Environment, dysbiosis, immunity and sex-specific susceptibility: A translational hypothesis for regressive autism pathogenesis

Alessandra Mezzelani, Martina Landini, Francesco Facchiano, Maria Elisabetta Raggi, Laura Villa, Massimo Molteni, Barbara De Santis, Carlo Brera, Anna Maria Caroli, Luciano Milanesi, Anna Marabotti

Research output: Contribution to journalArticle

Abstract

Background: Autism is an increasing neurodevelopmental disease that appears by 3 years of age, has genetic and/or environmental etiology, and often shows comorbid situations, such as gastrointestinal (GI) disorders. Autism has also a striking sex-bias, not fully genetically explainable. Objective: Our goal was to explain how and in which predisposing conditions some compounds can impair neurodevelopment, why this occurs in the first years of age, and, primarily, why more in males than females. Methods: We reviewed articles regarding the genetic and environmental etiology of autism and toxins effects on animal models selected from PubMed and databases about autism and toxicology. Discussion: Our hypothesis proposes that in the first year of life, the decreasing of maternal immune protection and child immune-system immaturity create an immune vulnerability to infection diseases that, especially if treated with antibiotics, could facilitate dysbiosis and GI disorders. This condition triggers a vicious circle between immune system impairment and increasing dysbiosis that leads to leaky gut and neurochemical compounds and/or neurotoxic xenobiotics production and absorption. This alteration affects the ‘gut–brain axis’ communication that connects gut with central nervous system via immune system. Thus, metabolic pathways impaired in autistic children can be affected by genetic alterations or by environment–xenobiotics interference. In addition, in animal models many xenobiotics exert their neurotoxicity in a sex-dependent manner. Conclusions: We integrate fragmented and multi-disciplinary information in a unique hypothesis and first disclose a possible environmental origin for the imbalance of male:female distribution of autism, reinforcing the idea that exogenous factors are related to the recent rise of this disease.

Original languageEnglish
Pages (from-to)145-161
Number of pages17
JournalNutritional Neuroscience
Volume18
Issue number4
DOIs
Publication statusPublished - May 1 2015

Keywords

  • Environmental autism
  • Gut dysbiosis
  • Immune system
  • Sex bias
  • Xenobiotics

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics
  • Neuroscience(all)

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    Mezzelani, A., Landini, M., Facchiano, F., Raggi, M. E., Villa, L., Molteni, M., De Santis, B., Brera, C., Caroli, A. M., Milanesi, L., & Marabotti, A. (2015). Environment, dysbiosis, immunity and sex-specific susceptibility: A translational hypothesis for regressive autism pathogenesis. Nutritional Neuroscience, 18(4), 145-161. https://doi.org/10.1179/1476830513Y.0000000108