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Long-Term Exposure to Ceftriaxone Sodium Induces Alteration of Gut Microbiota Accompanied by Abnormal Behaviors in Mice.
Frontiers in Cellular and Infection Microbiology ( IF 4.6 ) Pub Date : 2020-05-04 , DOI: 10.3389/fcimb.2020.00258
Zhongyi Zhao 1 , Baoning Wang 2 , Liyuan Mu 3 , Hongren Wang 2 , Jingjing Luo 3 , Yuan Yang 2 , Hui Yang 2 , Mingyuan Li 2, 4 , Linlin Zhou 2 , Chuanmin Tao 1
Affiliation  

Background: Growing evidence points out that a disturbance of gut microbiota may also disturb the gut–brain communication. However, it is not clear to what extent the alteration of microbiota composition can modulate brain function, affecting host behaviors. Here, we investigated the effects of gut microbiota depletion on emotional behaviors.

Methods: Mice in the experimental group were orally administered ceftriaxone sodium solution (250 mg/ml, 0.2 ml/d) for 11 weeks. The open-field test and tail-suspension test were employed for the neurobehavioral assessment of the mice. Fecal samples were collected for 16s rDNA sequencing. The serum levels of cytokines and corticosterone were quantified using enzyme-linked immunosorbent assays. The immunohistochemistry method was used for the detection of brain-derived neurotrophic factor (BDNF) and c-Fos protein.

Results: The gut microbiota for antibiotic-treated mice showed lower richness and diversity compared with normal controls. This effect was accompanied by increased anxiety-like, depression-like, and aggressive behaviors. We found these changes to be possibly associated with a dysregulation of the immune system, abnormal activity of the hypothalamic-pituitary-adrenal axis, and an alteration of neurochemistry.

Conclusions: The findings demonstrate the indispensable role of microbiota in the gut–brain communication and suggest that the absence of conventional gut microbiota could affect the nervous system, influencing brain function.



中文翻译:

长期暴露于头孢曲松钠可导致小鼠肠道菌群改变,并伴有异常行为。

背景:越来越多的证据指出,肠道菌群的紊乱也可能会扰乱肠脑沟通。但是,尚不清楚微生物菌群组成的改变在多大程度上可调节脑功能,从而影响宿主行为。在这里,我们调查了肠道菌群耗竭对情绪行为的影响。

方法:实验组给小鼠口服头孢曲松钠溶液(250 mg / ml,0.2 ml / d),持续11周。采用开放视野试验和尾部悬垂试验对小鼠进行神经行为评估。收集粪便样本进行16s rDNA测序。使用酶联免疫吸附法对血清中的细胞因子和皮质酮水平进行定量。免疫组化方法用于检测脑源性神经营养因子(BDNF)和c-Fos蛋白。

结果:与正常对照相比,抗生素治疗小鼠的肠道菌群显示出较低的丰富度和多样性。这种效果伴随着焦虑症,抑郁症和攻击行为的增加。我们发现这些变化可能与免疫系统失调,下丘脑-垂体-肾上腺轴的异常活动以及神经化学改变有关。

结论: 这些发现证明了微生物群在肠脑交流中不可或缺的作用,并表明缺乏常规的肠道菌群会影响神经系统,影响大脑功能。

更新日期:2020-06-24
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