Metabolic Association Between the Gut–Brain Axis in Autism Spectrum Disorders

  • María Andrea Delgado
  • Adriana Fochesato
  • Luis Isaías Juncos
  • Pascual Ángel Gargiulo


Autism spectrum disorder (ASD) is a severe, complex neurodevelopmental disorder, characterized by impairments in social interaction and communication with restricted and stereotyped behavior patterns. ASD symptoms result from a complex interaction between genetic and environment factors. Food intolerances, allergies, altered intestinal permeability (leaky gut), immune dysregulation, neuroinflammation and oxidative stress may trigger ASD symptoms. ASD patients have shown increased urinary levels of β-casomorphin and gliadorphin peptides produced by incomplete digestion of gluten proteins and milk casein. “Leaky gut” may facilitate the transport of these peptides into the central nervous system (CNS) inducing direct “opioid activity” and thus affecting neurotransmission. ASD patients on gluten and/or casein-free diet have shown improvement in most behavior and cognitive scores. Immune dysregulation leads to a neuroinflammatory response that correlates between immune dysfunction with behavioral and cognitive impairments in ASD patients. Genetic variants of the MET gene (7q31.2) are risk factors for ASD. The MET receptor participates in brain cortex and cerebellum development and in gastrointestinal and immunological functions. A high percentage of ASD children have shown non-celiac gluten sensitivity, an immune reaction against gluten in subjects not affected with celiac disease with prominent mucosal eosinophil infiltration and increased blood eosinophilia. ASD patients have shown alterations in brain anatomy involved in language and social interaction skills, correlating with specific aspects of ASD symptoms. ASD behavior results from abnormal interactions between the opioid system and various pathways together with anatomical alterations in the CNS. Individualized diagnosis and prognostic predictions should provide effective personalized therapies in ASD patients.


Autism spectrum disorders Opioid peptides Leaky gut Genetics Immune dysregulation 


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • María Andrea Delgado
    • 1
  • Adriana Fochesato
    • 1
  • Luis Isaías Juncos
    • 1
  • Pascual Ángel Gargiulo
    • 2
  1. 1.Fundación J Robert CadeCórdobaArgentina
  2. 2.Laboratorio de Neurociencias y Psicología Experimental, Área de Farmacología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, CONICETMendozaArgentina

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