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Transplantation of fecal microbiota from patients with alcoholism induces anxiety/depression behaviors and decreases brain mGluR1/PKC ε levels in mouse.
Biofactors ( IF 5.0 ) Pub Date : 2019-09-13 , DOI: 10.1002/biof.1567
Wenbo Zhao 1 , Ying Hu 2 , Chuangang Li 3 , Ning Li 3 , Shaowei Zhu 1 , Xu Tan 1 , Meng Li 1 , Yue Zhang 1 , Zheng Xu 1 , Zhaoxi Ding 1 , Lingming Hu 4 , Zengxun Liu 4 , Jinhao Sun 1
Affiliation  

Recent studies have revealed that the gut microbiota participates in the psychiatric behavior changes in disorders associated with alcohol. But it still remains unknown whether alcoholism is involved in changes in gut microbiota and its underlying mechanism is also not clear. Here, we tested the gut microbiota of patients with alcoholism and conducted fecal microbiota transplantation (FMT) from patients with alcoholism to C57BL/6J mice whose gut microbiota had been sharply suppressed with antibiotics (ABX). Then we evaluated their alcohol preference degree, anxiety, and depression‐like behaviors and social interaction behaviors, together with molecular changes in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). Our data indicated that the gut microbiota of patients with alcoholism was drastically different from those of the healthy adults. The abundance of p_Firmicutes was significantly increased whereas p_Bacteroidetes was decreased. Compared to mice transplanted with fecal microbiota from healthy male adults, the mice accepting fecal microbiota from patients with alcoholism showed (a) anxiety‐like and depression‐like behaviors, (b) decreased social interaction behaviors, (c) spontaneous alcohol preference, and (d) decreased brain‐derived neurotrophic factor (BDNF), alpha 1 subunit of GABA type A receptor (α1GABAAR) in mPFC and decreased metabotropic glutamate receptors 1 (mGluR1), protein kinase C (PKC) ε in NAc. Overall, our results suggest that fecal microbiota from patients with alcoholism did induce a status like alcohol dependence in C57BL/6J mice. The decreased expression of BDNF, α1GABAAR, and mGluR1/ PKC ε may be the underlying mechanism.

中文翻译:

酒精中毒患者的粪便微生物群移植会引起焦虑/抑郁行为,并降低小鼠的大脑mGluR1 / PKCε水平。

最近的研究表明,肠道菌群参与了酒精相关疾病的精神行为变化。但是,尚不清楚酒精中毒是否与肠道微生物群的变化有关,其潜在机制也不清楚。在这里,我们测试了酒精中毒患者的肠道菌群,并对酒精中毒患者的粪便微生物菌群移植(FMT)进行了肠道菌群被抗生素(ABX)显着抑制的C57BL / 6J小鼠的实验。然后我们评估了他们的酒精偏好程度,焦虑和抑郁样行为以及社交互动行为,以及前额内侧皮层(mPFC)和伏隔核(NAc)的分子变化。我们的数据表明,酒精中毒患者的肠道菌群与健康成年人的肠道菌群完全不同。丰富的p_Firmicutes显着增加,而p_Bacteroidetes减少。与从健康的成年男性中移植粪便菌群的小鼠相比,接受酒精中毒患者粪便菌群的小鼠表现出(a)焦虑和抑郁样行为,(b)社交互动行为减少,(c)自发性饮酒偏好,以及(d)降低脑源性神经营养因子(BDNF),α1个亚单位的GABA A型受体(α1GABA的中的mPFC R)和降低的代谢型谷氨酸受体1(mGluR1),蛋白激酶C(PKC)在εNAC。总体而言,我们的结果表明,酒精中毒患者的粪便菌群确实在C57BL / 6J小鼠中诱发了酒精依赖状态。BDNF,α1GABAA表达下降R和mGluR1 / PKCε可能是潜在的机制。
更新日期:2019-09-13
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