L. reuteri RCT for children with ASD

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction, deficits in communication and the presence of restricted and repetitive behaviors. Despite its high prevalence and impact on affected individuals and their families, treatments that effectively improve the core symptoms of ASD remain elusive. Thus, the development of novel therapeutic strategies is an urgent priority. The gut-microbiota-brain axis is emerging as a potential new therapeutic target for the treatment of central nervous system disorders. More specifically, preclinical studies show that the commensal bacteria L. reuteri selectively reversed social deficits in several mouse models of ASD. However, whether L. reuteri improves social functioning in individuals with ASD remains unknown. In a double-blind, randomized, placebo-controlled trial, here we tested the effects of L. reuteri in children with ASD aged 2-8 years. There were no significant improvements in terms of overall autism severity (the primary outcome), however, there was a positive signal for improvements in social functioning (an important secondary outcome) that generalized across different measures (e.g., the Social Responsiveness Scale and the Social Adaptive Composite score of the Adaptive Behavior Assessment System). Consistent with the preclinical findings, the signal was specific to social functioning and interaction as the severity of restricted and repetitive behaviors, or other co-occurring problems (additional secondary outcomes) did not improve with the treatment. Moreover, consistent with the preclinical findings, treatment did not modulate the microbiome composition (primary outcome) or immune profile (additional secondary outcomes). Finally, we identified that only one of the two strains of L. reuteri in the human treatment may be driving the prosocial effect. Collectively, our findings indicate that L. reuteri treatment enhances social behavior in children with ASD, thereby warranting larger trials.