Integrated analysis of metabolome and microbiome in a mouse model of sodium valproate-induced autism.

Sodium valproate (SV) has been shown to induce autism in animal models. In this study, the SV method was used to establish a mouse model of autism, and anxiety-like behaviours and learning memory performance were evaluated by behavioural tests. The effects of SV on metabolic profiles and gut microbiota were assessed by integrating gas chromatography-mass spectrometry and 16S ribosomal RNA gene sequencing. Correlations between metabolites and gut microbiota were determined using Spearman correlation coefficient. Behavioral tests, including the three-chambered social assay, repetitive behaviors, open field test, elevated plus-maze test, and novel object recognition test, demonstrated that SV treatment exacerbated anxiety-like behaviors and impeded spatial learning and memory in mice. SV disrupted metabolic pathways in hippocampus, cortex, intestine, and serum, affecting primarily valine, leucine and isoleucine biosynthesis, glycerophospholipid metabolism and glutathione metabolism and so on. SV also altered gut microbiota at the genus level, decreasing the abundances of