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肠道微生物群与心理应激诱导的肠道和血脑屏障缺陷有关。

Gut Microbiota Are Associated With Psychological Stress-Induced Defections in Intestinal and Blood-Brain Barriers.

作者信息

Geng Shaohui, Yang Liping, Cheng Feng, Zhang Zhumou, Li Jiangbo, Liu Wenbo, Li Yujie, Chen Yukun, Bao Yu, Chen Lin, Fei Zihao, Li Xinmin, Hou Junlin, Lin Yuan, Liu Zhilin, Zhang Shuai, Wang Hengtao, Zhang Qing, Wang Honggang, Wang Xiaodan, Zhang Jingtao

机构信息

First Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, China.

Basic Medical College, Henan University of Chinese Medicine, Zhengzhou, China.

出版信息

Front Microbiol. 2020 Jan 15;10:3067. doi: 10.3389/fmicb.2019.03067. eCollection 2019.

Abstract

Altered gut microbiota has been identified during psychological stress, which causes severe health issues worldwide. The integrity of the intestinal barrier and blood-brain barrier regulates the process of bacterial translocation and can supply the nervous system with real-time information about the environment. However, the association of gut microbiota with psychological stress remains to be fully interpreted. In this study, we established a psychological stress model using an improved communication box and compared the expression of tight junction proteins in multiple regions of the intestinal (duodenum, jejunum, ileum) and blood-brain (amygdala, hippocampus) barriers between model and control rats. We also conducted fecal microbiota analysis using 16S rRNA gene sequencing. Expression levels of the stress-related indicators adrenocorticotropic hormone, NR3C1,2, and norepinephrine were increased in the model group compared to control group. Psychological stress reduced brain and intestinal levels of tight junction proteins, including claudin5, occludin, α-actin, and ZO-1. Microbiota analysis revealed elevated microbial diversity and fecal proportions of , , and in the model group. Further analysis indicated a negative correlation of and , as well as a positive correlation of , , and , with claudin5, occludin, α-actin, and ZO-1. Our use of a rodent model to explore the association between compromised intestinal and blood-brain barriers and altered fecal microbiota under psychological stress improves our understanding of the gut-brain axis. Here, cues converge to control basic developmental processes in the intestine and brain such as barrier function. This study provides new directions for investigating the pathogenesis of emotional disorders and the formulation of clinical treatment.

摘要

在心理应激过程中已发现肠道微生物群发生改变,这在全球范围内导致了严重的健康问题。肠道屏障和血脑屏障的完整性调节细菌易位过程,并能为神经系统提供有关环境的实时信息。然而,肠道微生物群与心理应激之间的关联仍有待充分阐释。在本研究中,我们使用改良的通讯箱建立了心理应激模型,并比较了模型大鼠和对照大鼠肠道(十二指肠、空肠、回肠)和血脑(杏仁核、海马体)屏障多个区域紧密连接蛋白的表达。我们还使用16S rRNA基因测序进行了粪便微生物群分析。与对照组相比,模型组中应激相关指标促肾上腺皮质激素、NR3C1、2和去甲肾上腺素的表达水平升高。心理应激降低了大脑和肠道中紧密连接蛋白的水平,包括闭合蛋白5、闭合蛋白、α-肌动蛋白和紧密连接蛋白1。微生物群分析显示模型组中微生物多样性增加,以及 、 和 的粪便比例升高。进一步分析表明 与 呈负相关,以及 、 和 与闭合蛋白5、闭合蛋白、α-肌动蛋白和紧密连接蛋白1呈正相关。我们使用啮齿动物模型来探索心理应激下受损的肠道和血脑屏障与粪便微生物群改变之间的关联,这增进了我们对肠脑轴的理解。在这里,各种线索汇聚在一起,以控制肠道和大脑中的基本发育过程,如屏障功能。本研究为情感障碍的发病机制研究和临床治疗方案的制定提供了新的方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c950/6974438/ee4039bfd654/fmicb-10-03067-g001.jpg

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