The therapeutic effects of probiotics on core and associated behavioral symptoms of autism spectrum disorders: a systematic review and meta-analysis

BACKGROUND: We aimed at investigating the efficacies of probiotics in alleviating the core and associated symptoms of autism spectrum disorder (ASD). METHODS: Randomized placebo-controlled trials were identified from major electronic databases from inception to Nov 2023. The outcomes of interests including improvements in the total and associated symptoms of ASD were quantitatively expressed as effect size (ES) based on standardized mean difference (SMD) with 95% confidence interval (CI). RESULTS: Ten studies with 522 participants (mean age = 8.11) were included in this meta-analysis. The primary results revealed significant improvement in total symptoms in the probiotics group compared with the controls (SMD = - 0.19, p = 0.03, ten studies, n = 522) but not the core symptoms (i.e., repetitive restricted behaviors, As affiliations 3 and 5 are same, we have deleted the duplicate affiliations and renumbered accordingly. Please check and confirm.problems with social behaviors/communication). Subgroup analyses demonstrated improvement in total symptoms in probiotics users relative to their controls only in studies using multiple-strain probiotics (SMD = - 0.26, p = 0.03, five studies, n = 288) but not studies using single-strain regimens. Secondary results showed improvement in adaptation (SMD = 0.37, p = 0.03, three studies, n = 139) and an improvement trend in anxiety symptoms in the probiotics group compared with controls (SMD = - 0.29, 95% CI - 0.60 to 0.02, p = 0.07, three studies, n = 163) but failed to demonstrate greater improvement in the former regarding symptoms of irritability/aggression, hyperactivity/impulsivity, inattention, and parental stress. CONCLUSIONS: Our study supported probiotics use against the overall behavioral symptoms of ASD, mainly in individuals receiving multiple-strain probiotics as supplements. However, our results showed that probiotics use was only associated with improvement in adaptation and perhaps anxiety, but not core symptoms, highlighting the impact of adaptation on quality of life rather than just the core symptoms. Nevertheless, the limited number of included trials warrants further large-scale clinical investigations.