Work

Gut-Derived Metabolic Imbalance in Autism Spectrum Disorder: Toward the Concept of a Metabolic Subtype

Year: 2026

Type: article

Abstract: Autism spectrum disorder (ASD) is highly heterogeneous in symptom onset and severity, comorbidities, and treatment responsiveness, challenging the notion of a single pathogenic mechanism. Increasing evidence indicates that some individuals with ASD exhibit prominent peripheral physiological alterations, including gastrointestinal (GI) dysfunction, gut microbial dysbiosis, immune imbalance, oxidative stress, and mitochondrial/energy metabolic vulnerability. In this context, gut-derived metabolites-particularly short-chain fatty acids (SCFAs)-have emerged as plausible modulators of the neurodevelopmental milieu through the expanded gut-immune-metabolic-brain axis. This review synthesizes: (i) SCFAs' biogenesis and physiological roles, (ii) context- and developmental stage-dependent effects, (iii) the clinical heterogeneity of reported microbiome and SCFA alterations in ASD, and (iv) propionate as a frequently discussed candidate signal and the interpretive boundaries of preclinical evidence. Human studies show substantial inter-study variability in SCFA alterations (increases, decreases, or no differences), influenced by factors such as sample type (stool vs. blood), GI symptoms, diet, medication exposure, and analytical variability. Accordingly, SCFAs should not be treated as universal ASD biomarkers but rather as context-dependent metabolic signals relevant under specific clinical and biological conditions. Building on this premise, we propose the conceptual framework of "metabolic ASD" representing a metabolically informed dimension of biological variability in which peripheral metabolic-immune perturbations may contribute to neurodevelopmental vulnerability. To avoid premature causal claims, we outline design requirements for future research, including stratified study designs, longitudinal cohorts, and integrative multi-layer analyses. Ultimately, metabolic ASD should be positioned as a testable precision medicine research framework rather than a universal etiological model.

Source: Nutrients

DOI: 10.3390/nu18091442

Authors: Ju Young Son, Yeyun Do, Jaemin Seo, Jeonghyun Choi

Institution: Daegu Haany University

Language: English

Topic: Gut microbiota and health

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499