Investigation of the Behavioral Impact of Lactobacillus Supplementation in Low Intellectual Disability Models of Autism in Drosophila

Drosophila melanogaster provides a powerful model for dissecting genetic and circuit-level mechanisms underlying neurodevelopmental disorders, including Autism Spectrum Disorder (ASD). However, most Drosophila ASD models rely on mutations orthologous to syndromic ASD in humans that co-occur with Intellectual Disability (ID), complicating behavioral assays and overlooking the nearly 50% of autistic individuals without ID. Emerging evidence across species implicates the gut-brain axis in ASD, implicating microbial elements in neural development and behavior. While well-studied in mammalian models, the role of the gut-brain axis in Drosophila remains largely underexplored. This project develops a Drosophila model to examine gut-brain interactions in ASD-associated behaviors without ID-like confounds. Candidate mutant fly lines in ASD-linked gene orthologs minimally associated with ID are screened with assays approximating core autistic traits before undergoing a Lactobacillus plantarum supplementation. Data revealed differences in behavior post-supplementation for atypical sensitivity testing, with sex playing a role, but no differences in repetitive behavior.