Comparative Effectiveness of Probiotics, Prebiotics, and Synbiotics for Symptoms of Autism Spectrum Disorder: A Systematic Review and Network Meta-analysis

CONTEXT: Autism spectrum disorder (ASD) is characterized by impaired social interaction, communication deficits, and repetitive behaviors. Increasing evidence suggests that gut microbiota may be a potential therapeutic target. However, the relative efficacy of single-strain probiotics, multistrain probiotics, prebiotics, and synbiotics remains unclear. OBJECTIVE: This network meta-analysis aims to systematically compare the effectiveness of these microbiota-targeted interventions on ASD symptoms. DATA SOURCES: A systematic search of PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov was conducted up to June 20, 2025. DATA EXTRACTION: Randomized controlled trials (RCTs) assessing single-strain probiotics, multistrain probiotics, prebiotics, or synbiotics in individuals with ASD were included. The primary outcome was the improvement in deficits in core ASD symptoms, such as social communication and interaction and restricted and repetitive behaviors, which were assessed using standardized tools. DATA ANALYSIS: A Bayesian network meta-analysis with random-effects modeling was performed. Seventeen RCTs involving 904 participants were included. Synbiotics showed greater efficacy in improving ASD symptoms compared with placebo (standardized mean difference [SMD]: -1.90; 95% credible interval [CrI]: -2.66 to -1.06), prebiotics (SMD: -2.23; 95% CrI: -3.10 to -1.06), multistrain probiotics (SMD: -1.59; 95% CrI: -2.41 to -0.68), and single-strain probiotics (SMD: -1.52; 95% CrI: -2.40 to -0.60). The sensitivity analyses were generally consistent with the primary findings. CONCLUSION: Synbiotics appeared to demonstrate greater efficacy than probiotics, prebiotics, and placebo in improving behavioral symptoms of ASD. However, given the limited available evidence and modest sample sizes, this finding should be interpreted cautiously and considered preliminary. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration No. CRD420251078170.