Department of Forensic Pathology, China Medical University School of Forensic Medicine, Shenyang, 110122, Liaoning, PR China.
Liaoning Province Key Laboratory of Forensic Bio-evidence Sciences, Shenyang, 110122, Liaoning, PR China.
Mol Psychiatry. 2023 Feb;28(2):919-930. doi: 10.1038/s41380-022-01841-y. Epub 2022 Oct 24.
Chronic ethanol exposure (CEE), which can lead to neuroinflammation, is an increasing risk factor for depression disorder, but the underlying mechanism is not clear. Recent observations have revealed the associations among psychiatric disorders, ethanol exposure and alterations of the gut microbiota. Here, we found that CEE induced depressive-like behavior, which could be alleviated by probiotics and transferred from donor to recipient mice by fecal microbiota transplantation (FMT). Neuroinflammation and the activation of the NLRP3 inflammasome were also observed in recipient mice. The downregulation of NLRP3 in the hippocampus mitigated CEE-induced depressive-like behavior and neuroinflammation but had no significant effect on FMT recipient mice. Moreover, elevated serum inflammatory factors in recipient mice showed a significant mediation effect between the gut microbiota and depressive-like behavior. Together, our study findings indicate that the gut microbiota contributes to both hippocampal NLRP3-mediated neuroinflammation and depressive-like behavior induced by CEE, which may open avenues for potential interventions against CEE-associated psychiatric disorders.
慢性乙醇暴露（CEE）可导致神经炎症，是抑郁症的一个日益增加的风险因素，但潜在机制尚不清楚。最近的观察结果揭示了精神疾病、乙醇暴露和肠道微生物组改变之间的关联。在这里，我们发现 CEE 诱导了抑郁样行为，益生菌可缓解这种行为，并且可通过粪便微生物群移植（FMT）从供体转移到受体小鼠。在受体小鼠中也观察到神经炎症和 NLRP3 炎性小体的激活。海马中 NLRP3 的下调减轻了 CEE 诱导的抑郁样行为和神经炎症，但对 FMT 受体小鼠没有显著影响。此外，受体小鼠中升高的血清炎症因子在肠道微生物群和抑郁样行为之间表现出显著的中介效应。总之，我们的研究结果表明，肠道微生物群有助于 CEE 诱导的海马 NLRP3 介导的神经炎症和抑郁样行为，这可能为针对 CEE 相关精神疾病的潜在干预措施开辟途径。
