gut metagenome from mouse feces Raw sequence reads. mouse gut metagenome

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting over 1% of the global population. Individuals with ASD often exhibit complex behavioral conditions, including significant social difficulties and repetitive behaviors. Here, we used a well-established ASD mouse model, induced by prenatal exposure to valproic acid (VPA), to study the physiological roles of Lactiplantibacillus plantarum PS128 in vivo. Overall, we established that PS128 selectively ameliorates behavioral abnormalities in social and spatial memory in VPA-induced ASD mice. Morphological examination of dendritic architecture further revealed that PS128 facilitated the restoration of dendritic arborization and spine density in the hippocampus and prefrontal cortex of ASD mice. Notably, PS128 was crucial for restoring oxytocin levels in the paraventricular nucleus and oxytocin receptor signaling in the hippocampus. Moreover, metagenomic sequencing results shows that the PS128 alters the gut microbiota composition and increases the abundance of Bifidobacterium spp., and PS128-induced changes in Bifidobacterium abundance positively correlated with PS128-induced behavioral improvements. Together, our results show that PS128 treatment can effectively ameliorate ASD-associated behaviors and reinstate oxytocin levels in VPA-induced mice, thereby providing a promising strategy for the future development of ASD therapeutics.