Abnormal intestinal permeability in children with autism
Abstract
We determined the occurrence of gut mucosal damage using the intestinal permeability test in 21 autistic children who had no clinical and laboratory findings consistent with known intestinal disorders. An altered intestinal permeability was found in 9 of the 21 (43%) autistic patients, but in none of the 40 controls. Compared to the controls, these nine patients showed a similar mean mannitol recovery, but a significantly higher mean lactulose recovery (1.64% +/- 1.43 vs 0.38% +/- 0.14; P < 0.001). We speculate that an altered intestinal permeability could represent a possible mechanism for the increased passage through the gut mucosa of peptides derived from foods with subsequent behavioural abnormalities.
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ASD subjects display substantial alterations in microbiota composition.
“There is a growing body of evidence that ASD subjects display substantial alterations in microbiota composition, along with marked symptoms of GI distress, including changes to bowel habits, increased intestinal permeability, bloating and abdominal pain (Angelis et al., 2013; D'Eufemia et al., 1996; Kang et al., 2013; Luna et al., 2017; McElhanon et al., 2014; Tomova et al., 2015).”
From Microbiota-related Changes in Bile Acid & Tryptophan Metabolism are Associated with Gastrointestinal Dysfunction in a Mouse Model of Autism (2017) · cites this paper as D'Eufemia et al., 1996
Many children with ASD show abnormalities in GI physiology, including increased intestinal permeability, overall microbiota alterations, and gut infection with cresol-producing Clostridium difficile.
“Many ASD children have also been shown to carry abnormalities in GI physiology, including: increased intestinal permeability [34,35], overall microbiota alterations [36,37,38,39,40], and gut infection with cresol-producing Clostridium difficile [39,41,42,43,44].”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [34]
In ASD, abnormal intestinal permeability could allow 5-HT to translocate into the systemic circulation, leading to elevated levels of blood 5-HT.
“In ASD, abnormal intestinal permeability could allow 5′-HT to translocate into the systemic circulation, leading to elevated levels of blood 5′-HT [34,35,127,193].”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [34]
Children with ASD and gastrointestinal symptoms present with immune imbalances in the gut that could be associated with abnormal host responses to microbial dysbiosis and impaired gut barrier integrity.
“Furthermore, children with ASD and gastrointestinal symptoms also present with immune imbalances in the gut that could be associated with abnormal host responses to microbial dysbiosis and impaired gut barrier integrity [16–19].”
From Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms (2019) · cites this paper as [16]
Cites
Aspects of Autism: Biological Research
Merjanian, P. M. (1989) · Trends in Neurosciences · doi:10.1016/0166-2236(89)90086-6 · Cited by 110 · see citing works
Childhood psychosis and urinary excretion of peptides and protein-associated peptide complexes
Gilberg, C., Trygstad, O., & Foss, I. (1982) · Journal of Autism and Developmental Disorders · doi:10.1007/bf01531369 · Cited by 33 · see citing works
Autism: current understanding and management.
Le Couteur, A. (1990) · PubMed · Cited by 6 · see citing works
Choosing a management course for doctors.
Hindle, J. (1990) · PubMed · Cited by 5 · see citing works
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Sorted by citations
Hsiao, E. Y., McBride, S. W., Hsien, S., Sharon, G., Hyde, E. R., McCue, T., Codelli, J. A., Chow, J., Reisman, S. E., Petrosino, J. F., et al. (2013) · Cell · doi:10.1016/j.cell.2013.11.024 · Cited by 3,283 · see citing works
Wakefield, A., Murch, S., Anthony, A., Linnell, J., Casson, D., Malik, M., Berelowitz, M., Dhillon, A., Thomson, M., Harvey, P., et al. (1998) · The Lancet · doi:10.1016/s0140-6736(97)11096-0 · Cited by 3,006 · see citing works
RetractedBuie, T., Campbell, D. B., Fuchs, G. J., Furuta, G. T., Levy, J., VandeWater, J., Whitaker, A. H., Atkins, D., Bauman, M. L., Beaudet, A. L., et al. (2010) · Pediatrics · doi:10.1542/peds.2009-1878c · Cited by 872 · see citing works
Gastrointestinal Microflora Studies in Late‐Onset Autism
Finegold, S. M., Molitoris, D., Song, Y., Liu, C., Vaisanen, M., Bolte, E., McTeague, M., Sandler, R., Wexler, H., Marlowe, E. M., et al. (2002) · Clinical Infectious Diseases · doi:10.1086/341914 · Cited by 742 · see citing works
Gastrointestinal microbiota in children with autism in Slovakia
Tomova, A., Husarova, V., Lakatosova, S., Bakos, J., Vlkova, B., Babinska, K., & Ostatnikova, D. (2015) · Physiology & Behavior · doi:10.1016/j.physbeh.2014.10.033 · Cited by 632 · see citing works
The bowel and beyond: The enteric nervous system in neurological disorders
Rao, M., & Gershon, M. D. (2016) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.107 · Cited by 629 · see citing works
Emerging Roles for the Gut Microbiome in Autism Spectrum Disorder
Vuong, H. E., & Hsiao, E. Y. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.08.024 · Cited by 595 · see citing works
de Magistris, L., Familiari, V., Pascotto, A., Sapone, A., Frolli, A., Iardino, P., Carteni, M., De Rosa, M., Francavilla, R., Riegler, G., et al. (2010) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0b013e3181dcc4a5 · Cited by 546 · see citing works
The immune response in autism: a new frontier for autism research
Ashwood, P., Wills, S., & Van de Water, J. (2006) · Journal of Leukocyte Biology · doi:10.1189/jlb.1205707 · Cited by 528 · see citing works
Sturgeon, C., & Fasano, A. (2016) · Tissue Barriers · doi:10.1080/21688370.2016.1251384 · Cited by 497 · see citing works
Blood–brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders
Fiorentino, M., Sapone, A., Senger, S., Camhi, S. S., Kadzielski, S. M., Buie, T. M., Kelly, D. L., Cascella, N., & Fasano, A. (2016) · Molecular Autism · doi:10.1186/s13229-016-0110-z · Cited by 494 · see citing works
Williams, B. L., Hornig, M., Buie, T., Bauman, M. L., Cho Paik, M., Wick, I., Bennett, A., Jabado, O., Hirschberg, D. L., & Lipkin, W. I. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024585 · Cited by 492 · see citing works
Wang, L., Christophersen, C. T., Sorich, M. J., Gerber, J. P., Angley, M. T., & Conlon, M. A. (2011) · Applied and Environmental Microbiology · doi:10.1128/aem.05212-11 · Cited by 432 · see citing works
Wang, L., Christophersen, C. T., Sorich, M. J., Gerber, J. P., Angley, M. T., & Conlon, M. A. (2013) · Molecular Autism · doi:10.1186/2040-2392-4-42 · Cited by 418 · see citing works
Fecal Microbiota Transplantation in Neurological Disorders
Vendrik, K. E. W., Ooijevaar, R. E., de Jong, P. R. C., Laman, J. D., van Oosten, B. W., van Hilten, J. J., Ducarmon, Q. R., Keller, J. J., Kuijper, E. J., & Contarino, M. F. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.00098 · Cited by 413 · see citing works
Wang, L., Christophersen, C. T., Sorich, M. J., Gerber, J. P., Angley, M. T., & Conlon, M. A. (2012) · Digestive Diseases and Sciences · doi:10.1007/s10620-012-2167-7 · Cited by 412 · see citing works
Williams, B. L., Hornig, M., Parekh, T., & Lipkin, W. I. (2012) · mBio · doi:10.1128/mbio.00261-11 · Cited by 378 · see citing works
Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders
Kang, D.-W., Ilhan, Z. E., Isern, N. G., Hoyt, D. W., Howsmon, D. P., Shaffer, M., Lozupone, C. A., Hahn, J., Adams, J. B., & Krajmalnik-Brown, R. (2018) · Anaerobe · doi:10.1016/j.anaerobe.2017.12.007 · Cited by 381 · see citing works
Golubeva, A. V., Joyce, S. A., Moloney, G., Burokas, A., Sherwin, E., Arboleya, S., Flynn, I., Khochanskiy, D., Moya-Pérez, A., Peterson, V., et al. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.09.020 · Cited by 364 · see citing works
Incidence of Gastrointestinal Symptoms in Children With Autism: A Population-Based Study
Ibrahim, S. H., Voigt, R. G., Katusic, S. K., Weaver, A. L., & Barbaresi, W. J. (2009) · PEDIATRICS · doi:10.1542/peds.2008-2933 · Cited by 298 · see citing works
Holingue, C., Newill, C., Lee, L., Pasricha, P. J., & Daniele Fallin, M. (2018) · Autism Research · doi:10.1002/aur.1854 · Cited by 296 · see citing works
Gastrointestinal Conditions in Children With Autism Spectrum Disorder: Developing a Research Agenda
Coury, D. L., Ashwood, P., Fasano, A., Fuchs, G., Geraghty, M., Kaul, A., Mawe, G., Patterson, P., & Jones, N. E. (2012) · Pediatrics · doi:10.1542/peds.2012-0900n · Cited by 264 · see citing works
Evidence of Toxicity, Oxidative Stress, and Neuronal Insult in Autism
Kern, J. K., & Jones, A. M. (2006) · Journal of Toxicology and Environmental Health, Part B · doi:10.1080/10937400600882079 · Cited by 265 · see citing works
Autism and gastrointestinal symptoms
Horvath, K., & Perman, J. A. (2002) · Current Gastroenterology Reports · doi:10.1007/s11894-002-0071-6 · Cited by 260 · see citing works
Sanctuary, M. R., Kain, J. N., Chen, S. Y., Kalanetra, K., Lemay, D. G., Rose, D. R., Yang, H. T., Tancredi, D. J., German, J. B., Slupsky, C. M., et al. (2019) · PLOS ONE · doi:10.1371/journal.pone.0210064 · Cited by 255 · see citing works
Molloy, C. A., & Manning-Courtney, P. (2003) · Autism · doi:10.1177/1362361303007002004 · Cited by 249 · see citing works
Gastrointestinal symptoms in a sample of children with pervasive developmental disorders
Nikolov, R. N., Bearss, K. E., Lettinga, J., Erickson, C., Rodowski, M., Aman, M. G., McCracken, J. T., McDougle, C. J., Tierney, E., Vitiello, B., et al. (2009) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-008-0637-8 · Cited by 240 · see citing works
Rose, D. R., Yang, H., Serena, G., Sturgeon, C., Ma, B., Careaga, M., Hughes, H. K., Angkustsiri, K., Rose, M., Hertz-Picciotto, I., et al. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.03.025 · Cited by 227 · see citing works
Jyonouchi, H., Sun, S., & Itokazu, N. (2002) · Neuropsychobiology · doi:10.1159/000065416 · Cited by 225 · see citing works
Autistic disorder and gastrointestinal disease
Horvath, K., & Perman, J. A. (2002) · Current Opinion in Pediatrics · doi:10.1097/00008480-200210000-00004 · Cited by 224 · see citing works
The “psychomicrobiotic”: targeting microbiota in major psychiatric disorders: a systematic review
Fond, G., Boukouaci, W., Chevalier, G., Regnault, A., Eberl, G., Hamdani, N., Dickerson, F., Macgregor, A., Boyer, L., Dargel, A., et al. (2015) · Pathologie Biologie · doi:10.1016/j.patbio.2014.10.003 · Cited by 219 · see citing works
Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions
Ristori, M. V., Quagliariello, A., Reddel, S., Ianiro, G., Vicari, S., Gasbarrini, A., & Putignani, L. (2019) · Nutrients · doi:10.3390/nu11112812 · Cited by 214 · see citing works
Gastrointestinal issues in autism spectrum disorder
Hsiao, E. Y. (2014) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000029 · Cited by 209 · see citing works
Ashwood, P., & Wakefield, A. J. (2006) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2005.12.007 · Cited by 202 · see citing works
Colonic CD8 and γδ T-cell infiltration with epithelial damage in children with autism
Furlano, R. I., Anthony, A., Day, R., Brown, A., McGarvey, L., Thomson, M. A., Davies, S. E., Berelowitz, M., Forbes, A., Wakefield, A. J., et al. (2001) · The Journal of Pediatrics · doi:10.1067/mpd.2001.111323 · Cited by 195 · see citing works
Ashwood, P., Anthony, A., Pellicer, A. A., Torrente, F., Walker-Smith, J. A., & Wakefield, A. J. (2003) · Journal of Clinical Immunology · doi:10.1023/b:joci.0000010427.05143.bb · Cited by 197 · see citing works
Urinary p-cresol in autism spectrum disorder
Persico, A. M., & Napolioni, V. (2013) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2012.09.002 · Cited by 189 · see citing works
Urinary <i>p</i>-cresol is elevated in small children with severe autism spectrum disorder
Altieri, L., Neri, C., Sacco, R., Curatolo, P., Benvenuto, A., Muratori, F., Santocchi, E., Bravaccio, C., Lenti, C., Saccani, M., et al. (2011) · Biomarkers · doi:10.3109/1354750x.2010.548010 · Cited by 161 · see citing works
Can probiotics benefit children with autism spectrum disorders?
Navarro, F., Liu, Y., & Rhoads, J. M. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i46.10093 · Cited by 154 · see citing works
Autism and Schizophrenia: Intestinal Disorders
Cade, R., Privette, M., Fregly, M., Rowland, N., Sun, Z., Zele, V., Wagemaker, H., & Edelstein, C. (2000) · Nutritional Neuroscience · doi:10.1080/1028415x.2000.11747303 · Cited by 154 · see citing works
Microbiome and nutrition in autism spectrum disorder: Current knowledge and research needs
Berding, K., & Donovan, S. M. (2016) · Nutrition Reviews · doi:10.1093/nutrit/nuw048 · Cited by 146 · see citing works
Role of the Gut Microbiome in Autism Spectrum Disorders
Pulikkan, J., Mazumder, A., & Grace, T. (2019) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-030-05542-4_13 · Cited by 142 · see citing works
Gluten and casein free diets in autism: A study of the effects on food choice and nutrition
Cornish, E. (2002) · Journal of Human Nutrition and Dietetics · doi:10.1046/j.1365-277x.2002.00372.x · Cited by 137 · see citing works
Levy, S. E., Souders, M. C., Ittenbach, R. F., Giarelli, E., Mulberg, A. E., & Pinto-Martin, J. A. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.07.013 · Cited by 130 · see citing works
A preliminary study on nutritional status and intake in Chinese children with autism
Xia, W., Zhou, Y., Sun, C., Wang, J., & Wu, L. (2010) · European Journal of Pediatrics · doi:10.1007/s00431-010-1203-x · Cited by 124 · see citing works
Markers of celiac disease and gluten sensitivity in children with autism
Lau, N. M., Green, P. H. R., Taylor, A. K., Hellberg, D., Ajamian, M., Tan, C. Z., Kosofsky, B. E., Higgins, J. J., Rajadhyaksha, A. M., & Alaedini, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0066155 · Cited by 124 · see citing works
Lefter, R., Ciobica, A., Timofte, D., Stanciu, C., & Trifan, A. (2019) · Medicina · doi:10.3390/medicina56010011 · Cited by 120 · see citing works
Dargenio, V. N., Dargenio, C., Castellaneta, S., De Giacomo, A., Laguardia, M., Schettini, F., Francavilla, R., & Cristofori, F. (2023) · Nutrients · doi:10.3390/nu15071620 · Cited by 98 · see citing works
The relationship of autism and gluten
Buie, T. (2013) · Clinical Therapeutics · doi:10.1016/j.clinthera.2013.04.011 · Cited by 91 · see citing works
Julio-Pieper, M., Bravo, J. A., Aliaga, E., & Gotteland, M. (2014) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.12950 · Cited by 84 · see citing works
Systematic review of evidence to support the theory of psychobiotics
Romijn, A. R., & Rucklidge, J. J. (2015) · Nutrition Reviews · doi:10.1093/nutrit/nuv025 · Cited by 81 · see citing works
Nutritional management of (some) autism: a case for gluten- and casein-free diets?
Whiteley, P. (2015) · Proceedings of The Nutrition Society · doi:10.1017/s0029665114001475 · Cited by 52 · see citing works
Association Between Celiac Disease and Autism Spectrum Disorder: A Systematic Review
Quan, J., Panaccione, N., Jeong, J., Underwood, F. E., Coward, S., Windsor, J. W., Ronksley, P. E., Gidrewicz, D., deBruyn, J., Turner, J. M., et al. (2021) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0000000000003051 · Cited by 32 · see citing works
Wakefield′s "autistic enterocolitis" under the microscope
Deer, B. (2010) · BMJ · doi:10.1136/bmj.c1127 · Cited by 27 · see citing works
- Authors
- D'Eufemia, P., Celli, M., Finocchiaro, R., Pacifico, L., Viozzi, L., Zaccagnini, M., Cardi, E., & Giardini, O.
- Affiliations
- Sapienza University of Rome (IT)
- ORCID
- Venue
- Acta Paediatrica
- Publisher
- Wiley
- Published
- 1996-09
- Volume
- 85
- Issue
- 9
- Pages
- 1076-1079
- ISSN
- 0365-1436 (ISSN-L)
- 0803-5253
- 1651-2227
- OpenAlex
- W1978222253
- Cited by
- 416
- References
- 4
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 14 · 2023: 14 · 2022: 8 · 2021: 30 · 2020: 12 · 2019: 13 · 2018: 22 · 2017: 14 · 2016: 17 · 2015: 20 · 2014: 23 · 2013: 19 · 2012: 20
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Paediatrica (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- autism spectrum disorder, intestinal permeability, lactulose, mannitol, food peptides, behavioural abnormalities, children
- MeSH terms
- Adolescent, Autistic Disorder, Biological Transport, Child, Child, Preschool, Female, Gastrointestinal Diseases, Humans, Intestinal Absorption, Intestinal Mucosa, Lactulose, Male, Mannitol, Case-Control Studies
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