Gut microbial GABA imbalance emerges as a metabolic signature in mild autism spectrum disorder linked to overrepresented Escherichia
Dilong Wang, Youheng Jiang, Jian Jiang, Yihang Pan, Yuan‐Han Yang, Xiaoyi Fang, Liyang Liang, Hai Li, Hai Li, Zepeng Dong, Shilu Fan, Daqing Ma, Xue‐Song Zhang, Huiliang Li, Huiliang Li, Yulong He, Ningning Li
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. • Features of imbalanced gut microbial GABA metabolism in preschool children with mild ASD • Microbial GABA/glutamate ratio is potentially an independent marker for ASD diagnosis • Overrepresentation of Escherichia is associated with abnormal GABA metabolism in ASD • Simulated overgrowth of E. coli potentiates social deficits in mice Wang et al. find an elevated gut microbial GABA/glutamate ratio in children with ASD, establishing it as a marker associated with ASD diagnosis. They elucidate that abnormal GABA metabolism is linked to the overrepresentation of Escherichia in the gut. These findings provide insights into strategies aiming at restoring neurotransmitter homeostasis in ASD.