Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are among the most prevalent neurodevelopmental conditions worldwide, yet the biological mechanisms driving their onset and phenotypic variability remain incompletely understood. The gut–brain axis (GBA), a bidirectional network linking intestinal microbial communities to central nervous system function through endocrine, immune, neural, and metabolic pathways, has emerged as a candidate mechanism through which environmental factors interact with genetic susceptibility to shape neurodevelopmental outcomes.
To systematically map the peer-reviewed evidence on gut microbiome-related mechanistic pathways in ASD and ADHD, we delineated features common to both disorders and identified areas of divergence and knowledge gaps requiring further investigation.
A scoping review was performed following the PRISMA Extension for the Scoping Reviews (PRISMA-ScR) framework. PubMed, Scopus, and Google Scholar were searched for peer-reviewed studies published January 2018 through March 2025. Studies addressing gut microbiome composition, GBA signaling, or microbiome-directed interventions in ASD or ADHD were eligible for inclusion. Extracted data were synthesized using inductive thematic analysis via Covidence software.
Forty-five studies satisfied the eligibility criteria. Inductive analysis produced five mechanistic themes: Endocrine dysregulation and microbial metabolite signaling; neuronal signaling and neurotransmitter modulation; immune activation and neuroinflammation; gene–microbiota–environment interactions; and microbiota-targeted interventions. Studies on both disorders demonstrated modifications involving taxa with short-chain-fatty-acid-producing capacity; however, findings were varied and did not prove a common reduction in butyrate production. ASD was marked by pronounced dysregulation of the serotonergic system and tryptophan–kynurenine pathway and increased hypothalamic-pituitary-adrenal (HPA) axis responsiveness. On the other hand, the results in ADHD were majorly cross-sectional or preliminary, and the widely-m recognized dopaminergic dysfunction in ADHD has not been associated to specific microbiota alterations to date.
Evidence demonstrates the GBA as a useful research conceptual for investigating ASD and ADHD, although the strength of mechanistic evidence differs substantially between the two disorders. Translating these insights into therapeutic strategies will require longitudinal, multi-omic research designs capable of establishing causality and enabling patient stratification for precision microbiome-based interventions.
Citation: Shifan Khanday, Afra Al Darmaki, Rokia Malahifci, Rima Alvavi, Sana Ahmed, Dina S. Nasr. Gut microbiota and the gut–brain axis in autism spectrum disorder and attention-deficit/hyperactivity disorder: A scoping review of shared and disorder-specific mechanistic pathways[J]. AIMS Microbiology, 2026, 12(3): 548-563. doi: 10.3934/microbiol.2026024
Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are among the most prevalent neurodevelopmental conditions worldwide, yet the biological mechanisms driving their onset and phenotypic variability remain incompletely understood. The gut–brain axis (GBA), a bidirectional network linking intestinal microbial communities to central nervous system function through endocrine, immune, neural, and metabolic pathways, has emerged as a candidate mechanism through which environmental factors interact with genetic susceptibility to shape neurodevelopmental outcomes.
To systematically map the peer-reviewed evidence on gut microbiome-related mechanistic pathways in ASD and ADHD, we delineated features common to both disorders and identified areas of divergence and knowledge gaps requiring further investigation.
A scoping review was performed following the PRISMA Extension for the Scoping Reviews (PRISMA-ScR) framework. PubMed, Scopus, and Google Scholar were searched for peer-reviewed studies published January 2018 through March 2025. Studies addressing gut microbiome composition, GBA signaling, or microbiome-directed interventions in ASD or ADHD were eligible for inclusion. Extracted data were synthesized using inductive thematic analysis via Covidence software.
Forty-five studies satisfied the eligibility criteria. Inductive analysis produced five mechanistic themes: Endocrine dysregulation and microbial metabolite signaling; neuronal signaling and neurotransmitter modulation; immune activation and neuroinflammation; gene–microbiota–environment interactions; and microbiota-targeted interventions. Studies on both disorders demonstrated modifications involving taxa with short-chain-fatty-acid-producing capacity; however, findings were varied and did not prove a common reduction in butyrate production. ASD was marked by pronounced dysregulation of the serotonergic system and tryptophan–kynurenine pathway and increased hypothalamic-pituitary-adrenal (HPA) axis responsiveness. On the other hand, the results in ADHD were majorly cross-sectional or preliminary, and the widely-m recognized dopaminergic dysfunction in ADHD has not been associated to specific microbiota alterations to date.
Evidence demonstrates the GBA as a useful research conceptual for investigating ASD and ADHD, although the strength of mechanistic evidence differs substantially between the two disorders. Translating these insights into therapeutic strategies will require longitudinal, multi-omic research designs capable of establishing causality and enabling patient stratification for precision microbiome-based interventions.
Autism spectrum disorder
Attention-deficit/hyperactivity disorder
Blood–brain barrier
Central nervous system
Excitatory–inhibitory
Fecal microbiota transplantation
γ-aminobutyric acid
Gut–brain axis
Hypothalamic-pituitary-adrenal
Interleukin-6
Interleukin-17
Lipopolysaccharide
Neurodevelopmental disorder
PRISMA extension for scoping reviews
Short-chain fatty acid
Tumor necrosis factor-alpha
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Figures(5) / Tables(1)
Shifan Khanday, Afra Al Darmaki, Rokia Malahifci, Rima Alvavi, Sana Ahmed, Dina S. Nasr. Gut microbiota and the gut–brain axis in autism spectrum disorder and attention-deficit/hyperactivity disorder: A scoping review of shared and disorder-specific mechanistic pathways[J]. AIMS Microbiology, 2026, 12(3): 548-563. doi: 10.3934/microbiol.2026024
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