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

Anying TANG; Yi CHEN; Kaijing DING; Jinyu ZHANG; Le XU; Wenhao CHEN; Shaohua HU; Jianbo LAI

doi:10.1631/jzus.B2500219

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Research Article | Updated：2026-08-13

IL-1β pathway-dependent regulation of glutamate receptor activity by gut microbiota in bipolar depression
IL-1β pathway-dependent regulation of glutamate receptor activity by gut microbiota in bipolar depression
双相抑郁肠道菌群可通过IL-1β通路调节谷氨酸受体活性
Journal of Zhejiang University-SCIENCE B Vol. 27, Issue 8, Pages: 888-905(2026)
Affiliations：

1.Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
2.Zhejiang Key Laboratory of Precision Psychiatry, Hangzhou 310003, China
3.Nanhu Brain-computer Interface Institute, Hangzhou 311100, China
4.Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou 311121, China
5.Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310013, China
6.Wenzhou Medical University, Wenzhou 325035, China
7.Brain Research Institute of Zhejiang University, Hangzhou 310058, China
8.Zhejiang Engineering Center for Mathematical Mental Health, Hangzhou 310003, China
9.The MOE Frontier Science Center for Brain Science and Brain-machine Integration, Zhejiang University School of Medicine, Hangzhou 310058, China
10.Department of Psychology and Behavioral Sciences, Zhejiang University, Hangzhou 310058, China
Funds：
DOI：10.1631/jzus.B2500219
CLC：
CSTR：
Received：07 May 2025，

Revised：2025-08-25，

Online First：13 August 2026，

Published：13 August 2026
Accepted：

汤安英,陈艺,丁凯景等.双相抑郁肠道菌群可通过IL-1β通路调节谷氨酸受体活性[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2026,27(08):888-905.

Anying TANG, Yi CHEN, Kaijing DING, et al. IL-1β pathway-dependent regulation of glutamate receptor activity by gut microbiota in bipolar depression[J]. Journal of Zhejiang University-SCIENCE B, 2026, 27(8): 888-905.
汤安英,陈艺,丁凯景等.双相抑郁肠道菌群可通过IL-1β通路调节谷氨酸受体活性[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2026,27(08):888-905. DOI： 10.1631/jzus.B2500219.

Anying TANG, Yi CHEN, Kaijing DING, et al. IL-1β pathway-dependent regulation of glutamate receptor activity by gut microbiota in bipolar depression[J]. Journal of Zhejiang University-SCIENCE B, 2026, 27(8): 888-905. DOI： 10.1631/jzus.B2500219.

摘要

神经炎症可能会干扰神经递质的信号传递。本研究旨在探究肠道菌群引发的神经炎症是否影响双相障碍患者脑内的谷氨酸通路。本研究通过对双相抑郁患者粪便移植，观察抗生素预处理的C57BL/6J雄性小鼠行为变化，并对双相抑郁移植组和对照组小鼠的肠道菌群结构、血清和前额叶炎症因子水平、前额叶小胶质细胞活化情况以及

-甲基-

-天冬氨酸受体（

NMDAR

）和α-氨基-3-羟基-5-甲基-4-异唑受体（

AMPAR

）基因转录水平进行了检测。此外，还评估了白细胞介素-1（IL-1）受体拮抗剂对小鼠行为以及谷氨酸通路的影响。结果显示，与对照小鼠相比，移植组小鼠表现出抑郁样行为，其肠道菌群的多样性更低。此外，移植组小鼠血清和前额叶中IL-1β水平升高，小胶质细胞活化增加，

NMDAR

和

AMPAR

的转录水平也有不同水平的变化，且经IL-1受体拮抗剂治疗后可得到部分改善。综上，在双相抑郁粪菌移植小鼠模型中，肠道菌群可能通过依赖于IL-1β通路影响谷氨酸受体的基因表达，这可能与该疾病的神经炎症机制相关。

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 (FMT) was performed to observe behavioral changes in the antibiotic-treated C57BL/6J male mouse model of bipolar depression. Gut microbial structure

circulating

and prefrontal levels of inflammatory factors

microglial activation

and transcription levels of

-methyl-

-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 interleukin-1 (IL-1) receptor antagonist (IL-1RA) on the glutamate pathways were 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 messenger RNA (mRNA) levels of

NMDAR

and

AMPAR

. Treatment with IL-1RA partially reversed the behavioral patterns

neuroinflammation

and transcription levels of glutamate receptors.

Conclusions

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.

关键词

Keywords

references

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