Changes to gut amino acid transporters and microbiome associated with increased E/I ratio in Chd8+/− mouse model of ASD-like behavior

You Yu, Bing Zhang, Peifeng Ji, Zhenqiang Zuo, Yongxi Huang, Ning Wang, Chang Liu, Shuang-Jiang Liu and Fangqing Zhao ()
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You Yu: Chinese Academy of Sciences
Bing Zhang: Chinese Academy of Sciences
Peifeng Ji: Chinese Academy of Sciences
Zhenqiang Zuo: Chinese Academy of Sciences
Yongxi Huang: Chinese Academy of Sciences
Ning Wang: Chinese Academy of Sciences
Chang Liu: Chinese Academy of Sciences
Shuang-Jiang Liu: Chinese Academy of Sciences
Fangqing Zhao: Chinese Academy of Sciences

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Autism spectrum disorder (ASD), a group of neurodevelopmental disorders characterized by social communication deficits and stereotyped behaviors, may be associated with changes to the gut microbiota. However, how gut commensal bacteria modulate brain function in ASD remains unclear. Here, we used chromodomain helicase DNA-binding protein 8 (CHD8) haploinsufficient mice as a model of ASD to elucidate the pathways through which the host and gut microbiota interact with each other. We found that increased levels of amino acid transporters in the intestines of the mouse model of ASD contribute to the high level of serum glutamine and the increased excitation/inhibition (E/I) ratio in the brain. In addition, elevated α-defensin levels in the haploinsufficient mice resulted in dysregulation of the gut microbiota characterized by a reduced abundance of Bacteroides. Furthermore, supplementation with Bacteroides uniformis improved the ASD-like behaviors and restored the E/I ratio in the brain by decreasing intestinal amino acid transport and the serum glutamine levels. Our study demonstrates associations between changes in the gut microbiota and amino acid transporters, and ASD-like behavioral and electrophysiology phenotypes, in a mouse model.

Date: 2022
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DOI: 10.1038/s41467-022-28746-2

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