Critical roles for microbiota-mediated regulation of Th17 responses in a maternal immune activation model of autism

Abstract

Abstract Recent studies suggest that autism is often associated with altered microbiota composition and gastrointestinal inflammation. This work has led to growing speculation of a potential role for the microbiome in autism spectrum disorder (ASD). However, how microbiota diversity mechanistically influences the development of autistic phenotypes has not been studied in great detail to date. To formally investigate this, we evaluated how environmentally induced changes in gut microbiota landscape influence the incidence and severity of MIA-induced neurodevelopmental disorders. Herein, we report critical roles for prenatal microbiota composition in the development of behavioral abnormalities in a MIA mouse model of autism. Mechanistically, we show that microflora-dependent calibration of the immune response underlies the effects of the microbiome on inflammation-induced ASD-like phenotypes. Specifically, we find that neutralization of IL-17a ameliorates the ability of the microbiome to affect the development of autism-related behaviors. Our results identify the immune system as a link between gut microbiota and the brain in neurodevelopmental disorders, and suggest that targeting the microbiome and maternal immune responses during gestation may offer strategies to limit autism development in at-risk pregnancies.