Bacteroides is increased in an autism cohort and induces autism-relevant behavioral changes in mice in a sex-dependent manner

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition which is defined by decreased social communication and the presence of repetitive or stereotypic behaviors. Recent evidence has suggested that the gut-brain axis may be important in neurodevelopment in general and may play a role in ASD in particular. Here, we present a study of the gut microbiome in 96 individuals diagnosed with ASD in Israel, compared to 42 neurotypical individuals. We determined differences in alpha and beta diversity in the microbiome of individuals with ASD and demonstrated that the phylum Bacteroidetes and genus Bacteroides were the most significantly over-represented in individuals with ASD. To understand the possible functional significance of these changes, we treated newborn mice with Bacteroides fragilis at birth. B. fragilis-treated male mice displayed social behavior dysfunction, increased repetitive behaviors, and gene expression dysregulation in the prefrontal cortex, while female mice did not display behavioral deficits. These findings suggest that overabundance of Bacteroides, particularly in early life, may have functional consequences for individuals with ASD.