BACKGROUND Inflammasomes have been found to interact with the gut microbiota, and this effect is associated with depression, but the mechanisms underlying this interaction have not been elucidated in detail. RESULTS The locomotor activity of NLRP3 KO mice was significantly greater than that of their WT littermates, while cohousing and transplantation of the NLRP3 KO gut microbiota avoid the effects of NLRP3 KO on the general locomotor activity at baseline. Meanwhile, transplantation of the NLRP3 KO microbiota alleviated the CUS-induced depressive-like behaviors. The compositions of the gut microbiota in NLRP3 KO mice and WT mice were significantly different in terms of the relative abundance of Firmicutes, Proteobacteria, and Bacteroidetes. Fecal microbiota transplantation (FMT) from NLRP3 KO mice significantly ameliorated the depressive-like behavior induced by chronic unpredictable stress (CUS) in recipient mice. Given the correlation between circular RNA HIPK2 (circHIPK2) and depression and the observation that the level of circHIPK2 expression was significantly increased in CUS-treated mice compared with that in the control group, further experiments were performed. FMT significantly ameliorated astrocyte dysfunction in recipient mice treated with CUS via inhibition of circHIPK2 expression. CONCLUSIONS Our study illustrates the involvement of the gut microbiota-circHIPK2-astrocyte axis in depression, providing translational evidence that transplantation of the gut microbiota from NLRP3 KO mice may serve as a novel therapeutic strategy for depression.

中文翻译：

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来自NLRP3缺陷小鼠的肠道菌群可通过circHIPK2调节星形胶质细胞功能障碍，从而改善抑郁样行为。

背景技术已经发现炎性体与肠道菌群相互作用，并且这种作用与抑郁症相关，但是尚未详细阐明这种相互作用的潜在机制。结果NLRP3 KO小鼠的运动能力显着高于其野生同窝小鼠，而NLRP3 KO肠道菌群的寄居和移植避免了NLRP3 KO对基线时一般运动能力的影响。同时，NLRP3 KO菌群的移植减轻了CUS诱导的抑郁样行为。就纤毛虫，变形杆菌和拟杆菌的相对丰度而言，NLRP3 KO小鼠和野生型小鼠的肠道菌群组成明显不同。NLRP3 KO小鼠的粪便菌群移植（FMT）显着改善了受体小鼠的慢性不可预测压力（CUS）诱导的抑郁样行为。考虑到环状RNA HIPK2（circHIPK2）与抑郁之间的相关性，并且观察到与对照组相比，CUS治疗的小鼠中circHIPK2表达水平显着增加，因此进行了进一步的实验。FMT通过抑制circHIPK2表达，显着改善了接受CUS治疗的受体小鼠的星形胶质细胞功能障碍。结论我们的研究表明肠道菌群-circHIPK2-星形胶质细胞轴参与了抑郁症的研究，提供了从NLRP3 KO小鼠移植肠道菌群可能作为抑郁症治疗新策略的翻译证据。