Autism and the gut:
By Zurama
04-27-08
Autism and the gut:
The research is so thorough now, that it conclusively proves a new form of inflammatory bowel disease / enterocolitis as the cause of autism:
The possible association between MMR vaccine, regressive autism and intestinal symptoms was first recounted by parents to Dr. Andrew Wakefield, a UK gastroenterologist at the Royal Free Hospital, London, in 1995. The first group of children presenting in this way to Wakefield and colleagues at the Royal Free were reported in The Lancet as a clinical case series in February 1998 (1). Although the interpretation put on this paper at the time was the subject of intense controversy - particularly in the absence of corroborative clinical research by other researchers at that time - the strong evidence of a hitherto-unreported link between autism and a novel intestinal disease, ileal-lymphoid nodular hyperplasia, has not been disputed, and still stands as an important initial clue as to the causes of regressive autism.
• A group of researchers led by Horvath (2) subsequently independently reported in 1999 upon patients with autism who had gastrointestinal symptoms, including a study of 36 children with autism that found grade I or II reflux esophagitis in 25 (69.4%), chronic gastritis in 15 (42%) and chronic duodenitis in 24 (67%).
Further research published in September 2000 (3) by Wakefield, Anthony et al confirmed that ileal-lymphoid nodular hyperplasia (ILNH) was found in 54 out of 58 (93%) children with autism or other disorders (50 with autism, 5 Aspergers, 2 disintegrative disorder, one ADHD, one schizophrenia, one dyslexia), but only 5 out of 35 (14.3%) normal controls, pointing to a very strong ILNH-autism link.
• Research published in 2001 by Furlano, Anthony et al (4) reported on ileocolonoscopy performed on 21 consecutively-evaluated children with autistic spectrum disorders and bowel symptoms, and made “blinded” comparisons with 8 children who had a histologically normal ileum and colon, plus 10 developmentally-normal children with ILNH, 15 with Crohn’s Disease, and 14 with ulcerative colitis. The study confirmed a distinct lymphocytic colitis in the children with ASD, in which the epithelium appeared particularly affected, offering further corroboration for gut epithelial dysfunction in autism.
• Research reported in 2001 by Buie (5) reported that, as a result of over 400 gastrointestinal endoscopies with biopsies and evaluation of digestive enzyme function, on children with autism, he had found the presence of chronic inflammation of the intestinal tract, although the incidence was less frequent than in the Royal Free Hospital group of patients reported by Wakefield et al, and that biopsy results indicated the presence of chronic inflammation of the digestive tracts, including esophagitis, gastritis and enterocolitis. Ileal lymphoid nodular hyperplasia, as first found by the Royal Free study, had been found in 15 of 89 children examined for it.
• A review (6) published in September 2002 by Wakefield, Anthony, Montgomery et al noted that as early as 1986, a researcher named Soddy had noted that recurrent gastrointestinal upsets were a constant feature of autistic children, and that in a systematic analysis of an unselected population of 385 children on the autistic spectrum, clinically-significant gastrointestinal symptoms occurred in 46%, compared with 10% of 97 developmentally-normal controls, strongly suggesting a gastrointestinal-autism link. Mucosal lesions in the small and large intestine were consistent with an autoimmune pathology, and suggested the possibility of an autoimmune response leading to cerebral damage.
• A June 2002 presentation (7) by Krigsman to the US Congressional Committee on Government Reform reported that a large percentage of his autistic patients suffered from chronic unexplained gastrointestinal symptoms. Of 43 patients, the majority had a clear history of developmental regression, after previous normal development, suffering gradual or precipitous decline between age 12 months and 18 months. Most regressive children also exhibited poor growth. Patients had undergone colonoscopy. Findings were that the lymphoid nodules of the terminal ileum were markedly enlarged, thus confirming the early work of the Royal Free team. Evaluation of biopsy specimens confirmed that 65% had colitis, 51% had active colitis, 40% had chronic colitis, 7% had eosinophilic colitis, 90% had lymphoid nodular hyperplasia of the terminal ileum, and 35% had neither active nor chronic nor eosinophilic colitis. Patterns of inflammation were patchy and unpredictable, but findings were similar and consistent from patient to patient within affected sub-groups.
• A November 2003 paper (8) published by Ashwood, Murch et al reported on the examination of 52 affected autistic children, compared with 25 histologically-normal developmentally-normal controls and a further 54 histologically-inflamed but developmentally-normal controls. Analysis of intestinal biopsies in regressive-autistic children indicated a novel lymphocytic enterocolitis with autoimmune features, though the precise linkage between the finding and cognitive functions still remained unclear. The study concluded that it provided further evidence of a pan-enteric mucosal immunopathology in children with regressive autism, that is distinct from other previously-known inflammatory bowel diseases.
• An April 2004 paper (9) by Torrente, Anthony et al identified, following earlier reports of lymphocytic colitis and small bowel enteropathy in children with regressive autism, that the gastritis in regressive autism was clearly distinct from that in Crohn’s and other conditions, pointing to a distinctive form of gastritis being linked with regressive autism.
• A November 2004 paper (10) by Ashwood, Anthony et al found that molecules (cytokines) produced by immune cells in the intestine, that cause or control inflammation, showed an abnormal pattern in autistic children compared with non-autistic children. The pattern was different to other forms of intestinal inflammation, and the disease resembled a longstanding viral disease of the intestine, not unlike the intestinal inflammation seen on patients with other viral infections such as HIV-associated enteropathy (intestinal disease) that often accompanies infection with HIV.
• A February 2005 paper (11) by Jyonouchi, Geng et al further confirmed the original ileal-lymphoid nodular hyperplasia/regressive autism link first reported by the Wakefield team in 1998. The study again found evidence of marked inflammatory and immune abnormalities in children with autism associated with gastrointestinal symptoms.
• An April 2005 published letter (12) by Balzola, Barbon et al, Pan-Enteric IBD-Like Disease in a Patient with Regressive Autism Shown for the First Time by the Wireless Capsule Enteroscopy - Another Piece in the Jigsaw of this Gut/Brain Syndrome?, reported that a 28-year-old male with regressive autism, severe constipation, bloating, abdomen distension and symptoms of gastroesophageal reflux was examined. Gastroscopy under general anaesthesia revealed hemorrhagic gastritis with inflammatory pseudopolypsthat had reached the pylorum, with a pearl-necklace appearance, and a panenteric IBD-like disease consistent with previously-published descriptions of autistic enterocolitis was finally diagnosed. The wireless capsule images were the first to be obtained beyond the limits of the duodenum and terminal ileum, and demonstrated the potential for the entire bowel to be implicated in this inflammatory disease.
• A May 2005 study (13) by Balzola, Daniela et al reported on 9 consecutive patients (range 7-30 years) with autism and chronic intestinal symptoms (abdominal pain, bloating, constipation and/or diahorrea). Routine blood and stool tests and gastroscopy and colonoscopy with multiple biopsies were performed under sedation, and wireless enteroscopy capsules were used in three of the adult patients. Gastroscopy revealed mucosal gastritis in 4 patients, esophagitis in 1 patient and duodenitis in 1 patient, and histological findings showed chronic inflammation of the stomach and duodenum in 6 patients, inconsistent with celiac disease. The authors reported that preliminary findings were strongly consistent with previous descriptions of autistic enterocolitis, and supported a not-coincidental occurrence. They showed for the first time a small-intestinal involvement, suggesting a pan-enteric localization of this new inflammatory bowel disease.
• Also in 2005, a further paper (14) by Wakefield, Ashwood et al was published, assessing ileocolonic lymphoid nodular hyperplasia in ASD and normal control children. Some 148 consecutive children with ASD, with gastrointestinal symptoms, were investigated by ileocolonoscopy, with 74 ASD children and 23 normal controls undergoing upper gastrointestinal endoscopy. The presence of lymphoid nodular hyperplasia was significantly greater in ASD children compared with controls, in the ileum (129 out of 144, compared with 8 out of 27 controls), and in the colon (88 out of 148, compared with 7 out of 30 controls). Comparative percentages were 90% vs 30% and 59% vs 23%. This was whether or not controls had co-existent colonic inflammation. The severity of ILNH was significantly greater in ASD children compared with controls, with moderate-to-severe ILNH present in 98 out of 144 ASD children compared with 4 out of 27 controls; percentages were 68% and 15%. On histopathological examination, hyperplasic lymphoid follicles were significantly more prevalent in the ileum of ASD children (84 out of 138, or 61%) compared with normal controls (2 out of 23, or 9%). The data thus further corroborated the finding that ileal lymphoid nodular hyperplasia is a significant pathological finding in autistic children.
• Additionally in 2005, a study (15) was published by Gonzalez, Lopez et al, seeking evidence of immunological alterations in 68 autistic children ages 22 months to 11 years and presenting with digestive systems, and examining biopsies from their digestive tracts. Endoscopies and colosopies were undertaken, with biopsies of the esophagus, stomach, duodenum and colon, with verification of presence of inflammation, eosiophil infiltration, lymphoid nodular hyperplasia and CD-4 and CD-8 cells. The results were that lymphoid nodular hyperplasia was discovered in 2/68 esophagus, 6/68 stomachs, 8/68 duodenums and 36/68 (53%) of colons. Eosiophil infiltration with more than 20 eosiphils per field were found in 3/68 eosphagus, 1/68 stomach, 8/68 duodenum and 24/68 (35%) colons. Inflammatory reactions were found in 56/68 (82%) esophogitis, 64/68 (94%) gastritis, and all (100%) presented with duodenitis and colitis. CD-4/CD-8 relationship existed of >3 in 42/68 (62%) and <1 in 16/68. The authors concluded that the children presented immunological and immunohistochemical alterations of the biopsies of their digestive tracts, and that there was a significant finding of lymphoid nodular hyperplasia, eosiophilinfiltration, and that prevalence of greater CD-4 than CD-8 cells in the inflammation of the intestinal wall demonstrated in favour of a Th2 type allergic reaction.
* 1) Wakefield et al, Inflammatory Bowel Disease Study Group, Royal Free Hospital London, Ileal Lymphoid Nodular Hyperplasia, Non Specific Colitis and Pervasive Development Disorder in Children, Lancet, 28th February 1998
(2) Horvath, Papadimitiou et al, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Gastrointestinal Abnormalities in Children With Autistic Disorder, Journal of Pediatrics, 1999 November, Vol 135 (5), pp559-563
(3) Wakefield, Anthony et al, Enterocolitis in Children with Developmental Disorders, American Journal of Gastroenterology, Sept 2000, Vol 95, No. 9, pp2285-2295
(4) Furlano, Anthony et al, Colonic CD8 and T-Cell Infiltration With Epithelial Damage in Children with Autism, Journal of Pediatrics, 2001; 138; No. 3, 366-372
(5) Paper by Dr. Timothy Buie, Harvard Massachusetts General Hospital, presented to the Oasis 2001 Conference for Autism, Portland, Oregon, November 2001
(6) Wakefield, Anthony, Montgomery et al, Inflammatory Bowel disease Study Group, Royal Free Hospital, University College Medical School, London, and Coombe Women’s Hospital and Trinity College Dublin, The Concept of Enterocolonic Encepalopathy, Autism and Opioid Receptor Ligands, Aliment Pharmacological Ther, 16: pp663-674
(7) Presentation by Krigsman to the US Congressional Committee on Government Reform’s June 2002 hearing, The Status of Research into Vaccine Safety and Autism, held in Washington DC
(8) Ashwood, Murch et al, Royal Free Hospital, London, Intestinal Lymphocyte Populations in Children with Regressive Autism: Evidence for Extensive Mucosal Immunopathology, Journal of Clinical Immunology, Vol 23 No. 6 Nov 2003 pp504-517
(9) Torrente, Anthony et al, Centre for Pediatric Gastroenterology, Royal Free Hospital and University College Medical School, London, Focal-Enhanced Gastritis in Regressive Autism, With Features Distinct from Crohn’s and Helicobacter Pylori Gastritis, American Journal of Gastroenterology, Vol 99, Issue 4, p598, April 2004
(10) Ashwood, Anthony et al, Spontaneous Mucosal Lymphocyte Cytokine Profiles in Children with Autism and Gastrointestinal Symptoms: Mucosal Immune Activation and Reduced Counter-Regulatory Interleukin-10, Journal of Clinical Immunology, Vol 24, No. 6, November 2004
(11) Jyonouchi, Geng et al, Department of Pediatrics, New Jersey Medical School, Dysregulated Innate Immune Responses in Young Children with Autistic Spectrum Disorders - Their Relationship in Gastrointestinal Symptoms and Dietary Intervention, Neuropsychobiology, February 2005, 51 (2) pp77-85
(12) Letter by Balzola, Barbon et al, Department of Gastroenterology, Department of Neuropsychiatry for Children, Department of Pediatric Gastroenterology and Department of Biomedical Sciences and Human Oncology, University of Turin, Pan-Enteric IBD-Like Disease in a Patient with Regressive Autism Shown for the First Time by the Wireless Capsule Enteroscopy - Another Piece in the Jigsaw of this Gut/Brain Syndrome?, American Journal of Gastroenterology, 2005; 100 (4) p979
(13) Balzola, Daniela et al, Department of Gastroenterology, Department of Neuropsychiatry for Children, Department of Pediatric Gastroenterology and Department of Biomedical Science and Human Oncology, University of Turin, Autistic Enterocolitis - Autistic Enterocolitis: Confirmation of a New Inflammatory Bowel Disease in an Italian Cohort of Patients, paper presented to the American Gastroenterological Association, May 2005 and published in Gastroenterology 2005: 128 Suppl 2, A-303
(14) Wakefield, Ashwood et al, The Significance of Ileo-Colonic Lymphoid Nodular Hyperplasia in Children with Autistic Spectrum Disorder, European Journal of Gastroenterology and Hepatology, 2005, Vol 17 No. 8
(15) Gonzalez, Lopez et al, Endoscopic and Histological Characteristics of the Digestive Mucosa in Autistic Children with Gastrointestinal Symptoms: Preliminary Report, G.E.N. Suplemento Especial de Pediatria, no. 1, 2005; pp41-47
Enterocolitis in children with developmental disorders American Journal of Gastroenterology. Volume 95 Page 2285 - September 2000
Autistic disorder and gastrointestinal disease. Curr Opin Pediatr. 2002 Oct;14(5):583-7. Review. PMID: 12352252 [PubMed - indexed for MEDLINE]
Panenteric IBD-Like Disease in a Patient with Regressive Autism Shown for the First Time by the Wireless Capsule Enteroscopy: Another Piece in the Jigsaw of this Gut-Brain Syndrome? The American Journal of Gastroenterology Volume 100 Page 979 - April 2005
Focal-Enhanced Gastritis in Regressive Autism with Features Distinct from Crohn's and Helicobacter Pylori Gastritis American Journal of Gastroenterology
Volume 99 Page 598 - April 2004
Malabsorption and Cerebral Dysfunction: A Multivariate and Comparative Study of Autistic Children
Autism and the gastrointestinal tract American Journal of Gastroenterology Volume 95 Page 2154 - September 2000
The intestinal lesion of autistic spectrum disorder. Eur J Gastroenterol Hepatol. 2005 Aug;17(8):821-2.
Autism - Wakefield AJ, Anthony A, Murch SH, Thomson M, Montgomery SM, Davies S, O'Leary JJ, Berelowitz M, Walker-Smith JA Enterocolitis in children with developmental disorders. Am J Gastroenterol. 2000 Sep;95(9):2285-95
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 Oct;54(Pt 10):987-91.
McGinnis WR.Panenteric IBD-like disease in a patient with regressive autism shown for the first time by the wireless capsule enteroscopy: another piece in the jigsaw of this gut-brain syndrome? Am J Gastroenterol. 2005 Apr;100(4):979-81.
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.
The research is so thorough now, that it conclusively proves a new form of inflammatory bowel disease / enterocolitis as the cause of autism:
The possible association between MMR vaccine, regressive autism and intestinal symptoms was first recounted by parents to Dr. Andrew Wakefield, a UK gastroenterologist at the Royal Free Hospital, London, in 1995. The first group of children presenting in this way to Wakefield and colleagues at the Royal Free were reported in The Lancet as a clinical case series in February 1998 (1). Although the interpretation put on this paper at the time was the subject of intense controversy - particularly in the absence of corroborative clinical research by other researchers at that time - the strong evidence of a hitherto-unreported link between autism and a novel intestinal disease, ileal-lymphoid nodular hyperplasia, has not been disputed, and still stands as an important initial clue as to the causes of regressive autism.
• A group of researchers led by Horvath (2) subsequently independently reported in 1999 upon patients with autism who had gastrointestinal symptoms, including a study of 36 children with autism that found grade I or II reflux esophagitis in 25 (69.4%), chronic gastritis in 15 (42%) and chronic duodenitis in 24 (67%).
Further research published in September 2000 (3) by Wakefield, Anthony et al confirmed that ileal-lymphoid nodular hyperplasia (ILNH) was found in 54 out of 58 (93%) children with autism or other disorders (50 with autism, 5 Aspergers, 2 disintegrative disorder, one ADHD, one schizophrenia, one dyslexia), but only 5 out of 35 (14.3%) normal controls, pointing to a very strong ILNH-autism link.
• Research published in 2001 by Furlano, Anthony et al (4) reported on ileocolonoscopy performed on 21 consecutively-evaluated children with autistic spectrum disorders and bowel symptoms, and made “blinded” comparisons with 8 children who had a histologically normal ileum and colon, plus 10 developmentally-normal children with ILNH, 15 with Crohn’s Disease, and 14 with ulcerative colitis. The study confirmed a distinct lymphocytic colitis in the children with ASD, in which the epithelium appeared particularly affected, offering further corroboration for gut epithelial dysfunction in autism.
• Research reported in 2001 by Buie (5) reported that, as a result of over 400 gastrointestinal endoscopies with biopsies and evaluation of digestive enzyme function, on children with autism, he had found the presence of chronic inflammation of the intestinal tract, although the incidence was less frequent than in the Royal Free Hospital group of patients reported by Wakefield et al, and that biopsy results indicated the presence of chronic inflammation of the digestive tracts, including esophagitis, gastritis and enterocolitis. Ileal lymphoid nodular hyperplasia, as first found by the Royal Free study, had been found in 15 of 89 children examined for it.
• A review (6) published in September 2002 by Wakefield, Anthony, Montgomery et al noted that as early as 1986, a researcher named Soddy had noted that recurrent gastrointestinal upsets were a constant feature of autistic children, and that in a systematic analysis of an unselected population of 385 children on the autistic spectrum, clinically-significant gastrointestinal symptoms occurred in 46%, compared with 10% of 97 developmentally-normal controls, strongly suggesting a gastrointestinal-autism link. Mucosal lesions in the small and large intestine were consistent with an autoimmune pathology, and suggested the possibility of an autoimmune response leading to cerebral damage.
• A June 2002 presentation (7) by Krigsman to the US Congressional Committee on Government Reform reported that a large percentage of his autistic patients suffered from chronic unexplained gastrointestinal symptoms. Of 43 patients, the majority had a clear history of developmental regression, after previous normal development, suffering gradual or precipitous decline between age 12 months and 18 months. Most regressive children also exhibited poor growth. Patients had undergone colonoscopy. Findings were that the lymphoid nodules of the terminal ileum were markedly enlarged, thus confirming the early work of the Royal Free team. Evaluation of biopsy specimens confirmed that 65% had colitis, 51% had active colitis, 40% had chronic colitis, 7% had eosinophilic colitis, 90% had lymphoid nodular hyperplasia of the terminal ileum, and 35% had neither active nor chronic nor eosinophilic colitis. Patterns of inflammation were patchy and unpredictable, but findings were similar and consistent from patient to patient within affected sub-groups.
• A November 2003 paper (8) published by Ashwood, Murch et al reported on the examination of 52 affected autistic children, compared with 25 histologically-normal developmentally-normal controls and a further 54 histologically-inflamed but developmentally-normal controls. Analysis of intestinal biopsies in regressive-autistic children indicated a novel lymphocytic enterocolitis with autoimmune features, though the precise linkage between the finding and cognitive functions still remained unclear. The study concluded that it provided further evidence of a pan-enteric mucosal immunopathology in children with regressive autism, that is distinct from other previously-known inflammatory bowel diseases.
• An April 2004 paper (9) by Torrente, Anthony et al identified, following earlier reports of lymphocytic colitis and small bowel enteropathy in children with regressive autism, that the gastritis in regressive autism was clearly distinct from that in Crohn’s and other conditions, pointing to a distinctive form of gastritis being linked with regressive autism.
• A November 2004 paper (10) by Ashwood, Anthony et al found that molecules (cytokines) produced by immune cells in the intestine, that cause or control inflammation, showed an abnormal pattern in autistic children compared with non-autistic children. The pattern was different to other forms of intestinal inflammation, and the disease resembled a longstanding viral disease of the intestine, not unlike the intestinal inflammation seen on patients with other viral infections such as HIV-associated enteropathy (intestinal disease) that often accompanies infection with HIV.
• A February 2005 paper (11) by Jyonouchi, Geng et al further confirmed the original ileal-lymphoid nodular hyperplasia/regressive autism link first reported by the Wakefield team in 1998. The study again found evidence of marked inflammatory and immune abnormalities in children with autism associated with gastrointestinal symptoms.
• An April 2005 published letter (12) by Balzola, Barbon et al, Pan-Enteric IBD-Like Disease in a Patient with Regressive Autism Shown for the First Time by the Wireless Capsule Enteroscopy - Another Piece in the Jigsaw of this Gut/Brain Syndrome?, reported that a 28-year-old male with regressive autism, severe constipation, bloating, abdomen distension and symptoms of gastroesophageal reflux was examined. Gastroscopy under general anaesthesia revealed hemorrhagic gastritis with inflammatory pseudopolypsthat had reached the pylorum, with a pearl-necklace appearance, and a panenteric IBD-like disease consistent with previously-published descriptions of autistic enterocolitis was finally diagnosed. The wireless capsule images were the first to be obtained beyond the limits of the duodenum and terminal ileum, and demonstrated the potential for the entire bowel to be implicated in this inflammatory disease.
• A May 2005 study (13) by Balzola, Daniela et al reported on 9 consecutive patients (range 7-30 years) with autism and chronic intestinal symptoms (abdominal pain, bloating, constipation and/or diahorrea). Routine blood and stool tests and gastroscopy and colonoscopy with multiple biopsies were performed under sedation, and wireless enteroscopy capsules were used in three of the adult patients. Gastroscopy revealed mucosal gastritis in 4 patients, esophagitis in 1 patient and duodenitis in 1 patient, and histological findings showed chronic inflammation of the stomach and duodenum in 6 patients, inconsistent with celiac disease. The authors reported that preliminary findings were strongly consistent with previous descriptions of autistic enterocolitis, and supported a not-coincidental occurrence. They showed for the first time a small-intestinal involvement, suggesting a pan-enteric localization of this new inflammatory bowel disease.
• Also in 2005, a further paper (14) by Wakefield, Ashwood et al was published, assessing ileocolonic lymphoid nodular hyperplasia in ASD and normal control children. Some 148 consecutive children with ASD, with gastrointestinal symptoms, were investigated by ileocolonoscopy, with 74 ASD children and 23 normal controls undergoing upper gastrointestinal endoscopy. The presence of lymphoid nodular hyperplasia was significantly greater in ASD children compared with controls, in the ileum (129 out of 144, compared with 8 out of 27 controls), and in the colon (88 out of 148, compared with 7 out of 30 controls). Comparative percentages were 90% vs 30% and 59% vs 23%. This was whether or not controls had co-existent colonic inflammation. The severity of ILNH was significantly greater in ASD children compared with controls, with moderate-to-severe ILNH present in 98 out of 144 ASD children compared with 4 out of 27 controls; percentages were 68% and 15%. On histopathological examination, hyperplasic lymphoid follicles were significantly more prevalent in the ileum of ASD children (84 out of 138, or 61%) compared with normal controls (2 out of 23, or 9%). The data thus further corroborated the finding that ileal lymphoid nodular hyperplasia is a significant pathological finding in autistic children.
• Additionally in 2005, a study (15) was published by Gonzalez, Lopez et al, seeking evidence of immunological alterations in 68 autistic children ages 22 months to 11 years and presenting with digestive systems, and examining biopsies from their digestive tracts. Endoscopies and colosopies were undertaken, with biopsies of the esophagus, stomach, duodenum and colon, with verification of presence of inflammation, eosiophil infiltration, lymphoid nodular hyperplasia and CD-4 and CD-8 cells. The results were that lymphoid nodular hyperplasia was discovered in 2/68 esophagus, 6/68 stomachs, 8/68 duodenums and 36/68 (53%) of colons. Eosiophil infiltration with more than 20 eosiphils per field were found in 3/68 eosphagus, 1/68 stomach, 8/68 duodenum and 24/68 (35%) colons. Inflammatory reactions were found in 56/68 (82%) esophogitis, 64/68 (94%) gastritis, and all (100%) presented with duodenitis and colitis. CD-4/CD-8 relationship existed of >3 in 42/68 (62%) and <1 in 16/68. The authors concluded that the children presented immunological and immunohistochemical alterations of the biopsies of their digestive tracts, and that there was a significant finding of lymphoid nodular hyperplasia, eosiophilinfiltration, and that prevalence of greater CD-4 than CD-8 cells in the inflammation of the intestinal wall demonstrated in favour of a Th2 type allergic reaction.
* 1) Wakefield et al, Inflammatory Bowel Disease Study Group, Royal Free Hospital London, Ileal Lymphoid Nodular Hyperplasia, Non Specific Colitis and Pervasive Development Disorder in Children, Lancet, 28th February 1998
(2) Horvath, Papadimitiou et al, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Gastrointestinal Abnormalities in Children With Autistic Disorder, Journal of Pediatrics, 1999 November, Vol 135 (5), pp559-563
(3) Wakefield, Anthony et al, Enterocolitis in Children with Developmental Disorders, American Journal of Gastroenterology, Sept 2000, Vol 95, No. 9, pp2285-2295
(4) Furlano, Anthony et al, Colonic CD8 and T-Cell Infiltration With Epithelial Damage in Children with Autism, Journal of Pediatrics, 2001; 138; No. 3, 366-372
(5) Paper by Dr. Timothy Buie, Harvard Massachusetts General Hospital, presented to the Oasis 2001 Conference for Autism, Portland, Oregon, November 2001
(6) Wakefield, Anthony, Montgomery et al, Inflammatory Bowel disease Study Group, Royal Free Hospital, University College Medical School, London, and Coombe Women’s Hospital and Trinity College Dublin, The Concept of Enterocolonic Encepalopathy, Autism and Opioid Receptor Ligands, Aliment Pharmacological Ther, 16: pp663-674
(7) Presentation by Krigsman to the US Congressional Committee on Government Reform’s June 2002 hearing, The Status of Research into Vaccine Safety and Autism, held in Washington DC
(8) Ashwood, Murch et al, Royal Free Hospital, London, Intestinal Lymphocyte Populations in Children with Regressive Autism: Evidence for Extensive Mucosal Immunopathology, Journal of Clinical Immunology, Vol 23 No. 6 Nov 2003 pp504-517
(9) Torrente, Anthony et al, Centre for Pediatric Gastroenterology, Royal Free Hospital and University College Medical School, London, Focal-Enhanced Gastritis in Regressive Autism, With Features Distinct from Crohn’s and Helicobacter Pylori Gastritis, American Journal of Gastroenterology, Vol 99, Issue 4, p598, April 2004
(10) Ashwood, Anthony et al, Spontaneous Mucosal Lymphocyte Cytokine Profiles in Children with Autism and Gastrointestinal Symptoms: Mucosal Immune Activation and Reduced Counter-Regulatory Interleukin-10, Journal of Clinical Immunology, Vol 24, No. 6, November 2004
(11) Jyonouchi, Geng et al, Department of Pediatrics, New Jersey Medical School, Dysregulated Innate Immune Responses in Young Children with Autistic Spectrum Disorders - Their Relationship in Gastrointestinal Symptoms and Dietary Intervention, Neuropsychobiology, February 2005, 51 (2) pp77-85
(12) Letter by Balzola, Barbon et al, Department of Gastroenterology, Department of Neuropsychiatry for Children, Department of Pediatric Gastroenterology and Department of Biomedical Sciences and Human Oncology, University of Turin, Pan-Enteric IBD-Like Disease in a Patient with Regressive Autism Shown for the First Time by the Wireless Capsule Enteroscopy - Another Piece in the Jigsaw of this Gut/Brain Syndrome?, American Journal of Gastroenterology, 2005; 100 (4) p979
(13) Balzola, Daniela et al, Department of Gastroenterology, Department of Neuropsychiatry for Children, Department of Pediatric Gastroenterology and Department of Biomedical Science and Human Oncology, University of Turin, Autistic Enterocolitis - Autistic Enterocolitis: Confirmation of a New Inflammatory Bowel Disease in an Italian Cohort of Patients, paper presented to the American Gastroenterological Association, May 2005 and published in Gastroenterology 2005: 128 Suppl 2, A-303
(14) Wakefield, Ashwood et al, The Significance of Ileo-Colonic Lymphoid Nodular Hyperplasia in Children with Autistic Spectrum Disorder, European Journal of Gastroenterology and Hepatology, 2005, Vol 17 No. 8
(15) Gonzalez, Lopez et al, Endoscopic and Histological Characteristics of the Digestive Mucosa in Autistic Children with Gastrointestinal Symptoms: Preliminary Report, G.E.N. Suplemento Especial de Pediatria, no. 1, 2005; pp41-47
Enterocolitis in children with developmental disorders American Journal of Gastroenterology. Volume 95 Page 2285 - September 2000
Autistic disorder and gastrointestinal disease. Curr Opin Pediatr. 2002 Oct;14(5):583-7. Review. PMID: 12352252 [PubMed - indexed for MEDLINE]
Panenteric IBD-Like Disease in a Patient with Regressive Autism Shown for the First Time by the Wireless Capsule Enteroscopy: Another Piece in the Jigsaw of this Gut-Brain Syndrome? The American Journal of Gastroenterology Volume 100 Page 979 - April 2005
Focal-Enhanced Gastritis in Regressive Autism with Features Distinct from Crohn's and Helicobacter Pylori Gastritis American Journal of Gastroenterology
Volume 99 Page 598 - April 2004
Malabsorption and Cerebral Dysfunction: A Multivariate and Comparative Study of Autistic Children
Autism and the gastrointestinal tract American Journal of Gastroenterology Volume 95 Page 2154 - September 2000
The intestinal lesion of autistic spectrum disorder. Eur J Gastroenterol Hepatol. 2005 Aug;17(8):821-2.
Autism - Wakefield AJ, Anthony A, Murch SH, Thomson M, Montgomery SM, Davies S, O'Leary JJ, Berelowitz M, Walker-Smith JA Enterocolitis in children with developmental disorders. Am J Gastroenterol. 2000 Sep;95(9):2285-95
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 Oct;54(Pt 10):987-91.
McGinnis WR.Panenteric IBD-like disease in a patient with regressive autism shown for the first time by the wireless capsule enteroscopy: another piece in the jigsaw of this gut-brain syndrome? Am J Gastroenterol. 2005 Apr;100(4):979-81.
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.
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