A probiotic therapy for Autism Spectrum Disorders?
Sarkis Mazmanian, PhD, Professor of Biology and Biological Sciences, California Institute of Technology
Although autism spectrum disorder (ASD) is defined by core behavioral impairments, gastrointestinal (GI) symptoms are commonly reported. Subsets of ASD individuals display dysbiosis of the gut microbiome, and some exhibit increased intestinal permeability. Here we demonstrate GI barrier defects and alterations in the composition of gut bacteria in a mouse model of an important ASD risk factor, maternal immune activation (MIA). Remarkably, oral treatment of MIA offspring with the human commensal Bacteroides fragilis corrects gut permeability, alters the intestinal microbiota and ameliorates autism-related defects in communicative, stereotypic, anxiety-like and sensorimotor behaviors. MIA offspring display an altered serum metabolomic profile, and B. fragilis modulates levels of several metabolites likely produced in the gut. Importantly, we show that treating naïve mice with a specific metabolite that is increased in MIA and restored by B. fragilis causes behavioral abnormalities, suggesting that gut bacterial effects on the host metabolome impact behavior. Taken together, these findings support a gut-microbiome-brain connection in ASD and identify a potential probiotic therapy for GI and behavioral symptoms of autism.