Abstract: ObjectiveNeuroinflammation may disrupt neurotransmitter signaling. This study investigated whether gut microbiota-induced neuroinflammation can regulate glutamate pathways in bipolar disorder (BD).
MethodsFecal 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.
ResultsCompared 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.
ConclusionsThe 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.

双相抑郁肠道菌群可通过IL-1β通路调节谷氨酸受体活性

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