Safety and Efficacy of Prebiotic and Probiotic Supplementation in Decreasing Gastrointestinal and Behavioral Symptoms Among Children With Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

Background: Autism spectrum disorder (ASD) is characterized by persistent deficits in social communication and social interaction, which include deficits in social reciprocity, nonverbal communicative behaviors used for social interaction, and skills in developing, maintaining, and understanding relationships. Alongside these core symptoms of ASD, more frequently reported concurrent conditions are gastrointestinal (GI) problems and disturbances in sleep. GI problems (i.e., constipation, diarrhea, nausea and vomiting, abdominal bloating, stomachaches, and pain on evacuation) have been associated with more severe abnormalities in ASD patients. The mechanism underlying this is still poorly understood, but recent studies highlight the linkage of ASD to the gut-brain axis, genetic factors, gut microbiota, and immune responses. Thus, the possible therapeutic approach of rebalancing the gut microbiota for children with autism, through dietary and/or supplementation with probiotics have been advocated in recent years. This study aimed to synthesize available evidence in determining the safety and efficacy of supplementation of prebiotics and/or probiotics in decreasing gastrointestinal and behavioral symptoms among children with autism spectrum disorder. Method: A systematic review and meta-analysis of studies published between January 2013 until December 2022 was done to evaluate the use of prebiotic and/or probiotic versus placebo in children diagnosed with ASD. The studies were analyzed using random effects model with standard mean difference of outcome scores with regards to changes in gastrointestinal and behavioral symptoms. RevMan 5.4 was utilized in generating Forest plot for the interpretation of outcomes of interest. A p-value <0.05 were deemed statistically significant. Results: Six studies were included in the systematic review and four of which were included in the meta-analysis. The pooled mean difference showed that the mean final behavior score did not differ significantly between patients who were given probiotics and control (SDM=0.84, 95%CI=-1.09 to 2.76, I2=0.39). On the other hand, the mean change in behavior score was significantly greater in patients who were given probiotics (SDM=-1.37, 95%CI=-2.30 to -0.44, I2=0.004). Substantial heterogeneity was observed among studies (I2=88 to 98%). In four studies which assessed GI outcomes, only one study showed significant benefit of probiotics but the improvement was marginal. In terms of safety, there were no significant adverse events observed. Conclusion: This meta-analysis showed insufficient evidence of efficacy and safety of supplementation with prebiotic and/or probiotics in decreasing gastrointestinal and behavioral symptoms of children with ASD. Due to the substantial heterogeneity, inconsistency of findings, and small number of studies included in the analysis, further randomized clinical trials with larger sample size are recommended to confirm the clinical efficacy and safety of prebiotics and probiotics in treating gastrointestinal or behavioral symptoms in people with ASD.