Probiotics and prebiotics alleviate behavioral deficits, inflammatory response, and gut dysbiosis in prenatal VPA-induced rodent model of autism

Autism spectrum disorders are neuropsychiatric conditions characterized by social interaction and communi-cation disorders and repetitive stereotypical behaviors. These disorders are also accompanied by an inflamma-tory status. Bidirectional communication between microbiome, gut, and brain has been discovered as a major mechanism influencing core symptoms and biomarkers of autism. Therefore, the modulation of the gut micro -biota in autism has recently attracted interest. In this study, probiotic-and prebiotic-mediated modulation of the gut microbiota was compared in terms of different symptoms and findings in an experimental autism model. Valproic acid (VPA) (500 mg/kg) was administered to Wistar rats (on prenatal day 12.5) to induce autistic-like behaviors. Based on the supply of probiotics and prebiotics, animals were grouped as control (saline), autistic -like (prenatal VPA), probiotic (prenatal VPA + 22.5 x 109 cfu/day probiotic), prebiotic (prenatal VPA + 100 mg/day prebiotic), and combined treatment (prenatal VPA + 22.5 x 109 cfu/day probiotic + 100 mg/day prebiotic). After the treatment process, behavioral tests (social behaviors, anxiety, stereotypical behavior, sensorimotor gating, and behavioral despair) and biochemical analyses (serum and brain tissue) were conducted, and the quantities of some phyla and genera were determined in stool samples. Significant positive effects of probiotic and combined treatments were observed on the sociability, social interaction, and anxiety parameters. In addition, all three treatments had positive effects on stereotypical behavior. However, the treatments did not affect sensorimotor gating deficits and behavioral despair. Further, probiotic treatment reversed the VPA-induced increase and decrease in serum IL-6 and IL-10 levels, respectively. Combined treatment also signifi-cantly increased the IL-10 levels. Prenatal VPA exposure decreased 5-hydroxytryptamine (5-HT) levels in the prefrontal cortex of the brain; however, combined treatment reversed this decrease. Prenatal VPA exposure also caused a decrease in Bacteroidetes/Firmicutes ratio in the gut microbiota, while the probiotic treatment significantly increased this ratio. These findings indicate that probiotic-and prebiotic-mediated microbial modulation may represent a new therapeutic approach to alleviate autistic-like symptoms.

Automated summary

This study compared the effects of probiotics and prebiotics on the modulation of gut microbiota in an experimental autism model. The results showed that probiotic and combined treatments had significant positive effects on sociability, social interaction, and anxiety parameters, but had no significant impact on stereotypical behavior. Furthermore, probiotic treatment reversed the changes in serum IL-6 and IL-10 levels induced by VPA, while combined treatment significantly increased IL-10 levels.