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Alterations of the Intestinal Barrier in Patients With Autism Spectrum Disorders and in Their First-degree Relatives

de Magistris, Laura*; Familiari, Valeria*; Pascotto, Antonio†,#; Sapone, Anna*; Frolli, Alessandro; Iardino, Patrizia§; Carteni, Maria; De Rosa, Mario; Francavilla, Ruggiero; Riegler, Gabriele*; Militerni, Roberto; Bravaccio, Carmela||

Journal of Pediatric Gastroenterology and Nutrition: October 2010 - Volume 51 - Issue 4 - p 418–424
doi: 10.1097/MPG.0b013e3181dcc4a5
Original Articles: Gastroenterology

Objectives: Intestinal permeability (IPT) was investigated in patients with autism as well as in their first-degree relatives to investigate leaky gut hypothesis. Faecal calprotectin (FC) was also measured in patients with autism, either with or without gastrointestinal symptoms, and in their first-degree relatives.

Patients and Methods: IPT results, assessed by means of the lactulose/mannitol test, were compared with adult and child controls and with FC values.

Results: A high percentage of abnormal IPT values were found among patients with autism (36.7%) and their relatives (21.2%) compared with normal subjects (4.8%). Patients with autism on a reported gluten-casein–free diet had significantly lower IPT values compared with those who were on an unrestricted diet and controls. Gastrointestinal symptoms were present in 46.7% of children with autism: constipation (45.5%), diarrhoea (34.1%), and others (alternating diarrhoea/constipation, abdominal pain, etc: 15.9%). FC was elevated in 24.4% of patients with autism and in 11.6% of their relatives; it was not, however, correlated with abnormal IPT values.

Conclusions: The results obtained support the leaky gut hypothesis and indicate that measuring IPT could help to identify a subgroup of patients with autism who could benefit from a gluten-free diet. The IPT alterations found in first-degree relatives suggest the presence of an intestinal (tight-junction linked) hereditary factor in the families of subjects with autism.

*Department Magrassi-Lanzara, Gastroenterology, Italy

Department of Psychiatry, Neuropsychiatry, Dermatovenereology, Italy

Department of Experimental Medicine, Italy

§Department of Laboratory Medicine, Second University of Naples, Italy

||Department of Paediatrics, Federico II University of Naples, Italy

Clinica Pediatrica “B Trambusti,” University of Bari, Italy

#Fondazione Istituto Antoniano, Naples, Italy.

Received 11 November, 2009

Accepted 9 March, 2010

Address correspondence and reprint requests to Laura de Magistris, PhD, Second University of Naples, Department Magrassi-Lanzara, Gastroenterology, Piazza Miraglia 1-80132 Napoli, Italy (e-mail:

This research was supported in part with a grant from the Department Magrassi-Lanzara, Second University of Naples, Italy.

The present research was presented in poster form at Digestive Disease Week 2007 and 2008.

The authors report no conflicts of interest.

Copyright 2010 by ESPGHAN and NASPGHAN