Probiotic Supplementation in Children and Adolescents with ADHD: A Systematic Review and Meta-Analysis of...

Dysregulation of the microbiota-gut-brain axis has been implicated in attention-deficit/hyperactivity disorder (ADHD), but randomized controlled trial evidence for probiotic supplementation remains inconsistent.

This systematic review and meta-analysis evaluated the effects of probiotic supplementation on ADHD-related clinical outcomes and emotional-behavioral outcomes in children and adolescents.

PubMed, Embase, Cochrane CENTRAL, Web of Science, PsycINFO, and EBSCO were searched from database inception to October 2025. Randomized controlled trials including participants under 18 years of age with DSM-defined ADHD were eligible. Pooled effects were calculated using standardized mean differences (SMDs) or mean differences (MDs) with 95% confidence intervals (CIs) under random-effects models.

Nine RCTs involving 482 participants were included, with intervention durations ranging from 8 to 12 weeks. In the broad exploratory synthesis of ADHD-related clinical outcomes, probiotic supplementation did not show a clear benefit (SMD = -0.25, 95% CI: -0.57 to 0.07; p = 0.131). Because this analysis combined conceptually heterogeneous instruments, greater interpretive weight was placed on domain-specific analyses. No clear effects were observed for more specific core symptom-related measures, including SNAP-IV inattention scores and CPT-derived attention-related performance measures. In domain-specific exploratory analyses, CPRS total scores showed a small reduction following probiotic supplementation (SMD = -0.33, 95% CI: -0.65 to -0.01; p = 0.041), whereas CBCL total scores did not show a statistically significant effect under the random-effects model (MD = -1.93, 95% CI: -6.30 to 2.44; p = 0.386). The SNAP-IV hyperactivity finding was statistically significant but was largely driven by a single study and should be interpreted cautiously.

Current 8-12-week RCT evidence does not demonstrate a clear benefit of probiotic supplementation for ADHD core symptom-related measures. However, exploratory findings suggest that probiotic supplementation may have potential for improving broad parent-reported emotional-behavioral outcomes, particularly CPRS-assessed behavioral symptoms. This potential benefit should be interpreted cautiously because it was based on a small number of heterogeneous trials and was not consistently supported by CBCL outcomes. Larger, rigorously designed trials are needed to confirm these broad parent-reported behavioral and emotional findings and clarify their clinical relevance.