title: Prenatal and Postnatal Epigenetic Programming: Implications for GI, Immune, and Neuronal Function in Autism.
abstract: Although autism is first and foremost a disorder of the central nervous system, comorbid dysfunction of the gastrointestinal (GI) and immune systems is common, suggesting that all three systems may be affected by common molecular mechanisms. Substantial systemic deficits in the antioxidant glutathione and its precursor, cysteine, have been documented in autism in association with oxidative stress and impaired methylation. DNA and histone methylation provide epigenetic regulation of gene expression during prenatal and postnatal development. Prenatal epigenetic programming (PrEP) can be affected by the maternal metabolic and nutritional environment, whereas postnatal epigenetic programming (PEP) importantly depends upon nutritional support provided through the GI tract. Cysteine absorption from the GI tract is a crucial determinant of antioxidant capacity, and systemic deficits of glutathione and cysteine in autism are likely to reflect impaired cysteine absorption. Excitatory amino acid transporter 3 (EAAT3) provides cysteine uptake for GI epithelial, neuronal, and immune cells, and its activity is decreased during oxidative stress. Based upon these observations, we propose that neurodevelopmental, GI, and immune aspects of autism each reflect manifestations of inadequate antioxidant capacity, secondary to impaired cysteine uptake by the GI tract. Genetic and environmental factors that adversely affect antioxidant capacity can disrupt PrEP and/or PEP, increasing vulnerability to autism.
authors.affiliation: Department of Food Science and Nutrition, Sultan Qaboos University, Alkoudh 123, Muscat, Oman.
authors.forename: Mostafa I
authors.initials: MI
authors.lastname: Waly
authors.forename: Mady
authors.initials: M
authors.lastname: Hornig
authors.forename: Malav
authors.initials: M
authors.lastname: Trivedi
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Hodgson
authors.forename: Radhika
authors.initials: R
authors.lastname: Kini
authors.forename: Akio
authors.initials: A
authors.lastname: Ohta
authors.forename: Richard
authors.initials: R
authors.lastname: Deth