Gut microbiome heterogeneity in autism spectrum disorder: immune-brain interfaces, behavioral phenotypes, and translational implications

Autism spectrum disorder (ASD) is clinically heterogeneous, and gastrointestinal symptoms, immune perturbation, microbial metabolites, and behavioral variation may intersect in biologically informative ways. The gut microbiome has therefore attracted substantial translational interest, although interpretation remains constrained by marked between-study heterogeneity, uneven phenotyping, and causal claims that often exceed the available evidence. This review brings together human cohort studies, family-aware analyses, multi-omics datasets, preclinical mechanistic work, controlled interventions, and selected registered trials. We followed a transparent targeted narrative-synthesis approach, drawing on PubMed/MEDLINE, Embase, Web of Science Core Collection, and ClinicalTrials.gov searches performed on 2 July 2026 (bibliographic date range, 1 January 2012 to 30 June 2026), predefined inclusion criteria, and an explicit distinction between mechanistic layers and evidentiary strength. Taken together, the evidence supports ASD microbiome heterogeneity as a framework for translational subgroup stratification, rather than as a basis for diagnostic or therapeutic claims. The revised framework outlines how host susceptibility, ecological organization, barrier-immune-metabolic relay biology, endophenotype expression, and translational responsiveness may be tested prospectively while accounting for diet, bowel phenotype, medication exposure, sex, developmental stage, and safety outcomes.