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

Author

Listed:
  • You Yu

    (Chinese Academy of Sciences)

  • Bing Zhang

    (Chinese Academy of Sciences
    University of 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
    University of Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

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.

Suggested Citation

  • You Yu & Bing Zhang & Peifeng Ji & Zhenqiang Zuo & Yongxi Huang & Ning Wang & Chang Liu & Shuang-Jiang Liu & Fangqing Zhao, 2022. "Changes to gut amino acid transporters and microbiome associated with increased E/I ratio in Chd8+/− mouse model of ASD-like behavior," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28746-2
    DOI: 10.1038/s41467-022-28746-2
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    1. Joseph T. Glessner & Kai Wang & Guiqing Cai & Olena Korvatska & Cecilia E. Kim & Shawn Wood & Haitao Zhang & Annette Estes & Camille W. Brune & Jonathan P. Bradfield & Marcin Imielinski & Edward C. Fr, 2009. "Autism genome-wide copy number variation reveals ubiquitin and neuronal genes," Nature, Nature, vol. 459(7246), pages 569-573, May.
    2. Hanna Hörnberg & Enrique Pérez-Garci & Dietmar Schreiner & Laetitia Hatstatt-Burklé & Fulvio Magara & Stephane Baudouin & Alex Matter & Kassoum Nacro & Eline Pecho-Vrieseling & Peter Scheiffele, 2020. "Rescue of oxytocin response and social behaviour in a mouse model of autism," Nature, Nature, vol. 584(7820), pages 252-256, August.
    3. Yuta Katayama & Masaaki Nishiyama & Hirotaka Shoji & Yasuyuki Ohkawa & Atsuki Kawamura & Tetsuya Sato & Mikita Suyama & Toru Takumi & Tsuyoshi Miyakawa & Keiichi I. Nakayama, 2016. "CHD8 haploinsufficiency results in autistic-like phenotypes in mice," Nature, Nature, vol. 537(7622), pages 675-679, September.
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    Cited by:

    1. Cheng Peng & Yuanna Cheng & Mingtong Ma & Qiu Chen & Yongjia Duan & Shanshan Liu & Hongyu Cheng & Hua Yang & Jingping Huang & Wenyi Bu & Chenyue Shi & Xiangyang Wu & Jianxia Chen & Ruijuan Zheng & Zho, 2024. "Mycobacterium tuberculosis suppresses host antimicrobial peptides by dehydrogenating L-alanine," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. D. Garrett Brown & Michaela Murphy & Roberto Cadeddu & Rickesha Bell & Allison Weis & Tyson Chiaro & Kendra Klag & Jubel Morgan & Hilary Coon & W. Zac Stephens & Marco Bortolato & June L. Round, 2024. "Colitis reduces active social engagement in mice and is ameliorated by supplementation with human microbiota members," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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