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Given that prebiotics have been shown to improve gut microbiota composition, gastrointestinal symptoms and select behaviors in autism spectrum disorder (ASD), we hypothesized that prebiotic supplementation would improve sociability, communication, and repetitive behaviors in a murine model of ASD. We also examined the effect of a synbiotic (probiotic + prebiotic). Juvenile male BTBR mice were randomized to: (1) control; (2) probiotic (1 × 10 10 CFU/d Lactobacillus reuteri RC-14 ® ; now known as Limosilactobacillus reuteri ); (3) prebiotic (10% oligofructose-enriched inulin); (4) prebiotic + probiotic (n = 12/group) administered through food for 3 weeks. Sociability, communication, repetitive behavior, intestinal permeability and gut microbiota were assessed. Probiotic and symbiotic treatments improved sociability (92 s and 70 s longer in stranger than empty chamber) and repetitive behaviors (50% lower frequency), whereas prebiotic intake worsened sociability (82 s less in stranger chamber) and increased the total time spent self-grooming (96 s vs. 80 s CTR), but improved communication variables (4.6 ms longer call duration and 4 s higher total syllable activity). Mice consuming probiotics or synbiotics had lower intestinal permeability (30% and 15% lower than CTR). Prebiotic, probiotic, and symbiotic treatments shifted gut microbiota to taxa associated with improved gut health. L.reuteri may help alleviate ASD behavioral symptom severity and improve gut health. The potential use of prebiotics in an ASD population warrants further research.

Prebiotic, Probiotic, and Synbiotic Consumption Alter Behavioral Variables and Intestinal Permeability and Microbiota in BTBR Mice