Abstract
Abstract
Background
The microbiota-gut-brain axis provides a biologically plausible framework for bidirectional communication between intestinal microorganisms and the central nervous system. Human studies have reported gut microbiota differences in autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and schizophrenia, but the reproducibility and clinical meaning of these observations remain uncertain.
Objective
To critically summarize human evidence on gut microbiota composition in ASD, ADHD, and schizophrenia, and to assess clinical evidence for probiotic and synbiotic formulations and fecal microbiota transplantation (FMT) in these disorders.
Methods
A focused narrative review was conducted using PubMed and supplementary Google Scholar searches. Publications from 1 January 2012 to 31 December 2024 were considered, and the final search update was completed on 28 February 2025. Forty-two publications were purposively selected and synthesized; original human studies were prioritized whenever available. Evidence was interpreted with attention to study design, sample size, medication exposure, diet, gastrointestinal symptoms, stool characteristics, sequencing and bioinformatics methods, outcome selection, safety reporting, and risk of reverse causality. Because this was a narrative rather than a systematic review, no PRISMA flow diagram, duplicate independent screening, formal study-level risk-of-bias instrument, or new quantitative pooling was used.
Results
Across all three disorders, individual studies and meta-analyses report group-level microbiota differences, but no reproducible disorder-specific microbial signature has been established. In ASD, dietary selectivity, gastrointestinal symptoms, and stool consistency explain an important proportion of reported associations. ADHD studies are generally small and yield conflicting diversity and taxonomic findings. In schizophrenia, associations are influenced by antipsychotic exposure, metabolic status, smoking, diet, and illness chronicity. Controlled trials and meta-analyses have not shown consistent improvement in core symptoms with probiotic or synbiotic products. Early uncontrolled microbiota-transfer studies in ASD suggested possible benefits, but a 2024 randomized placebo-controlled FMT trial did not demonstrate improvement in its primary clinical outcome. Evidence for FMT in ADHD is limited to a case report, and no controlled human efficacy evidence was identified for schizophrenia. FMT carries infectious, procedural, and uncertain long-term risks.
Conclusions
Gut microbiota differences in ASD, ADHD, and schizophrenia should currently be regarded as associated features rather than established causes, diagnostic biomarkers, or validated therapeutic targets. Routine microbiome testing, probiotics or synbiotics for core symptoms, and FMT cannot be recommended as standard treatments for these disorders. Future studies require longitudinal designs, careful control of diet and medication, standardized laboratory methods, preregistered clinical outcomes, adequate power, external validation, and systematic safety monitoring.