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

14/08/2026

AI Summary

Gut microbiota alterations from FMT induced depression-like behaviour, reduced bacterial diversity, and decreased abundance of specific species in antibiotic-treated mice.
BD mice exhibited increased IL-1β and other inflammatory factors, microglial activation, and altered prefrontal and serum neuroinflammatory profiles.
IL-1 receptor antagonist partially reversed depressive behaviour, neuroinflammation, and NMDAR and AMPAR gene transcription changes, implicating an IL-1β-dependent pathway.

AI Summary

This study investigated whether gut microbiota-induced neuroinflammation can regulate glutamate pathways in bipolar disorder (BD).

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.

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.

Basic summary

J Zhejiang Univ Sci B. 2026 Jul 1;27(8):888-905. doi: 10.1631/jzus.B2500219.

ABSTRACT

OBJECTIVES: 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 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 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.

PMID:42599179 | DOI:10.1631/jzus.B2500219

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