:251–258.

    PubMed  Article  Google Scholar 

  5. Porter EM, Bevins CL, Ghosh D, Ganz T: The multifaceted Paneth cell. Cell Mol Life Sci 2002, 59:156–170.

    PubMed  Article  CAS  Google Scholar 

  6. Lee J, Gonzales-Navajas JM, Raz E: The “polarizing-tolerizing” mechanism of intestinal epithelium: its relevance to colonic homeostasis. Semin Immunopathol 2008, 30:3–9.

    PubMed  Article  Google Scholar 

  7. Lee J, Mo JH, Shen C, et al.: Toll-like receptor signaling in intestinal epithelial cells contributes to colonic homoeostasis. Curr Opin Gastroenterol 2007, 23:27–31.

    PubMed  CAS  Article  Google Scholar 

  8. White JF: Intestinal pathophysiology in autism. Exp Biol Med (Maywood) 2003, 228:639–649.

    CAS  Google Scholar 

  9. D’Eufemia P, Celli M, Finocchiaro R, et al.: Abnormal intestinal permeability in children with autism. Acta Paediatr 1996, 85:1076–1079.

    PubMed  Article  Google Scholar 

  10. Horvath K, Collins RM, Rabsztyn A, et al.: Secretin improves intestinal permeability in autistic children [abstract]. J Pediatr Gastroenterol Nutr 2000, S31:31.

    Google Scholar 

  11. Robertson MA, Sigalet DL, Holst JJ, et al.: Intestinal permeability and glucagon-like peptide-2 in children with autism: a controlled pilot study. J Autism Dev Disord 2008, 38:1066–1071.

    PubMed  Article  Google Scholar 

  12. Dupont C, Heyman M: Food protein-induced enterocolitis syndrome: laboratory perspectives. J Pediatr Gastroenterol Nutr 2000, 30(Suppl):S50–S57.

    PubMed  Article  Google Scholar 

  13. Heyman M: Gut barrier dysfunction in food allergy. Eur J Gastroenterol Hepatol 2005, 17:1279–1285.

    PubMed  Article  Google Scholar 

  14. Ventura MT, Polimeno L, Amoruso AC, et al.: Intestinal permeability in patients with adverse reactions to food. Dig Liver Dis 2006, 38:732–736.

    PubMed  Article  CAS  Google Scholar 

  15. Chin AC, Lee WY, Nusrat A, et al.: Neutrophil-mediated activation of epithelial protease-activated receptors-1 and -2 regulates barrier function and transepithelial migration. J Immunol 2008, 181:5702–5710.

    PubMed  CAS  Google Scholar 

  16. Magalhaes JG, Tattoli I, Girardin SE: The intestinal epithelial barrier: how to distinguish between the microbial flora and pathogens. Semin Immunol 2007, 19:106–115.

    PubMed  Article  CAS  Google Scholar 

  17. Rescigno M, Urbano M, Valzasina B, et al.: Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2001, 2:361–367.

    PubMed  Article  CAS  Google Scholar 

  18. Chehade M, Mayer L: Oral tolerance and its relation to food hypersensitivities. J Allergy Clin Immunol 2005, 115:3–12; quiz 13.

    PubMed  Article  Google Scholar 

  19. Man AL, Lodi F, Bertelli E, et al.: Macrophage migration inhibitory factor plays a role in the regulation of microfold (M) cell-mediated transport in the gut. J Immunol 2008, 181:5673–5680.

    PubMed  CAS  Google Scholar 

  20. Mucida D, Park Y, Kim G, et al.: Reciprocal Th17 and regulatory T cell differentiation mediated by retinoic acid. Science 2007, 317:256–260.

    PubMed  Article  CAS  Google Scholar 

  21. Sun CM, Hall JA, Blank RB, et al.: Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J Exp Med 2007, 204:1775–1785.

    PubMed  Article  CAS  Google Scholar 

  22. Coombes JL, Siddiqui KR, Arancibia-Carcamo CV, et al.: A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J Exp Med 2007, 204:1757–1764.

    PubMed  Article  CAS  Google Scholar 

  23. Burks AW, Laubach S, Jones SM: Oral tolerance, food allergy, and immunotherapy: implications for future treatment. J Allergy Clin Immunol 2008, 121:1344–1350.

    PubMed  Article  CAS  Google Scholar 

  24. Kelly D, Campbell JI, King TP, et al.: Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclearcytoplasmic shuttling of PPAR-gamma and RelA. Nat Immunol 2004, 5:104–112.

    PubMed  Article  CAS  Google Scholar 

  25. Sandler RH, Finegold SM, Bolte ER, et al.: Short-term benefit from oral vancomycin treatment of regressive-onset autism. J Child Neurol 2000, 15:429–435.

    PubMed  Article  CAS  Google Scholar 

  26. Finegold SM, Molitoris D, Song Y, et al.: Gastrointestinal microflora studies in late-onset autism. Clin Infect Dis 2002, 35:S6–S16.

    PubMed  Article  Google Scholar 

  27. Parracho HM, Bingham MO, Gibson GR, McCartney AL: Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol 2005, 54:987–991.

    PubMed  Article  Google Scholar 

  28. Shultz SR, MacFabe DF, Ossenkopp KP, et al.: Intracerebroventricular injection of propionic acid, an enteric bacterial metabolic end-product, impairs social behavior in the rat: implications for an animal model of autism. Neuropharmacology 2008, 54:901–911.

    PubMed  Article  CAS  Google Scholar 

  29. MacFabe DF, Cain DP, Rodriguez-Capote K, et al.: Neurobiological effects of intraventricular propionic acid in rats: possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders. Behav Brain Res 2007, 176:149–169.

    PubMed  Article  CAS  Google Scholar 

  30. Furlano RI, Anthony A, Day R, et al.: Colonic CD8 and gamma delta T-cell infiltration with epithelial damage in children with autism. J Pediatr 2001, 138:366–372.

    PubMed  Article  CAS  Google Scholar 

  31. Wakefield AJ, Anthony A, Murch SH, et al.: Enterocolitis in children with developmental disorders. Am J Gastroenterol 2000, 95:2285–2295.

    PubMed  Article  CAS  Google Scholar 

  32. Wakefield AJ, Ashwood P, Limb K, Anthony A: The significance of ileo-colonic lymphoid nodular hyperplasia in children with autistic spectrum disorder. Eur J Gastroenterol Hepatol 2005, 17:827–836.

    PubMed  Article  Google Scholar 

  33. Ashwood P, Anthony A, Pellicer AA, et al.: Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathology. J Clin Immunol 2003, 23:504–517.

    PubMed  Article  Google Scholar 

  34. Torrente F, Ashwood P, Day R, et al.: Small intestinal enteropathy with epithelial IgG and complement deposition in children with regressive autism. Mol Psychiatry 2002, 7:375–382, 334.

    PubMed  Article  CAS  Google Scholar 

  35. Ashwood P, Wakefield AJ: Immune activation of peripheral blood and mucosal CD3+ lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms. J Neuroimmunol 2006, 173:126–134.

    PubMed  Article  CAS  Google Scholar 

  36. Ashwood P, Anthony A, Torrente F, Wakefield AJ: Spontaneous mucosal lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms: mucosal immune activation and reduced counter regulatory interleukin-10. J Clin Immunol 2004, 24:664–673.

    PubMed  Article  CAS  Google Scholar 

  37. DeFelice ML, Ruchelli ED, Markowitz JE, et al.: Intestinal cytokines in children with pervasive developmental disorders. Am J Gastroenterol 2003, 98:1777–1782.

    PubMed  Article  CAS  Google Scholar 

  38. Lala S, Ogura Y, Osborne C, et al.: Crohn’s disease and the NOD2 gene: a role for Paneth cells. Gastroenterology 2003, 125:47–57.

    PubMed  Article  CAS  Google Scholar 

  39. Cho JH: The genetics and immunopathogenesis of inflammatory bowel disease. Nat Rev Immunol 2008, 8:458–466.

    PubMed  Article  CAS  Google Scholar 

  40. Vargas DL, Nascimbene C, Krishnan C, et al.: Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 2005, 57:67–81.

    PubMed  Article  CAS  Google Scholar 

  41. Pardo CA, Vargas DL, Zimmerman AW: Immunity, neuroglia and neuroinflammation in autism. Int Rev Psychiatry 2005, 17:485–495.

    PubMed  Article  Google Scholar 

  42. Zimmerman AW, Jyonouchi H, Comi AM, et al.: Cerebrospinal fluid and serum markers of inflammation in autism. Pediatr Neurol 2005, 33:195–201.

    PubMed  Article  Google Scholar 

  43. Pardo CA, Eberhart CG: The neurobiology of autism. Brain Pathol 2007, 17:434–447.

    PubMed  Article  CAS  Google Scholar 

  44. Ashwood P, Kwong C, Hansen R, et al.: Brief report: plasma leptin levels are elevated in autism: association with early onset phenotype? J Autism Dev Disord 2008, 38:169–175.

    PubMed  Article  Google Scholar 

  45. Chauhan A, Chauhan V, Brown WT, Cohen I: Oxidative stress in autism: increased lipid peroxidation and reduced serum levels of ceruloplasmin and transferrin—the antioxidant proteins. Life Sci 2004, 75:2539–2549.

    PubMed  Article  CAS  Google Scholar 

  46. Deth R, Muratore C, Benzecry J, et al.: How environmental and genetic factors combine to cause autism: a redox/methylation hypothesis. Neurotoxicology 2008, 29:190–201.

    PubMed  Article  CAS  Google Scholar 

  47. James SJ, Melnyk S, Jernigan S, et al.: Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet 2006, 141B:947–956.

    PubMed  Article  CAS  Google Scholar 

  48. Martin-Ruiz CM, Lee M, Perry RH, et al.: Molecular analysis of nicotinic receptor expression in autism. Brain Res Mol Brain Res 2004, 123:81–90.

    PubMed  Article  CAS  Google Scholar 

  49. Ashley-Koch AE, Mei H, Jaworski J, et al.: An analysis paradigm for investigating multi-locus effects in complex disease: examination of three GABA receptor subunit genes on 15q11-q13 as risk factors for autistic disorder. Ann Hum Genet 2006, 70:281–292.

    PubMed  Article  CAS  Google Scholar 

  50. Vincent JB, Horike SI, Choufani S, et al.: An inversion inv(4)(p12–p15.3) in autistic siblings implicates the 4p GABA receptor gene cluster. J Med Genet 2006, 43:429–434.

    PubMed  Article  CAS  Google Scholar 

  51. Thompson WW, Price C, Goodson B, et al.: Early thimerosal exposure and neuropsychological outcomes at 7 to 10 years. N Engl J Med 2007, 357:1281–1292.

    PubMed  Article  CAS  Google Scholar 

  52. Silva MF, Aires CC, Luis PB, et al.: Valproic acid metabolism and its effects on mitochondrial fatty acid oxidation: a review. J Inherit Metab Dis 2008 Apr 4 (Epub ahead of print).

  53. Gupta S, Aggarwal S, Rashanravan B, Lee T: Th1- and Th2-like cytokines in CD4+ and CD8+ T cells in autism. J Neuroimmunol 1998, 85:106–109.

    PubMed  Article  CAS  Google Scholar 

  54. Molloy CA, Morrow AL, Meinzen-Derr J, et al.: Elevated cytokine levels in children with autism spectrum disorder. J Neuroimmunol 2006, 172:198–205.

    PubMed  Article  CAS  Google Scholar 

  55. Bakkaloglu B, Anlar B, Anlar FY, et al.: Atopic features in early childhood autism. Eur J Paediatr Neurol 2008, 12:476–479.

    PubMed  Article  Google Scholar 

  56. Karlsson MR, Rugtveit J, Brandtzaeg P: Allergen-responsive CD4+CD25+ regulatory T cells in children who have outgrown cow’s milk allergy. J Exp Med 2004, 199:1679–1688.

    PubMed  Article  CAS  Google Scholar 

  57. Jyonouchi H, Geng L, Ruby A, et al.: Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in children with autism spectrum disorders. J Pediatr 2005, 146:605–610.

    PubMed  Article  CAS  Google Scholar 

  58. Hwang JB, Sohn SM, Kim AS: Prospective follow up-oral food challenge in food protein-induced enterocolitis syndrome. Arch Dis Child 2008 Oct 1 (Epub ahead of print).

  59. Horwitz DA, Zheng SG, Gray JD: Natural and TGF-betainduced Foxp3(+)CD4(+) CD25(+) regulatory T cells are not mirror images of each other. Trends Immunol 2008, 29:429–435.

    PubMed  Article  CAS  Google Scholar 

  60. Christison GW, Ivany K: Elimination diets in autism spectrum disorders: any wheat amidst the chaff? J Dev Behav Pediatr 2006, 27:S162–S171.

    PubMed  Article  Google Scholar 

  61. Knivsberg AM, Reichelt KL, Hoien T, Nodland M: A randomised, controlled study of dietary intervention in autistic syndromes. Nutr Neurosci 2002, 5:251–261.

    PubMed  Article  CAS  Google Scholar 

  62. Elder JH, Shankar M, Shuster J, et al.: The gluten-free, casein-free diet in autism: results of a preliminary double blind clinical trial. J Autism Dev Disord 2006, 36:413–420.

    PubMed  Article  Google Scholar 

  63. Cornish E: Gluten and casein free diets in autism: a study of the effects on food choice and nutrition. J Hum Nutr Diet 2002, 15:261–269.

    PubMed  Article  CAS  Google Scholar 

  64. Bolman WM, Richmond JA: A double-blind, placebo-controlled, crossover pilot trial of low dose dimethylglycine in patients with autistic disorder. J Autism Dev Disord 1999, 29:191–194.

    PubMed  Article  CAS  Google Scholar 

  65. Kern JK, Miller VS, Cauller PL, et al.: Effectiveness of N,Ndimethylglycine in autism and pervasive developmental disorder. J Child Neurol 2001, 16:169–173.

    PubMed  CAS  Google Scholar 

  66. Chapman TM, Plosker GL, Figgitt DP: VSL#3 probiotic mixture: a review of its use in chronic inflammatory bowel diseases. Drugs 2006, 66:1371–1387.

    PubMed  Article  CAS  Google Scholar 

  67. Isolauri E, Salminen S: Probiotics: use in allergic disorders: a Nutrition, Allergy, Mucosal Immunology, and Intestinal Microbiota (NAMI) Research Group Report. J Clin Gastroenterol 2008, 42(Suppl 2):S91–S96.

    Article  Google Scholar 

  68. Savilahti E, Kuitunen M, Vaarala O: Pre and probiotics in the prevention and treatment of food allergy. Curr Opin Allergy Clin Immunol 2008, 8:243–248.

    PubMed  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Harumi Jyonouchi.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Jyonouchi, H. Food allergy and autism spectrum disorders: Is there a link?. Curr Allergy Asthma Rep 9, 194–201 (2009). https://doi.org/10.1007/s11882-009-0029-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11882-009-0029-y

Keywords

  • Autism Spectrum Disorder
  • Autism Spectrum Disorder
  • Food Allergy
  • Allergy Clin Immunol
  • Autistic Child