title: Slow intestinal transit contributes to elevate urinary p-cresol level in Italian autistic children.
abstract: The uremic toxin p-cresol (4-methylphenol) is either of environmental origin or can be synthetized from tyrosine by cresol-producing bacteria present in the gut lumen. Elevated p-cresol amounts have been previously found in the urines of Italian and French autism spectrum disorder (ASD) children up until 8 years of age, and may be associated with autism severity or with the intensity of abnormal behaviors. This study aims to investigate the mechanism producing elevated urinary p-cresol in ASD. Urinary p-cresol levels were thus measured by High Performance Liquid Chromatography in a sample of 53 Italian ASD children assessed for (a) presence of Clostridium spp. strains in the gut by means of an in vitro fecal stool test and of Clostridium difficile-derived toxin A/B in the feces, (b) intestinal permeability using the lactulose/mannitol (LA/MA) test, (c) frequent use of antibiotics due to recurrent infections during the first 2 years of postnatal life, and (d) stool habits with the Bristol Stool Form Scale. Chronic constipation was the only variable significantly associated with total urinary p-cresol concentration (P < 0.05). No association was found with presence of Clostridium spp. in the gut flora (P = 0.92), augmented intestinal permeability (P = 0.18), or frequent use of antibiotics in early infancy (P = 0.47). No ASD child was found to carry C. difficile in the gut or to release toxin A/B in the feces. In conclusion, urinary p-cresol levels are elevated in young ASD children with increased intestinal transit time and chronic constipation. Autism Res 2016, 9: 752-759. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
authors.affiliation: Unit of Child and Adolescent NeuroPsychiatry, University Campus Bio-Medico, Rome, Italy.|Laboratory of Molecular Psychiatry and Neurogenetics, University Campus Bio-Medico, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gabriele
authors.affiliation: Unit of Child and Adolescent NeuroPsychiatry, University Campus Bio-Medico, Rome, Italy.|Laboratory of Molecular Psychiatry and Neurogenetics, University Campus Bio-Medico, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Sacco
authors.affiliation: Unit of Child and Adolescent NeuroPsychiatry, University Campus Bio-Medico, Rome, Italy.|Laboratory of Molecular Psychiatry and Neurogenetics, University Campus Bio-Medico, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Altieri
authors.affiliation: Department of Internal Medicine, University Tor Vergata, Rome, Italy.|Department of Experimental Neurosciences, I.R.C.C.S. "Fondazione S. Lucia", Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Neri
authors.affiliation: Department of Internal Medicine, University Tor Vergata, Rome, Italy.|Department of Experimental Neurosciences, I.R.C.C.S. "Fondazione S. Lucia", Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Urbani
authors.affiliation: Department of Translational Medical Science, University "Federico II", Naples, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Bravaccio
authors.affiliation: Department of Physical and Mental Health and Preventive Medicine, Second University of Naples, Naples, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Riccio
authors.affiliation: Department of Experimental Medicine, Second University of Naples, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Iovene
authors.affiliation: Department of Experimental Medicine, Second University of Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bombace
authors.affiliation: Department of Internal and Experimental Medicine Magrassi-Lanzara, Second University of Naples, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: De Magistris
authors.affiliation: Unit of Child and Adolescent NeuroPsychiatry, University Campus Bio-Medico, Rome, Italy.|Laboratory of Molecular Psychiatry and Neurogenetics, University Campus Bio-Medico, Rome, Italy.|Mafalda Luce Center for Pervasive Developmental Disorders, Milan, Italy.
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Persico
mesh_terms: D000067877:Autism Spectrum Disorder / Q000503:physiopathology*; D001321:Autistic Disorder; D002648:Child; D003408:Cresols / Q000652:urine*; D005243:Feces; D005772:Gastrointestinal Transit; D006801:Humans
chemical_list: D003408:Cresols; C032538:4-cresol
keywords: autism; autism spectrum disorder; biomarker; constipation; gut; intestinal transit; neurotoxicity; organic contaminants