Correlation among gut microbiota, fecal metabolites and autism-like behavior in an adolescent valproic acid-induced rat autism model

Abstract

This study aims to understand the relationship between fecal metabolites and gut microbiota in an adolescent valproic acid-induced rat autism model (VPA-exposed offspring). We analyzed the fecal samples of VPA-exposed offspring using 16S rRNA gene sequencing and untargeted metabolomics. Autism-like behavior was evaluated by a three-chamber sociability test and a self-grooming test. Based on these data, we analyzed the association among fecal metabolites, gut microbiota and autism-like behavior. Behavioral tests showed that VPA-exposed offspring displayed typical autism-like behavior. Forty-nine named differential fecal metabolites and 14 enriched KEGG pathways were identified between the VPA and control groups. Five fecal metabolites may be used as characteristic metabolites. The richness and diversity of gut microbiota did not differ between the two groups, while the overall composition of gut microbiota was significantly different. Candidatus_Saccharimonas, Desulfovibrio, [Eubacterium]_xylanophilum_group and Ruminococcus_2 were the characteristic genera of VPA-exposed offspring. Correlation analysis revealed a tight relationship among gut microbiota, fecal metabolites and autistic behavior in VPA-exposed offspring. This study illustrates that specific alterations in gut microbiota and fecal metabolites may be regarded as characteristics of VPA-exposed offspring. The characteristic gut microbiota and fecal metabolites as well as their relationship may play a crucial role in autism-like behavior caused by prenatal exposure to VPA.