Skip to main content

Advertisement

Log in

Gastrointestinal Factors in Autistic Disorder: A Critical Review

  • Published:
Journal of Autism and Developmental Disorders Aims and scope Submit manuscript

Abstract

Interest in the gastrointestinal (GI) factors of autistic disorder (autism) has developed from descriptions of symptoms such as constipation and diarrhea in autistic children and advanced towards more detailed studies of GI histopathology and treatment modalities. This review attempts to critically and comprehensively analyze the literature as it applies to all aspects of GI factors in autism, including discussion of symptoms, pathology, nutrition, and treatment. While much literature is available on this topic, a dearth of rigorous study was found to validate GI factors specific to children with autism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Afzal N., Murch S., Thirrupathy K., Berger L., Fagbemi A., Heuschkel R. (2003). Constipation with acquired megarectum in children with autism Pediatrics 112: 939–942

    Article  PubMed  Google Scholar 

  • Ahearn W. H., Castine T., Nault K., Green G. (2001). An assessment of food acceptance in children with autism or pervasive developmental disorder-not otherwise specified Journal of Autism and Developmental Disorders 31: 505–511

    Article  PubMed  Google Scholar 

  • Alberti A., Pirrone P., Elia M., Waring R. H., Romano C. (1999). Sulphation deficit in “low-functioning” autistic children: A pilot study Biological Psychiatry 46: 420–424

    Article  PubMed  Google Scholar 

  • American Psychiatric Association, (1987). Diagnostic and statistical manual of mental disorders (3rd ed., revised). American Psychiatric Association

  • Banov C. H. (1979). Risks with controlling diet Journal of Autism and Developmental Disorders 9: 135–136

    Article  PubMed  Google Scholar 

  • Black C., Kaye J. A., Jick H. (2002). Relation of childhood gastrointestinal disorders to autism: Nested case–control study using data from the UK General Practice Research Database British Medical Journal 325: 419–421

    Article  PubMed  Google Scholar 

  • Carey T., Ratliff-Schaub K., Funk J., Weinle C., Myers M., Jenks J. (2002). Double-blind placebo-controlled trial of secretin: Effects on aberrant behavior in children with autism Journal of Autism and Developmental Disorders 32: 161–167

    Article  PubMed  Google Scholar 

  • Chez M. G., Buchanan C. P., Bagan B. T. (2000). Secretin and autism: A two part clinical investigation Journal of Autism and Developmental Disorders 30: 87–94

    Article  PubMed  Google Scholar 

  • Cohen D. J., Johnson W. T., Caparulo B. K. (1976). Pica and elevated blood lead level in autistic and atypical children American Journal of Diseases of Children 130: 47–48

    PubMed  Google Scholar 

  • Coniglio S. J., Lewis J. D., Lang C., Burns T. G. (2001). A randomized, double-blind, placebo controlled trial of single-dose intravenous secretin as a treatment for children with autism Journal of Pediatrics 138: 649–655

    Article  PubMed  Google Scholar 

  • Corbett, B., Khan, K., Czapansky-Beilman, D., & Brady, N. (2001). A double-blind, placebo-controlled crossover study investigating the effect of porcine secretin in children with autism. Clinical Pediatrics, 325–331

  • Cornish E. (2002). Gluten and casein free diets in autism: A study of the effects on food choice and nutrition Journal of Human Nutrition and Dietetics 15: 261–269

    Article  PubMed  Google Scholar 

  • D’Eufemia P., Celli M., Finocchiaro R., Pacifico L., Viozzi L., Zaccagnini M., Cardi E., Giardini O. (1996). Abnormal intestinal permeability in children with autism Acta Paediatrica 85: 1076–1079

    Article  PubMed  Google Scholar 

  • Dalrymple N. J., Ruble L. A. (1992). Toilet training and behaviors of people with autism: Parent views Journal of Autism and Developmental Disorders 22: 265–275

    Article  PubMed  Google Scholar 

  • Dunn-Geier J., Ho H. H., Auersperg E., Coyle D. (2000). Effect of secretin on children with autism: A randomized controlled trial Developmental Medicine & Child Neurology 42: 796–802

    Article  Google Scholar 

  • Evangeliou A., Vlachonikolis I., Mihailidou H. (2003). Application of ketogenic diet in children with autistic behavior: Pilot study Journal of Child Neurology 18: 113–118

    Article  PubMed  Google Scholar 

  • Field D., Garland M., Williams K. (2003). Correlates of specific childhood feeding problems Journal of Pediatric Child Health 39: 299–304

    Article  Google Scholar 

  • Finegold S. M., Molitoris D., Song Y., Liu C., Vaisanen M. L., Bolte E., McTeague M., Sandler R., Wexler H. (2002). Gastrointestinal microflora studies in late-onset autism Clinical Infectious Diseases 35: S6–S16

    Article  PubMed  Google Scholar 

  • Fombonne E., Chakrabarti S. (2001). No evidence for a new variant of measles-mumps-rubella-induced autism Pediatrics 108(4): E58

    Article  PubMed  Google Scholar 

  • Furlano R. L., Anthony A., Day R., Brown A., McGarvey L., Thomson M. A., Davies S. E., Berelowitz M., Frobes A., Wakefield A. J., Walker-Smith J. A., Murch S. H. (2001). Colonic CD8 and gamma delta T-cell infiltration with epithelial damage in children with autism Journal of Pediatrics 138: 366–372

    Article  PubMed  Google Scholar 

  • Hendrickson B. A., Turner J. R. (2002). MMR vaccination, ileal lymphoid nodular hyperplasia, and pervasive developmental disorder Lancet 359: 2051–2052

    Article  PubMed  Google Scholar 

  • Hoekstra J. H. (1998). Toddler diarrhoea: A more nutritional disorder than a disease Archives of Disease in Childhood 79: 2–5

    Article  PubMed  Google Scholar 

  • Honomichl R. D., Goodlin-Jones B. L., Burnham M. M., Hansen R. L., Anders T. F. (2002). Secretin and sleep in children with autism Child Psychiatry and Human Development 33: 107–123

    Article  PubMed  Google Scholar 

  • Horvath K., Medeiros L., Rabszlyn A. (2000a). High prevalence of gastrointestinal symptoms in autistic children with autistic spectrum disorder Journal of Pediatric Gastroenterology and Nutrition 31: S174

    Google Scholar 

  • Horvath K., Papadimitriou J. C., Rabsztyn A., Drachenberg C., Tildon J. T. (1999). Gastrointestinal abnormalities in children with autistic disorder Journal of Pediatrics 135: 559–563

    Article  PubMed  Google Scholar 

  • Horvath K., Perman J. A. (2002a). Autism and gastrointestinal symptoms Current Gastroenterology Reports 4: 251–258

    Article  Google Scholar 

  • Horvath K., Perman J. A. (2002b). Autistic disorder and gastrointestinal disease Current Opinion in Pediatrics 14: 583–587

    Article  Google Scholar 

  • Horvath K., Stefanatos G., Sokolski K. N., Wachtel R., Nabors L., Tildon J. T. (1998). Improved social and language skills after secretin administration in patients with autistic spectrum disorders Journal of the American Association for Academic Minority Physicians 9: 9–15

    Google Scholar 

  • Horvath K., Zielke R. H., Collins R. M., Rabsztyn A., Medeiros L. A., Perman J. (2000b). Secretin improves intestinal permeability in autistic children Journal of Pediatric Gastroenterology and Nutrition 31: S31

    Google Scholar 

  • Jyonouchi H., Sun S., Itokazu N. (2002). Innate immunity associated with inflammatory responses and cytokine production against common dietary proteins in patients with autism spectrum disorder Neuropsychobiology 46: 76–84

    Article  PubMed  Google Scholar 

  • Kaminska B., Czaja M., Kozielska E., Mazur E., Korzon M. (2002). Use of secretin in treatment of childhood autism Medical Science Monitor 8: RA22–26

    PubMed  Google Scholar 

  • Kawashima H., Mori T., Kashiwagi Y., Takekuma K., Hoshika A., Wakefield A. J. (2000). Detection and sequencing of measles virus from peripheral mononuclear cells from patients with inflammatory bowel disease and autism Digestive Diseases and Sciences 45: 723–729

    Article  PubMed  Google Scholar 

  • Kern J. K., Miller V. S., Evans P. A., Trivedi M. H. (2002). Efficacy of porcine secretin in children with autism and pervasive developmental disroder Journal of Autism and Developmental Disorders 32: 153–160

    Article  PubMed  Google Scholar 

  • Knivsberg A., Reichelt K. L., Nodland N., Hoien T. (1995). Autistic syndrome and diet: A follow-up study Scandinavian Journal of Education and Research 39: 223–236

    Article  Google Scholar 

  • Knivsberg A. M., Reichelt K. L., Hoien T., Nodland M. (2002). A randomized, controlled study of dietary intervention in autistic syndromes Nutritional Neuroscience 5: 251–261

    Article  PubMed  Google Scholar 

  • Kokkonen J., Karttunen T. J. (2002). Lymphonodular hyperplasia on the mucosa of the lower gastrointestinal tract in children: An indication of enhanced immune response? Journal of Pediatric Gastroenterology and Nutrition 34: 42–46

    Article  PubMed  Google Scholar 

  • Kuddo T., Nelson K. B. (2003). How common are gastrointestinal disorders in children with autism? Current Opinion in Pediatrics 15: 339–343

    Article  PubMed  Google Scholar 

  • Lightdale J. R., Hayer C., Duer A., Lind-White C., Jenkins S., Siegel B., Elliot G. R., Heyman M. B. (2001). Effects of intravenous secretin on language and behavior of children with autism and gastrointestinal symptoms: A single-blinded, open-label pilot study Pediatrics 108: E90

    Article  PubMed  Google Scholar 

  • Lightdale J. R., Siegel B., Heyman M. B. (2001). Gastrointestinal symptoms in autistic children Clinical Perspectives on Gastroenterology 1: 56–58

    Google Scholar 

  • Linday L. A. (1997). Oral famotidine: A potential treatment for children with autism Medical Hypotheses 48: 381–386

    Article  PubMed  Google Scholar 

  • Linday L. A., Tsiouris J. A., Cohen I. L., Shindledecker R., DeCresce R. (2001). Famotidine treatment of children with autistic spectrum disorders: Pilot research using single subject research design Journal of Neural Transmission 108: 593–611

    Article  PubMed  Google Scholar 

  • Loening-Baucke V. (1998). Constipation in children The New England Journal of Medicine 339: 1155–1156

    Article  PubMed  Google Scholar 

  • Lucarelli S., Frediani T., Zingoni A. M., Ferruzzi F., Giardini O., Quintieri F., Barbato M., D’Eufemia P., Cardi E. (1995). Food allergy and infantile autism Panminerva Medica 37: 137–141

    PubMed  Google Scholar 

  • Malloy C. A., Manning-Courtney P., Swayne S., Bean J., Brown J. M., Murray D. S., Kinsman A. M., Brasington M., Ulrich C. D. (2002). Lack of benefit of intravenous synthetic human secretin in the treatment of autism Journal of Autism and Developmental Disorders 32: 545–551

    Article  Google Scholar 

  • McCarthy D. M., Coleman M. (1979). Response of intestinal mucosa to gluten challenge in autistic subjects Lancet 2: 877–878

    Article  PubMed  Google Scholar 

  • McMillin D. L., Richards D. G., Mein E. A., Nelson C. D. (1999). The abdominal brain and the enteric nervous system Journal of Alternative and Complementary Medicine 5: 575–586

    Article  Google Scholar 

  • Melmed R. D., Schneider C. K., Fabes R. A., Phillips J., Reichelt K. (2000). Metabolic markers and gastrointestinal symptoms in children with autism and related disorders Journal of Pediatric Gastroenterology and Nutrition 3: S31–S32

    Google Scholar 

  • Murch S. H., MacDonald T. T., Walker-Smith J. A., Levin M., Lionetti P., Klein N. J. (1993). Disruption of sulphated glycosaminoglycans in intestinal inflammation Lancet 341: 711–714

    Article  PubMed  Google Scholar 

  • O’Banion D., Armstrong B., Cummings R. A., Strange J. (1978). Disruptive behavior: A dietary approach Journal of Autism and Childhood Schizophrenia 8: 325–337

    Article  PubMed  Google Scholar 

  • Owley T., McMahon W., Cook E. H., Laulhere T., South M., Zellmer L. (2001). Multisite, double blind, placebo-controlled trial of porcine secretin in autism Journal of the American Academy of Child and Adolescent Psychiatry 40: 1293–1299

    Article  PubMed  Google Scholar 

  • Patel N. C., Yeh J. Y., Shepherd M. D., Crismon M. L. (2002). Secretin treatment for autistic disorder: A critical analysis Pharmacotherapy 22: 905–914

    Article  PubMed  Google Scholar 

  • Pavone L., Fiumara A., Bottaro G., Mazzone D., Coleman M. (1997). Autism and celiac disease: Failure to validate the hypothesis that a link might exist Biological Psychiatry 42: 72–75

    Article  PubMed  Google Scholar 

  • Quigley E. M. (2000). Autism and the gastrointestinal tract American Journal of Gastroenterology 95: 2154–2156

    Article  PubMed  Google Scholar 

  • Raiten D. J., Massaro T. (1986). Perspectives on the nutritional ecology of autistic children Journal of Autism and Developmental Disorders 16: 133–143

    Article  PubMed  Google Scholar 

  • Reichelt K. L., Ekrein J., Scott H. (1990). Gluten, milk proteins and autism: Dietary intervention effects on behavior and peptide secretion Journal of Applied Nutrition 42: 1–11

    Google Scholar 

  • Reichelt K. L., Knivsberg A. M., Lind G., Nodland M. (1991). Probable etiology and possible treatment of childhood autism Brain Dysfunction 4: 308–319

    Google Scholar 

  • Roberts W., Weaver L., Brian J., Bryson S. (2001). Repeated doses of porcine secretin in the treatment of autism: A randomized, placebo controlled trial Pediatrics 107: e71

    Article  PubMed  Google Scholar 

  • Sandler A. D., Sutton K. A., DeWeese J., Girardi M. A., Sheppard V., Bodfish J. W. (1999). Lack of benefit of a single dose of synthetic human secretin in the treatment of autism and pervasive developmental disorder The New England Journal of Medicine 341: 1801–1806

    Article  PubMed  Google Scholar 

  • Sandler R. H., Finegold S. M., Bolte E. R., Buchanan C., Maxwell A. P., Vaisanen M. L., Nelson M. N., Wexler H. (2000). Short-term benefit from oral vancomycin treatment of regressive-onset autism Journal of Child Neurology 15: 429–435

    Article  PubMed  Google Scholar 

  • Shearer T. R., Larson K., Neushwander J., Gedney B. (1982). Minerals in the hair and nutrient intake of autistic children Journal of Autism and Developmental Disorders 12: 25–34

    Article  PubMed  Google Scholar 

  • Sponheim E., Oftedal G., Helverschou B. (2002). Multiple doses of secretin in the treatment of autism: A controlled study Acta Paediatrica 91: 540–545

    Article  PubMed  Google Scholar 

  • Tanguay P. E. (2002). Commentary: The primacy of the scientific method Journal of the American Academy of Child and Adolescent Psychiatry 41: 1322–1323

    Article  PubMed  Google Scholar 

  • Taylor B., Miller E., Lingam R. (2002). Measles, mumps, and rubella vaccination and bowel problems or developmental regression in children with autism: Population study British Medical Journal 324: 393–396

    Article  PubMed  Google Scholar 

  • Torrente F., Ashwood P., Day R., Machado N., Furlano R. I., Anthony A., Davies S. E., Wakefield A. J., Thomson M. A., Walker-Smith J. A., Murch S. H. (2002). Small intestinal enteropathy with epithelial IgG and complement deposition in children with regressive autism Molecular Psychiatry 7: 375–382

    Article  PubMed  Google Scholar 

  • Uhlmann V., Martin C. M., Scheils O., Pilkington L., Silva I., Killalea A., Murch S. B., Walker-Smith J. A., Thomson M. A., Wakefield A. J., O’Leary J. J. (2002). Potential viral pathogenic mechanism for a new variant inflammatory bowel disease Journal of Clinical Pathology – Molecular Pathology 55: 84–90

    Google Scholar 

  • Unis I. S., Munson J. A., Rogers S. J., Goldson E., Osterling J., Gabriels R., Abbott R. D., Dawson G. (2002). A randomized, double-blind, placebo controlled trial of porcine versus synthetic secretin for reducing symptoms of autism Journal of the American Academy of Child and Adolescent Psychiatry 41: 1315–1321

    Article  PubMed  Google Scholar 

  • Wakefield A. J., Anthony A., Murch S. H., Thomson M. A., Montgomery S. M., Davies S., O’Leary J. J., Berelowitz M., Walker-Smith J. A. (2003). Enterocolitis in children with developmental disabilities The American Journal of Gastroenterology 95: 2285–2295

    Article  Google Scholar 

  • Wakefield A. J., Anthony A., Schepelmann S., Kawashima H., Sim R., Khan K., Murch S. H., Dhillon A. P., Montgomery S. M., Thomson M. A., Thomas J., Walker-Smith J. A. (1998a). Persistent measles virus (MV) infection and immunodeficiency in children with autism, ileo-colonic lymphonodular hyperplasia and non-specific colitis Gut 42: A86

    Google Scholar 

  • Wakefield A. J., Murch S. H., Anthony A., Linnell J., Casson D. M., Malik M., Berelowitz M., Dhillon A. P., Thomson M. A., Harvey P., Valentine A., Davies S. E. (1998b). Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children Lancet 351: 637–641

    Article  Google Scholar 

  • Wakefield A. J., Murch S. H., Anthony A., Linnell J., Thomas J., Berelowitz M., Dhillon A. P., Thomson M. A., Davies S. E., Walker-Smith J. A. (1998c). Autistic enteropathy: A new inflammatory bowel disease? Gut 42: A84–A85

    Google Scholar 

  • Wakefield A. J., Puleston J. M., Montgomery S. M., Anthony A., O’Leary J. J., Murch S. H. (2002). Review article: The concept of entero-colonic encephalopathy, autism and opioid receptor ligands Alimentary Pharmacology and Therapeutics 16: 663–674

    Article  PubMed  Google Scholar 

  • Walker-Smith J. A., Andrews J. (1972). Alpha-antitrypsin, autism and celiac disease Lancet 2: 883–884

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported in part by a Daniel X. Freedman Psychiatric Research Fellowship Award (Dr. Posey), a National Alliance for Research in Schizophrenia and Depression (NARSAD) Young Investigator Award (Dr. Posey), a Research Unit on Pediatric Psychopharmacology Grant (U10-MH66766-02) from the National Institute of Mental Health (NIMH) to Indiana University (Drs. McDougle, Stigler, and Posey), a Research Career Development Award (K23-MH068627-01) from NIMH (Dr. Posey), a National Institutes of Health Clinical Research Center Grant to Indiana University (M01-RR00750), and a Department of Housing and Urban Development (HUD) Grant No. B-01-SP-IN-0200 (Dr. McDougle).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christopher J. McDougle.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Erickson, C.A., Stigler, K.A., Corkins, M.R. et al. Gastrointestinal Factors in Autistic Disorder: A Critical Review. J Autism Dev Disord 35, 713–727 (2005). https://doi.org/10.1007/s10803-005-0019-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10803-005-0019-4

Keywords

Navigation