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肠道益生菌效应可预防慢性心理应激诱导的小鼠大脑活动异常。

Probiotic gut effect prevents the chronic psychological stress-induced brain activity abnormality in mice.

作者信息

Ait-Belgnaoui A, Colom A, Braniste V, Ramalho L, Marrot A, Cartier C, Houdeau E, Theodorou V, Tompkins T

机构信息

Neuro-Gastroenterologie et Nutrition team, TOXALIM, UMR 1331-INRA/INP/UPS, Toulouse, France; Lallemand Health Solutions Inc., Montreal, QC, Canada.

出版信息

Neurogastroenterol Motil. 2014 Apr;26(4):510-20. doi: 10.1111/nmo.12295. Epub 2013 Dec 30.

Abstract

BACKGROUND

A probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 combination, Probio'Stick(®) ) displays anxiolytic-like activity and reduces apoptosis in the lymbic system in animal models of depression. Based on the hypothesis that modulation of gut microbiota by this probiotic formulation has beneficial effects on brain activity in stress conditions, we report a set of probiotic-evoked physiological, cellular, and molecular events in the brain of Probio'Stick(®) pretreated mice submitted to chronic psychological stress.

METHODS

Water avoidance stress (WAS) was applied or not (sham). Hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) responses to the chronic stress were assessed through plasma corticosterone and catecholamine measurements. Specific markers for neuronal activity, neurogenesis, and synaptic plasticity were used to assess brain activity. In addition, gut permeability and tight junction (TJ) proteins levels were also determinated.

KEY RESULTS

We observed that a pretreatment with the probiotic formulation attenuated HPA axis and ANS activities in response to WAS, and reduced cFos expression in different brain areas but Lactobacillus salivarius (a negative control) treatment was ineffective on these parameters. Moreover, probiotic pretreatment prevented the WAS-induced decrease hippocampal neurogenesis and expression changes in hypothalamic genes involved in synaptic plasticity. These central effects were associated with restoration of TJ barrier integrity in stressed mice.

CONCLUSIONS & INFERENCES: These data suggest that chronic stress-induced abnormal brain plasticity and reduction in neurogenesis can be prevented by a pretreatment with the Probio'Stick(®) formulation, suggesting that probiotics modulate neuroregulatory factors and various signaling pathways in the central nervous system involved in stress response.

摘要

背景

一种益生菌制剂(瑞士乳杆菌R0052和长双歧杆菌R0175组合,Probio'Stick®)在抑郁症动物模型中表现出抗焦虑样活性,并减少边缘系统中的细胞凋亡。基于这种益生菌制剂对肠道微生物群的调节在应激条件下对大脑活动有有益影响的假设,我们报告了一组在经受慢性心理应激的Probio'Stick®预处理小鼠大脑中由益生菌引发的生理、细胞和分子事件。

方法

施加或不施加水回避应激(WAS)(假手术)。通过测量血浆皮质酮和儿茶酚胺来评估下丘脑-垂体-肾上腺(HPA)轴和自主神经系统(ANS)对慢性应激的反应。使用神经元活动、神经发生和突触可塑性的特定标志物来评估大脑活动。此外,还测定了肠道通透性和紧密连接(TJ)蛋白水平。

关键结果

我们观察到,用益生菌制剂预处理可减弱对WAS的HPA轴和ANS活动,并降低不同脑区的cFos表达,但唾液乳杆菌(阴性对照)处理对这些参数无效。此外,益生菌预处理可防止WAS诱导的海马神经发生减少以及下丘脑参与突触可塑性的基因表达变化。这些中枢效应与应激小鼠TJ屏障完整性的恢复有关。

结论与推论

这些数据表明,用Probio'Stick®制剂预处理可预防慢性应激诱导的异常脑可塑性和神经发生减少,这表明益生菌可调节中枢神经系统中参与应激反应的神经调节因子和各种信号通路。

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