Wang, D; Jiang, Y; Jiang, J; Pan, Y; Yang, Y; Fang, X; Liang, L; ... Li, N; + view all Wang, D; Jiang, Y; Jiang, J; Pan, Y; Yang, Y; Fang, X; Liang, L; Li, H; Dong, Z; Fan, S; Ma, D; Zhang, XS; Li, H; He, Y; Li, N; - view fewer (2025) Gut microbial GABA imbalance emerges as a metabolic signature in mild autism spectrum disorder linked to overrepresented Escherichia. Cell Reports Medicine , 6 (1) , Article 101919. 10.1016/j.xcrm.2024.101919.

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Abstract

Gut microbiota (GM) alterations have been implicated in autism spectrum disorder (ASD), yet the specific functional architecture remains elusive. Here, employing multi-omics approaches, we investigate stool samples from two distinct cohorts comprising 203 children with mild ASD or typical development. In our screening cohort, regression-based analysis for metabolomic profiling identifies an elevated γ-aminobutyric acid (GABA) to glutamate (Glu) ratio as a metabolic signature of ASD, independent of age and gender. In the validating cohort, we affirm the GABA/Glu ratio as an ASD diagnostic indicator after adjusting for geography, age, gender, and specific food-consuming frequency. Integrated analysis of metabolomics, 16S rRNA sequencing, and metagenomics reveals a correlation between overrepresented Escherichia and disrupted GABA metabolism. Furthermore, we observe social behavioral impairments in weaning mice transplanted with E. coli, suggesting a potential link to ASD symptomatology. Collectively, these findings provide insights into potential diagnostic and therapeutic strategies aimed at evaluating and restoring gut microbial neurotransmitter homeostasis.

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