Aug 2026· Frontiers in Microbiology· Vol 17· 0 citations· 165 references
Medicine
TL;DR
Intervention strategies targeting the gut microbiota-such as probiotics/prebiotics supplementation, fecal microbiota transplantation (FMT), and gluten-free/casein-free diets-show promise in alleviating gastrointestinal symptoms and core behavioral deficits in children with ASD.
Abstract
Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by deficits in social interaction and the presence of repetitive, stereotyped behaviors, often accompanied by gastrointestinal symptoms. The prevalence of ASD is on the rise, and the lack of specific pharmacological treatments places a significant burden on families and society. However, the discovery of the microbiota-gut-brain axis (MGBA) offers new opportunities for research into ASD. The gut microbiota, a core component of the MGBA, engages in bidirectional communication with the central nervous system through neural, immune, and metabolic pathways. Dysregulation of the gut microbiota is closely associated with the pathogenesis and progression of ASD. Children with ASD often exhibit specific alterations in their gut microbiota, including an increased abundance of Firmicutes and Proteobacteria, a decreased abundance of Bacteroidaceae, and abnormalities in short-chain fatty acid metabolism. These alterations are associated with neurotransmitter imbalances and impaired intestinal barrier function, which are thought to subsequently contribute to neuroinflammation. Given these insights, intervention strategies targeting the gut microbiota-such as probiotics/prebiotics supplementation, fecal microbiota transplantation (FMT), and gluten-free/casein-free diets-show promise in alleviating gastrointestinal symptoms and core behavioral deficits in children with ASD. This narrative review synthesizes the fundamentals of the MGBA, critically examines the mechanisms linking gut microbiota to ASD, discusses recent advances in related treatments and their methodological limitations, and aims to provide insights for future research and the potential development of precise, microbiota-based interventions for ASD.
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by persistent social communication deficits and restricted, repetitive behaviors. Gastrointestinal symptoms are common and often correlate with symptom severity, implicating the microbiota–gut–brain axis as a potential mechanism linking gut dysbiosis with neurodevelopment through neural, immune, endocrine, and metabolic pathways. This review summarizes current evidence on alterations in the gut microbiota in ASD and critically examines whether these changes contribute to disease pathogenesis or represent secondary effects. It highlights recent advances in multi-kingdom microbiome profiling, metabolomics, mechanistic studies of neuroinflammation, and neurotransmitter signaling and considers major confounding factors, including diet, medication, and gastrointestinal comorbidities. Emerging studies emphasize microbial function over taxonomy. In the largest multi-kingdom analysis, 31 microbial and functional markers distinguished children with ASD from neurotypical controls with an area under the curve of 0.91, driven primarily by ubiquinol-7 and thiamine diphosphate biosynthesis pathways rather than individual taxa. Metabolomic and genetic studies suggest that microbial metabolites may mediate behavioral effects. Microbiota transfer therapy and fecal microbiota transplantation have demonstrated sustained improvements in gastrointestinal and behavioral outcomes, whereas probiotics and dietary interventions have produced inconsistent results. Although alterations in the gut microbiome are consistently observed in ASD, specific microbial signatures remain heterogeneous, and causality remains unproven. Functional microbial pathways appear more informative than taxonomic composition for biomarker discovery and therapeutic development. Future progress requires prospective birth cohorts, pre-diagnostic sampling, mechanistic validation, and adequately powered randomized trials before microbiome-based diagnostics and therapies can be translated into clinical practice.
Ahmed Kabrah, Saad Alghamdi, Anmar A. Khan et al.· Journal of Disability Resear...· 0 citations
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction, restricted interests, and repetitive behaviors. In addition to these core behavioral symptoms, gastrointestinal (GI) disorders are frequently reported, ranging from severe constipation to diarrhea. The links between ASD and gut dysfunction are further supported by alterations in gut microbiota composition and in bacteria‐derived metabolites. As the intrinsic nervous system of the digestive tract, the enteric nervous system (ENS) plays a central role in gut physiology by exerting neuronal control on several gut functions, including motility. Located at the interface between the gut microbiota and intestinal function, the ENS may play a key role in the GI symptoms associated with ASD, as demonstrated in several mouse models. This review aims to summarize the interconnected alterations of the gut microbiota and the ENS in ASD, with a particular focus on the microbiota‐derived mediators that are altered in ASD, among patients and animal models, and that may affect ENS development and function. By highlighting these interactions, this review seeks to provide new insights on the digestive pathophysiology of ASD, which may also contribute to the severity of behavioral symptoms.
Baptiste Ganachaud, M. J. Mendoza-León, Justine Marchix et al.· Autism Research· 0 citations
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social deficits and repetitive behaviors, often accompanied by gastrointestinal (GI) symptoms such as constipation, diarrhea, and abdominal pain. Emerging evidence highlights the gut-brain axis as a key pathway linking GI dysfunction to ASD pathophysiology. This review synthesizes current findings on the interplay among dietary patterns, gut microbiota dysbiosis, intestinal barrier dysfunction, and neuroimmune activation in ASD. We also discuss shared genetic vulnerabilities and environmental factors influencing both gut and brain function. Finally, we evaluate microbiota-targeted interventions, including probiotics and fecal microbiota transplantation, as potential therapeutic strategies. Understanding these mechanisms may inform personalized approaches to managing GI and behavioral symptoms in ASD.
Fei Fan, Bo Wang, Fei Han· Frontiers in Psychiatry· 0 citations
Growing evidence indicates that disruption of the microbiota-gut-brain (MGB) axis is a key factor in autism spectrum disorder (ASD), affecting neurodevelopment, neural circuit function, and behavior. This review synthesizes multidisciplinary data to clarify mechanistic links between the MGB axis and ASD and to evaluate microbiota-targeted therapeutic strategies. We conducted a narrative synthesis of clinical and translational studies, including human cohort and case-control investigations, animal models, multi-omics analyses, immune profiling, multimodal brain assessments (structural/functional MRI and transcriptomics), and interventional trials. Emphasis was placed on evidence of microbiota-brain associations, intervention outcomes, and methodological limitations. Key findings reveal that individuals with ASD commonly exhibit gut microbiome dysbiosis and altered metabolomic signatures that can influence central nervous system function; three core bidirectional signaling routes link gut microbes to brain outcomes-microbial metabolite production (e.g., short-chain fatty acids, tryptophan metabolites), immune-mediated pathways, and neuroendocrine-vagal communication. Accumulating data associate ASD-related microbial profiles with changes in brain structure, functional connectivity, and transcriptomic patterns, supporting a mechanistic role for the MGB axis in ASD phenotypes. Microbiota-targeted interventions show promising effects on gastrointestinal symptoms, metabolic biomarkers, and selected behavioral measures in small studies, but results are heterogeneous and current evidence is insufficient for widespread clinical application. Integrating multimodal neuroimaging with multi-omics and machine learning provides a promising framework to identify reproducible microbial-brain biomarkers for early detection, clinical subtyping, and stratified treatment. Key challenges include methodological heterogeneity, limited causal inference, small and heterogeneous cohorts, and ethical/safety concerns for pediatric interventions. The MGB axis is a plausible pathogenic mechanism and therapeutic target in ASD. Translating mechanistic insights into precision clinical applications requires standardized, multicenter, longitudinal deep-phenotyping studies that combine multimodal imaging, comprehensive multi-omics, rigorous randomized trials, and careful ethical oversight.
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.
Yan Zeng, Fengyang Wang, Silu Li et al.· Frontiers in Neuroscience· 0 citations
ASD has been associated with alterations of the microbiota-gut-brain axis, a bidirectional system that links gut microbiota to neural, endocrine, and immune pathways. Multi-omics studies indicate that most of the ASD affected individuals have lower levels of beneficial taxa, including Bifidobacterium, Lactobacillus gemelhinis, Faecalibacterium prausnitzii, and Roseburia species, and also enrichment with potentially pathogenic strains. Dysbiosis likely affects SCFA, especially butyrate, production. Butyrate acts via GPR41 and GPR43, which maintain the gut barrier and reduce inflammation. Lower butyrate and receptor activity can weaken the barrier, leading to systemic and neuroinflammation implicated in ASD. Effects of the microbiota on neurotransmission also seem pertinent, with alteration in tryptophan metabolism being able to affect central nervous system serotonin availability, and imbalance in GABA glutamate signaling potentially playing a role in excitatory inhibitory dysregulation. Immune crosstalk is paramount in these processes, as micro-bial products and SCFAs are able to influence microglial activity and brain-derived neurotrophic factor signaling with consequent impacts on synaptic plasticity and behavior. This narrative review synthesises societal momentum with current understanding and treatment approaches related to the microbiome of ASD. Probiotics, prebiotics, precision nutrition, and faecal microbiota transplanta-tion (FMT) have reported promising evidence of symptom reduction and, in some studies, behavior. Evidence is still mixed because of strain variation, dosing, delivery protocols, and follow-up. We delineate priorities for randomized, adequately powered experiments that incorporate longitudinal multi-omics, immune phenotyping, and standardized neurobehavioral assessments, while taking into account developmental timing and individual variation. Collectively, the current evidence suggests the gut-brain axis as a potential contributor to ASD biology and a potential target of therapy. Customized plans to rehabilitate SCFA production, enhance barrier function, and normalize neuro-immune and neurotransmitter pathways may augment current practice. Establishing causality and determining which patients benefit from which interventions when are the essential next steps.
Hamid Khan, Yumei Wang, Iqra Iftikhar et al.· Current Neuropharmacology· 0 citations