The following peer-reviewed papers support the findings of the original work by Wakefield and colleagues at the Royal Free Hospital in the UK:
1) Furlano R, Anthony A, Day R, Brown A, Mc Garvey L, Thomson M, et al. Colonic CD8 and T cell filtration with epithelial damage in children with autism. J Pediatr 2001;138:366-72.
2) Torrente F., Machado N., Perez-Machado M., Furlano R., Thomson M., Davies S., Wakefield AJ, Walker-Smith JA, Murch SH. Enteropathy with T cell infiltration and epithelial IgG deposition in autism. Molecular Psychiatry. 2002;7:375-382.
3) Ashwood P, Murch SH, Anthony A, Hayes C, Machado MP, Torrente F, Thomson MA, Heuschkel R, Wakefield AJ., Mucosal and peripheral blood lymphocyte cytokine profiles in children with regressive autism and gastrointestinal symptoms: Mucosal immune activation and reduced counter regulatory interleukin-10. Gastroenterol. 2002;122 (Suppl):A617
4) 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(6):664-73.
5) Wakefield AJ., Puleston J. Montgomery SM., Anthony A., O’Leary J.J., Murch SH Entero-colonic encephalopathy, autism and opioid receptor ligands. Alimentary Pharmacology & Therapeutics. 2002;16:663-674
6) Wakefield AJ. The Gut-Brain Axis in Childhood developmental Disorders. Journal of Pediatric Gastroenterology and Nutrition. 2002;34:S14-S17
7) Uhlmann V, Martin CM, Sheils O, Pilkington L, Silva I, Killalea A, Murch SH, Wakefield AJ, O’Leary JJ., Potential viral pathogenic mechanism for new variant inflammatory bowel disease. Molecular Pathology 2002;55:84-90
8) Ashwood P, Anthony A, Pellicer AA, Torrente F, Wakefield AJ. Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathology. Journal of Clinical Immunology, 2003;23:504-517.
9) Torrente F, Anthony A, Heuschkel RB, Thomson MA, Ashwood P, Murch SH. Focal-enhanced gastritis in regressive autism with features distinct from Crohn's and Helicobacter pylori gastritis. Am J Gastroenterol. 2004;99:598-605
10) 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(1-2):126-34.
11) 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 Aug;17(8):827-36.
The following two peer-reviewed papers from the Royal Free Hospital in the UK were withdrawn for political reasons, but the science remains valid and relevant
1) Wakefield AJ, Murch SM, Anthony A et al., Ileal- lymphoid- nodular Hyperplasia, Non- specific Colitis, and Pervasive Developmental Disorder in Children, The Lancet, 1998, 351(9103): 637– 41.
2) Wakefield AJ, Anthony A, Murch SH, Thomson M, Montgomery SM, Davies S, Walker-Smith JA. Enterocolitis in children with developmental disorder. American Journal of Gastroenterology 2000;95:2285-2295.
The following peer-reviewed papers duplicate Dr. Wakefield’s original findings in five additional countries, including the US, Italy, Venezuela, Canada and Poland:
1) Gonzalez, L. et al., Endoscopic and Histological Characteristics of the Digestive Mucosa in Autistic Children with gastro-Intestinal Symptoms. Arch Venez Pueric Pediatr, 2005;69:19-25.
2) Balzola, F., et al., Panenteric IBD-like disease in a patient with regressive autism shown for the first time by wireless capsule enteroscopy: Another piece in the jig-saw of the gut-brain syndrome? American Journal of Gastroenterology, 2005. 100(4): p. 979- 981.
3) Balzola F et al . Autistic enterocolitis: confirmation of a new inflammatory bowel disease in an Italian cohort of patients. Gastroenterology 2005;128(Suppl. 2);A-303.
4) Krigsman A, Boris M, Goldblatt A, Stott C. Clinical Presentation and Histologic Findings at Ileocolonoscopy in Children with Autistic Spectrum Disorder and Chronic Gastrointestinal Symptoms. Autism Insights. 2009;1:1–11.
5) Horvath K., Papadimitriou J.C., Rabsztyn A., Drachenberg C., Tildon J.T. 1999. Gastrointestinal abnormalities in children with autism. J. Pediatrics 135: 559-563.
6) Sabra S, Bellanti JA, Colon AR. Ileal lymphoid hyperplasia, non-specific colitis and pervasive developmental disorder in children. The Lancet 1998;352:234-5.
7) Sabra A, Hartman D, Zeligs BJ et al., Linkage of ileal-lymphoid-nodular hyperplasia (ILNH), food allergy and CNS developmental abnormalities: evidence for a non-IgE association, Ann Allergy Asthma Immunol, 1999;82:8
8) Galiatsatos P, Gologan A, Lamoureux E, Autistic enterocolitis: Fact or fiction? Can J Gastroenterol. 2009:23:95-98
9) Jarocka-Cyrta et al. Brief report: eosinophilic esophagitis as a cause of feeding problems in an autistic boy. The first reported case.J. Aut. Dev. Disord. Online July 10, 2010
The following articles support the importance of recognizing and treating gastrointestinal symptoms in autistic children:
1) Buie T, et al. Pediatrics. 2010 Jan;125 Suppl 1:S19-29. Recommendations for evaluation and treatment of common gastrointestinal problems in children with ASDs.
2) Buie T, et al. Pediatrics. 2010 Jan;125 Suppl 1:S1-18. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report.
The following peer-reviewed papers provide further support for gastrointestinal disturbances involving the immune system in autism.
1) Jyonouchi H., Sun S., Lee H. 2001. Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression. J. Neuroimmunol. 120(1-2):170-9
2) Jyonouchi H, Geng L, Ruby A, Zimmerman-Bier B. Dysregulated Innate Immune Responses in Young Children with Autism Spectrum Disorders: Their Relationship to Gastrointestinal Symptoms and Dietary Intervention. Neuropsychobiology. 2005;28:5177-85
3) Jyonouchi H, Geng L, Ruby A, Reddy C, Zimmerman-Bier B. Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in children with autism spectrum disorders. J Pediatr.2005;146(5):605-10.
4) Jyonouchi H, Sun S, Itokazu N. Innate immunity associated with inflammatory responses and cytokine production against common dietary proteins in patients with autism spectrum disorder. Neuropsychobiology. 2002;46(2):76-84.
5) Vojdani A, O'Bryan T, Green JA, McCandless J, Woeller KN, Vojdani E, Nourian AA, Cooper EL. Immune response to dietary proteins, gliadin and cerebellar peptides in children with autism. Nutr. Neurosci. 2004;7:151-61.
6) Whiteley P, Haracopos D, Knivsberg AM, Reichelt KL, Parlar S, Jacobsen J, Seim A, Pedersen L, Schondel M, Shattock P. The ScanBrit randomised, controlled, single-blind study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders. Nutr Neurosci. 2010;13(2):87-100.
7) Knivsberg AM, Reichelt KL, Høien T, Nødland M. A randomised, controlled study of dietary intervention in autistic syndromes. Nutr Neurosci. 2002;5(4):251-61.
8) Balzola F, et al. Beneficial behavioural effects of IBD therapy and gluten/casein-free diet in an Italian cohort of patients with autistic enterocolitis followed over one year. Gastroenterology 2008;4:S1364.
9) Valicenti-McDermott M., McVicar K., Rapin I., et al., Frequency of Gastrointestinal Symptoms in Children with Autistic Spectrum Disorders and Association with Family History of Autoimmune Disease. Developmental and Behavioral Pediatrics. 2006;27:128-136
10) Chen B, Girgis S, El-Matary W. Childhood Autism and Eosinophilic Colitis. Digestion 2010;18:127-129
11) Sandler R, Finegold SM., Bolte ER., et al. Short-term benefit from oral vancomycin treatment of regressive-onset autism. J Child Neurol. 2000;15:429-435
Dr Andrew Wakefield - Autism/Gut Connection