Research Papers

Summary:
Autism and ADHD share behavioural and biological features that make them useful for studying how gut microbes may interact with the developing brain. Both conditions commonly involve gastrointestinal symptoms, immune differences, metabolic changes and selective eating, suggesting that body‑wide systems may contribute to how symptoms present. Research on the gut-brain axis shows that gut microbes communicate with the brain through immune, endocrine and neural pathways. Although studies in autism have reported differences in gut microbiota compared with neurotypical peers, findings are inconsistent and no disorder‑specific microbial pattern has been identified. Immune-microbiota interactions may also influence neurodevelopment. To consolidate existing evidence, this study, a narrative review, examined human research on the gut-brain axis in autism and ADHD. The review summarised observational, cohort and interventional studies. Most autism studies were observational and reported links between symptom severity, gastrointestinal problems, intestinal permeability, immune activation and diet. Evidence in ADHD was limited and largely exploratory. The intervention studies which included interventions such as probiotics, microbiota transfer therapy and other gut‑directed approaches, showed consistent improvements in gastrointestinal symptoms but only modest effects on core autism features. Benefits were most apparent in individuals with significant gastrointestinal issues. Overall, this study suggests that microbiota‑related changes are better understood as factors that modify symptom expression, particularly in autism, rather than as direct causes of either condition. This interpretation highlights the need for future research to address remaining gaps, given how much is still unknown in this area.

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Abstract:
Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are increasingly conceptualized as multisystem neurodevelopmental conditions involving behavioral, gastrointestinal, immune, and metabolic alterations. The microbiota–gut–brain axis (MGBA) has been proposed as a key framework linking these systems, although evidence from human studies remains heterogeneous and inconclusive. We conducted a structured narrative review of pediatric human studies investigating the microbiota-gut-brain axis (MGBA) in ASD and ADHD, excluding preclinical and animal studies. PRISMA 2020 principles were used as a transparency framework to support reporting of study identification, screening, and eligibility. Observational, cohort, and interventional studies were synthesized with particular attention to study design, methodology, associations with standardized clinical scales, dietary factors, and therapeutic implications. Across ASD (n = 90), most studies were observational, predominantly cross-sectional or case-control in designs, reporting consistent associations between ASD symptom severity and gastrointestinal symptoms, intestinal permeability, immune activation, and dietary selectivity. Evidence in ADHD (n = 21) was substantially more limited and largely observational. Diet emerged as a major modulating and confounding factor in microbiota–behavior associations. Interventional studies involving probiotics, microbiota transfer therapy, and other gut-directed approaches showed more consistent improved gastrointestinal outcomes but showed modest and heterogeneous effects on core ASD symptoms, often limited to subgroups with prominent gastrointestinal comorbidities. To strengthen interpretation of interventional findings, randomized trial reports and non-randomized interventional studies were appraised according to study design, whereas the predominantly heterogeneous observational literature was interpreted narratively. Overall, this review suggests that MGBA alterations may be better conceptualized as modifiers of symptom expression, particularly in ASD and with only emerging relevance in ADHD, rather than as disorder-specific causal mechanisms. This interpretation underscores the need for stratified, longitudinal, and clinically informed research frameworks, in line with the focus of the present research topic.

Article Publication Date: 28/05/2026
DOI: 10.3389/frcha.2026.1835043

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