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

AI Summary

Gut-brain axis is a key mechanistic framework linking gut microbiota to neurodevelopment via endocrine, immune, neural and metabolic pathways.
ASD shows pronounced serotonergic and tryptophan-kynurenine dysregulation with heightened HPA axis responsiveness; short chain fatty acid findings are heterogeneous.
ADHD microbiome evidence is preliminary and mostly cross sectional; dopaminergic dysfunction lacks clear microbiota associations, requiring longitudinal multi-omic studies.

TL;DR (AI Generated)

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.

OBJECTIVE: 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.

Basic summary

AIMS Microbiol. 2026 Aug 25;12(3):548-563. doi: 10.3934/microbiol.2026024. eCollection 2026.

ABSTRACT

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

PMID:42859514 | PMC:PMC13652739 | DOI:10.3934/microbiol.2026024

Document this CPD