Microbial community sequencing and host transcripts sequencing in the Shank3 mouse model of autism spectrum disorder

Shank genes are implicated in around 1% of people with autism and mice with Shank3 knock out mutations exhibit autism-like behaviours. Zinc deficiency and gastrointestinal problems can be common among people with autism, and zinc is a key element required for SHANK protein function and gut development. In Shank3Bmice, a supplementary zinc diet reverses autism behaviours. We hypothesise that dietary zinc may alter the gut microbiome, potentially affecting the gut-microbiome-brain axis, which may contribute to changes in autism-like behaviours. To test this, four types of gastrointestinal samples (ileum, caecum, colon, faecal) were collected from wild-type and knock-out Shank3B mice on either control or supplemented-zinc diets. Cage, genotype and zinc diet each contributed significantly to bacterial community variation (accounting for 12.8%, 3.9% and 2.3% of the variation, respectively). Fungal diversity differed significantly between wild-type and knock-out Shank3B-/- mice on the control zinc diet, and the fungal biota differed among gut locations. RNA-seq analysis of host (mouse) transcripts revealed differential expression of genes involved in host metabolism that may be regulated by the gut microbiota and genes involved in anti-microbial interactions. By utilising the Shank3B knock-out mouse model we were able to examine the influence of, and interactions between, dietary zinc and ASD-linked host genotype. These data broaden understanding of the gut microbiome in autism and pave the way towards potential microbial therapeutics for gastrointestinal problems in people with autism.