title: Hypothesis for a systems connectivity model of Autism Spectrum Disorder pathogenesis: links to gut bacteria, oxidative stress, and intestinal permeability.
abstract: Autism Spectrum Disorders are neurodevelopmental disorders with symptoms that include cognitive impairments, stereotyped behaviors, and impairments in social skills. The dramatic increase in incidence of autism in recent years has created an increased need to find effective treatments. This paper proposes a hypothesis for a systems model of the connections between Autism Spectrum Disorder pathogenesis routes observed in recent studies. A combination treatment option is proposed to combat multiple pathogenesis mechanisms at once. Autism has been cited as being linked to gastrointestinal symptoms and is thought to be caused by a combination of genetic predisposition and environmental factors. Neuroinflammation as a result of increased gastrointestinal permeability has been noted as being a likely cause of Autism Spectrum Disorders, with possible primary causes stemming from abnormal intestinal bacteria and/or sulfur metabolic deficiencies. Our pathogenesis model proposes a circular relationship: oxidative stress and sulfur metabolic deficiencies could cause changes in colonic bacterial composition; and environmental bacterial contaminants could lead to elevated oxidative stress in individuals. It would thus be a self-perpetuating process where treatment options with single targets would have short-lived effects. It is believed that bacterial toxins, oxidative stress and dietary allergens such as gluten could all lead to increased epithelial permeability. Therefore, we propose a combination treatment to combat intestinal permeability, abnormal bacteria and/or bacterial overgrowth, and sulfur metabolic deficiencies. It is our hope that the proposed model will inspire new studies in finding effective treatments for individuals with Autism Spectrum Disorders. We suggest possible future studies that may lend more credibility to the proposed model.
authors.affiliation: University of Delaware, Department of Chemical and Biomolecular Engineering, 150 Academy Street Newark, DE 19716, USA.
authors.forename: Colin A
authors.initials: CA
authors.lastname: Heberling
authors.forename: Prasad S
authors.initials: PS
authors.lastname: Dhurjati
authors.forename: Myron
authors.initials: M
authors.lastname: Sasser
mesh_terms: D002648:Child; D002659:Child Development Disorders, Pervasive / Q000503:physiopathology*; D006801:Humans; D007422:Intestines / Q000382:microbiology* / Q000503:physiopathology; D018384:Oxidative Stress; D010539:Permeability