title: Environment, dysbiosis, immunity and sex-specific susceptibility: a translational hypothesis for regressive autism pathogenesis.
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.
  
  
  CONCLUSIONS
  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.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mezzelani
authors.forename: Martina
authors.initials: M
authors.lastname: Landini
authors.forename: Francesco
authors.initials: F
authors.lastname: Facchiano
authors.forename: Maria Elisabetta
authors.initials: ME
authors.lastname: Raggi
authors.forename: Laura
authors.initials: L
authors.lastname: Villa
authors.forename: Massimo
authors.initials: M
authors.lastname: Molteni
authors.forename: Barbara
authors.initials: B
authors.lastname: De Santis
authors.forename: Carlo
authors.initials: C
authors.lastname: Brera
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Caroli
authors.forename: Luciano
authors.initials: L
authors.lastname: Milanesi
authors.forename: Anna
authors.initials: A
authors.lastname: Marabotti
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D001921:Brain / Q000254:growth & development* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D064806:Dysbiosis / Q000139:chemically induced / Q000276:immunology*; D004777:Environment; D005260:Female; D006801:Humans; D007223:Infant; D007422:Intestines / Q000254:growth & development / Q000382:microbiology / Q000473:pathology*; D008297:Male; D012307:Risk Factors; D012737:Sex Factors; D015262:Xenobiotics / Q000633:toxicity*
chemical_list: D015262:Xenobiotics
keywords: Environmental autism; Gut dysbiosis; Immune system; Sex bias; Xenobiotics