Synbiotic combination of 2'-fucosyllactose andmitigates neurodevelopmental disorders and ASD-like behaviors induced by valproic acid.

Abstract

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() outperformed that of 2'-FL and() 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 andimproved gut morphology and barrier integrity, reduced gut inflammation, and optimized the gut microbiota structure by increasing the abundance ofand, 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 andsupports gut microbiota homeostasis, enhances fecal SCFA levels, and mitigates neurodevelopmental abnormalities in ASD mice.