Researchers identify imbalance in GABA/glutamate ratio in gut microbiomes of preschool children with mild autism

The gut microbiome plays a role in the metabolism and function of the neurotransmitters GABA and glutamate, and a study by researchers in China indicates that an altered GABA-to-glutamate ratio in the gut microbiomes of autistic children—possibly caused by an overabundance of one genus of microbes—may be a marker for autism.

Dilong Wang and colleagues analyzed stool samples from 203 preschool-aged children with mild ASD or typical development. In two separate groups—an initial screening group and a validating group—they detected an elevated ratio of GABA compared to glutamate in the autistic children. They note that the findings in the screening group were independent of age and gender, while the validating group came from a geographically diverse population, and the results for this group were adjusted for age, gender, and diet.

The researchers add, “We observed an overall reduction in gut microbiota functionality… in autistic subjects with an I’m balanced GABA/glutamate metabolism. This aligns with growing evidence pointing to a suboptimal, inefficient state of ASD-linked gut microbiota, including impaired detoxifying ability, decreased neurotransmitter synthesis, and delayed microbiota maturity.”

Further analysis by the researchers showed a correlation between disrupted GABA metabolism and an overabundance of the Escherichia genus of microbes. Moreover, when the team transplanted Escherichia coli into weaning mice, the mice exhibited social impairments. The researchers say their findings add to those of other studies pointing to a potentially significant role of Escherichia in ASD.

They conclude, “Collectively, these findings provide insights into potential diagnostic and therapeutic strategies aimed at evaluating and restoring gut microbial neurotransmitter homeostasis.”

Citations

“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, and Ningning Li, Cell Reports Medicine, January 13, 2025 (free online). Address: Ningning Li, Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518107, China, [email protected].