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抗生素暴露可减轻慢性不可预测轻度应激诱导的焦虑样和抑郁样行为。

Antibiotics exposure attenuates chronic unpredictable mild stress-induced anxiety-like and depression-like behavior.

机构信息

Institute of Environmental Biology and Life Support Technology, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.

Institute of Environmental Biology and Life Support Technology, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China; State Key Laboratory of Software Development Environment, Beihang University, Beijing 100083, China.

出版信息

Psychoneuroendocrinology. 2022 Feb;136:105620. doi: 10.1016/j.psyneuen.2021.105620. Epub 2021 Dec 3.

DOI:10.1016/j.psyneuen.2021.105620
PMID:34896741
Abstract

Antibiotics exposure leads to gut microbiota dysbiosis, which increases the risk of anxiety and depression. However, the impact of ciprofloxacin and metronidazole exposure on chronic unpredictable mild stress-induced anxiety-like and depression-like behavior and underlying regulatory mechanism have not been well established. Here, chronic unpredictable mild stress model was established in adult male Sprague-Dawley rats. 16 S rRNA gene sequencing was used to decipher the gut microbiota. Enzyme-linked immunosorbent assay (ELIZA) was used to measure circulating cytokines in blood, gut barrier permeability biomarkers in feces, blood-brain barrier permeability biomarkers in brain. We found that antibiotics exposure significantly reduced the body weight, weight gain and liver health in chronic unpredictable mild stress treated rats. Behavioral testing suggested that antibiotics exposure reduced anxiety-like and depression-like behavior of rat. Antibiotics exposure possessed lower bacterial richness and diversity than that in the chronic unpredictable mild stress treated group. Compared with CUMS or CUMS-e group, higher abundances of Bacteroides, Lactobacillus, Lachnospiraceae and Akkermansia, lower abundances of S24-7, Blautia, Ruminocaceae, Ruminococcus and Prevotella were found in the gut microbiota from antibiotics exposure group. In addition, short-term antibiotics exposure increased the level of 5-hydroxytryptamine (5-HT) in brain. A significant correlation between certain bacteria and behavior of rats was observed, such as Roseburia. Our study uncovers the role for antibiotics in regulating chronic unpredictable mild stress-induced anxiety-like and depression-like behavior and suggest that short-term antibiotics exposure may be could reverse chronic unpredictable mild stress-induced anxiety-like and depression-like behavior.

摘要

抗生素暴露会导致肠道微生物群落失调,从而增加焦虑和抑郁的风险。然而,环丙沙星和甲硝唑暴露对慢性不可预测轻度应激诱导的焦虑样和抑郁样行为的影响及其潜在的调节机制尚未得到很好的确定。在这里,我们建立了成年雄性 Sprague-Dawley 大鼠慢性不可预测轻度应激模型。16S rRNA 基因测序用于破译肠道微生物群。酶联免疫吸附测定(ELISA)用于测量血液中的循环细胞因子、粪便中的肠道屏障通透性生物标志物、大脑中的血脑屏障通透性生物标志物。我们发现抗生素暴露显著降低了慢性不可预测轻度应激处理大鼠的体重、体重增加和肝脏健康。行为测试表明抗生素暴露降低了大鼠的焦虑样和抑郁样行为。抗生素暴露的细菌丰富度和多样性低于慢性不可预测轻度应激处理组。与 CUMS 或 CUMS-e 组相比,抗生素暴露组的肠道微生物群中拟杆菌、乳杆菌、lachnospiraceae 和 Akkermansia 的丰度更高,S24-7、Blautia、Ruminocaceae、Ruminococcus 和 Prevotella 的丰度更低。此外,短期抗生素暴露会增加大脑中 5-羟色胺(5-HT)的水平。观察到某些细菌与大鼠行为之间存在显著相关性,例如罗斯伯里氏菌。我们的研究揭示了抗生素在调节慢性不可预测轻度应激诱导的焦虑样和抑郁样行为中的作用,并表明短期抗生素暴露可能逆转慢性不可预测轻度应激诱导的焦虑样和抑郁样行为。

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