Journal of Zhejiang University

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

IL-1β pathway-dependent regulation of glutamate receptor activity by gut microbiota in bipolar depression

Author(s): Anying TANG, Yi CHEN, Kaijing DING, Jinyu ZHANG, Le XU, Wenhao CHEN, Shaohua HU, Jianbo LAI
Affiliation(s): Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; more
Corresponding email(s): dorhushaohua@zju.edu.cn, laijianbo@zju.edu.cn
Key Words: Bipolar disorder; Gut microbiota; Neuroinflammation; Glutamate receptors; Interleukin 1

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Anying TANG, Yi CHEN, Kaijing DING, Jinyu ZHANG, Le XU, Wenhao CHEN, Shaohua HU, Jianbo LAI. IL-1β pathway-dependent regulation of glutamate receptor activity by gut microbiota in bipolar depression[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2500219

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author="Anying TANG, Yi CHEN, Kaijing DING, Jinyu ZHANG, Le XU, Wenhao CHEN, Shaohua HU, Jianbo LAI",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2500219"
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%T IL-1β pathway-dependent regulation of glutamate receptor activity by gut microbiota in bipolar depression
%A Anying TANG
%A Yi CHEN
%A Kaijing DING
%A Jinyu ZHANG
%A Le XU
%A Wenhao CHEN
%A Shaohua HU
%A Jianbo LAI
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doi="https://doi.org/10.1631/jzus.B2500219"

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T1 - IL-1β pathway-dependent regulation of glutamate receptor activity by gut microbiota in bipolar depression
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A1 - Yi CHEN
A1 - Kaijing DING
A1 - Jinyu ZHANG
A1 - Le XU
A1 - Wenhao CHEN
A1 - Shaohua HU
A1 - Jianbo LAI
J0 - Journal of Zhejiang University Science B
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Y1 - in press
PB - Zhejiang University Press & Springer
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doi="https://doi.org/10.1631/jzus.B2500219"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: Objective: Neuroinflammation may disrupt neurotransmitter signaling. This study investigated whether gut microbiota-induced neuroinflammation can regulate glutamate pathways in bipolar disorder (BD). Methods: Fecal microbiota transplantation was performed to observe behavioral changes in the antibiotic-treated C57 BL/6J male mouse model of bipolar depression. Gut microbial structure, circulating and prefrontal levels of inflammatory factors, microglial activation, and transcription levels of N-methyl-D-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4 isoxazole receptor (AMPAR) genes were measured in the BD and control mice. Furthermore, the effects of IL-1 receptor antagonist on the glutamate pathways was assessed. Results: Compared with the control mice, BD mice displayed depression-like behaviors, with a lower diversity of gut bacteria and a decreased abundance of certain species. In addition, BD mice showed increased levels of inflammatory factors (e.g., IL-1β) in the serum and prefrontal cortex, microglial activation, and changes in the mRNA levels of NMDAR and AMPAR. Treatment with IL-1 receptor antagonist partially reversed the behavioral patterns, neuroinflammation, and transcription levels of glutamate receptors. Conclusion: The findings suggest that gut microbiota may influence glutamate receptor gene expression via an IL-1β-dependent pathway in a mouse model of BD, potentially contributing to neuroinflammatory mechanisms relevant to this disorder.

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On-line Access: 2025-09-05

Received: 2025-05-07

Revision Accepted: 2025-08-25

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Citations: Bibtex RefMan EndNote GB/T7714

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