Psychobiotics in pediatric autism spectrum disorder: A systematic review of efficacy, mechanisms, and clinical translation

Abstract

BACKGROUND

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition frequently associated with gastrointestinal (GI) disturbances and alterations in gut microbiota composition. Increasing evidence suggests that the microbiota-gut-brain axis may play a role in the pathophysiology of ASD, raising interest in microbiome-targeted therapies, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT). However, the clinical effectiveness and mechanisms of these interventions remain incompletely understood due to heterogeneous study designs and variable outcomes across trials.

AIM

To systematically evaluate the clinical efficacy and mechanistic implications of psychobiotic interventions, including probiotics, prebiotics, synbiotics, and FMT, in children with ASD.

METHODS

We conducted this systematic review in accordance with PRISMA 2020 guidelines. We also followed the methodological recommendations of the Cochrane Handbook. We searched different electronic databases, including PubMed/MEDLINE, EMBASE, Web of Science, PsycINFO, CENTRAL, and CINAHL, from inception till February 2026. We included eligible randomized controlled trials, controlled clinical trials, cohort studies, and pre–post intervention studies evaluating psychobiotic therapies in children and adolescents (≤ 18 years) with ASD. The main outcomes were: (1) Changes in severity as assessed by a broad-spectrum measure of ASD symptomatology at the 3-month follow-up; and (2) Variation of core symptoms, based on validated behavioral scales, including the Autism Diagnostic Observation Schedule, the Childhood Autism Rating Scale (CARS), and the Social Responsiveness Scale (SRS). We measured the severity of GI symptoms, microbiome composition, biologicals, and safety as secondary outcomes. Risk of bias was determined with Risk of Bias tool version 2 and Risk of Bias in Non-randomized Studies of Interventions tools. Meta-analysis using random-effects models was conducted where appropriate.

RESULTS

We reviewed 35 clinical studies that examined microbiome-targeted therapies in children with ASD. Overall, probiotics were associated with obvious improvements in GI symptoms and smaller, but noticeable, improvements in behavioral outcomes, although the benefits varied depending on the probiotic strains used, treatment duration, and whether children had GI problems at baseline. When data from selected probiotic studies were pooled, a moderate-to-large overall benefit was observed for GI symptom severity. Prebiotic supplementation mainly benefited gut function and microbial metabolic activity, with little and inconsistent impact on core autism symptoms. Synbiotic approaches-which combine probiotics with fermentable substrates-produced broader effects on the gut microbiome and were linked to modest improvements in both GI and behavioral symptoms. We observed that FMT showed the strongest overall effects among all microbiome-based interventions. Using quantitative analyses, we observed marked improvements in GI symptoms (GI SRS pooled SMD -2.71), along with a significant decrease in key behavioral measures, including social responsiveness (SRS pooled SMD -4.06), aberrant behavior (Aberrant Behavior Checklist -3.00), and overall autism severity (CARS -1.60). However, the strength of this evidence is tempered by the fact that many FMT studies were open-label or non-randomized, which limits confidence in the robustness of these findings. Across all microbiome-targeted therapies, benefits were most consistently observed for GI outcomes, whereas improvements in core ASD symptoms were more variable and less predictable.

CONCLUSION

Microbiome-targeted therapies are a promising adjunctive strategy in managing children with ASD, especially for associated GI disorders. Probiotics and prebiotics provided the most reliable benefits for GI symptoms, while synbiotics may offer broader microbiome modulation, and FMT has the greatest observed improvements in both GI and behavioral outcomes. However, considerable heterogeneity across studies and limited high-quality randomized trials highlight the need for large, well-designed clinical trials with standardized intervention protocols to clarify clinical efficacy and guide future therapeutic recommendations.

Keywords: Autism spectrum disorder; Psychobiotics; Probiotics; Prebiotics; Synbiotics; Fecal microbiota transplantation; Gut–brain axis; Children

Core Tip: Microbiome-targeted therapies are emerging as promising adjunctive strategies for children with autism spectrum disorder, particularly in those with co-existing gastrointestinal disorders. We observed from this systematic review that probiotics and prebiotics consistently improve gastrointestinal symptom severity, while synbiotics may provide broader modulation of gut microbial ecology. Fecal microbiota transplantation induced the largest observed improvements in both gastrointestinal outcomes and selected behavioral domains, although current evidence is limited by small sample sizes and methodological heterogeneity. These findings support strong evidence that the microbiota-gut-brain axis is a biologically reasonable therapeutic target and highlight the need for large, well-designed randomized trials.