PROJECT SUMMARY CDC statistics estimate that autism spectrum disorder (ASD) affects 1 in 36 children. ASD is characterized by stereotyped behaviors, social difficulties, and sensory hypo- and hyper-sensitivity. Hyperacusis is an example of this. Those with ASD more frequently suffer from auditory processing disorder and reduced hearing sensitivity as well. Most with ASD experience chronic gastrointestinal issues associated with increased intestinal permeability and microbial dysbiosis of the gut. Experimental studies in mouse models of ASD have demonstrated that treatments targeting gut microbiota can mitigate behavioral differences and synaptic alterations. Our preliminary findings demonstrate peripheral hearing dysfunction. Taken together, we hypothesize that gut dysbiosis contributes to hearing impairment in ASD. This proposal tests whether conventional gut microbiota can rescue hearing as well as social behaviors related to hearing. Specific aims evaluate 1) the effects of fecal microbial transfer on hearing and pathological markers at the adult stage and 2) the effects of microbiome shift in early life on hearing and related behaviors including ultrasonic vocalization and responses thereof. Findings will increase understanding of the role of gut microbiome in auditory plasticity as well as the role of hearing function in social behavioral differences characteristic of ASD. If beneficial, an implication is that conventional gut microbiota may represent a translational therapy.

PROJECT NARRATIVE Autism spectrum disorder is a common neurodevelopmental disorder affecting 1 in 36 children. Many with autism spectrum disorder suffer from gastrointestinal problems, and experimental studies have shown that treatments targeting the gut microbiome may lessen autism-associated behavioral differences. The goal of this proposal is to evaluate the role of the gut microbiome in hearing and behavioral differences found in an animal model of ASD.