LAUSR

Objective Compelling evidence has confirmed that gut microbiota dysbiosis is involved in the development of autism spectrum disorder (ASD). Microbial-based therapies, including probiotics, may provide novel options for ASD management. This study aimed to investigate the alleviative effect of a probiotic strain, Bifidobacterium adolescentis (B. adolescentis) DM8504, on autistic-like behaviors in rats exposed to valproic acid (VPA). Methods Male offspring of VPA-exposed pregnant Sprague–Dawley rats treated with B. adolescentis DM8504 were subjected to behavioral tests. Fecal short-chain fatty acids (SCFAs) and microbiota composition were determined by targeted metabolomics and 16S rRNA gene sequencing, respectively. Microbial functional profiles were analyzed using the KEGG and COG pathway analyses. Results B. adolescentis DM8504 alleviated autistic-like behaviors in VPA-exposed rats, as evidenced by enhanced locomotor activity, exploratory behavior, sociability, spatial working memory, and depression relief. B. adolescentis DM8504 treatment significantly enhanced the fecal levels of acetic acid, butyric acid, isobutyric acid, propionic acid, and hexanoic acid, and restored the diversity of gut microbiota composition in VPA-exposed rats. Specifically, B. adolescentis DM8504 increased the abundance of gut bacterial species capable of producing SCFAs in VPA-exposed rats, including Bifidobacterium, Faecalibacterium, Eubacterium, and Lachnospiraceae_ NK4A136_group. In addition, microbial functional profile analysis showed that B. adolescentis DM8504 administration reversed the alterations in COG and KEGG pathways induced by VPA exposure. Conclusion These findings reveal that B. adolescentis DM8504 alleviates autistic-like behaviors in VPA-exposed rats through restoration of SCFA levels and enrichment of SCFA-producing bacteria, which indicate that well-defined B. adolescentis strains may have potential for the management of children with ASD in the future.