Synbiotic combination of 2′-fucosyllactose and Bifidobacterium mitigates neurodevelopmental disorders and ASD-like behaviors induced by valproic acid†

Autism spectrum disorder (ASD) is a group of heterogeneous neurodevelopmental disorders characterized by social deficits and repetitive behaviors. Increasing evidence suggests that the gut microbiota influences neurodevelopment and behavior. In this study, we established an ASD model by administering valproic acid (VPA) to pregnant females, with male offspring receiving a daily synbiotic intervention for four weeks post-weaning. The results indicate that the synbiotic combination of 2′-Fucosyllactose (2′-FL) and Bifidobacterium animalis subsp. lactis BB-12 (BB-12) outperformed that of 2′-FL and Lactobacillus paracasei L9300BH (L9300BH) in alleviating social deficits, repetitive behaviors, neuronal damage, and dysregulated expression of social-related genes and neuroinflammatory markers in ASD mice. Additionally, the intervention with 2′-FL and BB-12 improved gut morphology and barrier integrity, reduced gut inflammation, and optimized the gut microbiota structure by increasing the abundance of Bifidobacteria and Akkermansia, known producers of short-chain fatty acids (SCFAs). Notably, levels of acetate, propionate, and butyrate were significantly elevated in fecal samples. In summary, the synbiotic combination of 2′-FL and BB-12 supports gut microbiota homeostasis, enhances fecal SCFA levels, and mitigates neurodevelopmental abnormalities in ASD mice.