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; Yanming Yang; Xiaoyi Fang; Liyang Liang; Hai Li; Zepeng Dong; Shilu Fan; Daqing Ma; Xue-Song Zhang; Huiliang Li; Yulong He; Ningning Li

doi:10.1016/j.xcrm.2024.101919

Gut microbial GABA imbalance emerges as a metabolic signature in mild autism spectrum disorder linked to overrepresented Escherichia

Cell Rep Med. 2025 Jan 7:101919. doi: 10.1016/j.xcrm.2024.101919. Online ahead of print.

Authors

Dilong Wang¹, Youheng Jiang², Jian Jiang³, Yihang Pan², Yanming Yang⁴, Xiaoyi Fang⁵, Liyang Liang⁶, Hai Li⁷, Zepeng Dong⁴, Shilu Fan⁸, Daqing Ma⁹, Xue-Song Zhang¹⁰, Huiliang Li¹¹, Yulong He¹², Ningning Li¹³

Affiliations

¹ Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518107, China; Department of Pediatrics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510000, China.
² Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518107, China; Center for Digestive Disease, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518107, China.
³ Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518107, China; Center for Clinical Molecular Medicine, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
⁴ Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518107, China.
⁵ Department of Neonatology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong 518107, China.
⁶ Department of Pediatrics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510000, China.
⁷ Neurorehabilitation Laboratory, Department of Rehabilitation Medicine, Shenzhen Hospital, Shenzhen, Guangdong 518107, China.
⁸ ARK Autism & Rehabilitation Institute, Taiyuan, Shanxi 030000, China.
⁹ Division of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, Chelsea and Westminster Hospital, London SW10 9NH, UK; Perioperative and Systems Medicine Laboratory, Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
¹⁰ Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ 08854, USA. Electronic address: xuesong.zhang@rutgers.edu.
¹¹ Wolfson Institute for Biomedical Research, Division of Medicine, Faculty of Medical Sciences, University College London, London WC1E 6AE, UK. Electronic address: huiliang.li@ucl.ac.uk.
¹² Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518107, China; Center for Digestive Disease, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518107, China. Electronic address: heyulong@mail.sysu.edu.cn.
¹³ Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518107, China; China-UK Institute for Frontier Science, Shenzhen 518107, China. Electronic address: linn29@mail.sysu.edu.cn.

PMID: 39809266
DOI: 10.1016/j.xcrm.2024.101919

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.

Keywords: Escherichia; autism; diagnostic biomarker; glutamate; gut microbiota; gut-brain axis; metabolome; multi-omics; neurotransmitter homeostasis; γ-aminobutyric acid.