Gut microbiota dysbiosis in autism spectrum disorder: 10 years of progress on compositional alterations, metabolic/immune mechanisms, and therapeutic strategies

Abstract

Autism spectrum disorder (ASD) is a common neurodevelopmental condition frequently accompanied by gastrointestinal symptoms, pointing to a potential role of the gut microbiota–brain axis. To explore this connection, the present review synthesizes findings from studies published between 2016 and 2026, including observational studies, meta-analyses, animal experiments, and clinical trials, with the aim of characterizing gut microbiota alterations in ASD, elucidating underlying mechanisms, and evaluating emerging therapeutic strategies. Across diverse populations, the most consistent microbial signatures in ASD include reduced abundances of Bifidobacterium and Akkermansia muciniphila, together with increased abundances of Clostridium, Bacteroides, and Escherichia–Shigella; however, geographic, age-, and sex-specific variations exist. In addition to bacterial changes, the gut virome and mycobiome are also perturbed, as evidenced by enrichment of Candida albicans and Clostridium phages. Mechanistically, these alterations are linked to reduced short-chain fatty acids (especially butyrate), disrupted tryptophan–serotonin metabolism, and elevated neuroinflammatory cytokines (e.g., TNF-α, IL-6). Causal evidence from animal models using fecal microbiota transplantation further demonstrates that ASD microbiota can directly induce autistic-like behaviors. Building on this causal link, early-phase clinical trials indicate that fecal microbiota transplantation, probiotics, prebiotics, and dietary interventions (e.g., ketogenic diet) can improve both gastrointestinal and behavioral symptoms, although larger double-blind, placebo-controlled trials are needed to confirm efficacy. Furthermore, multi-omics integration and host epigenetic signatures show promise for developing non-invasive diagnostic biomarkers. In conclusion, gut dysbiosis plays a causal role in ASD pathophysiology, and microbiome-based interventions represent a rational and potentially transformative therapeutic avenue.