Probiotic Lactobacillus casei strain Shirota relieves stress-associated symptoms by modulating the gut-brain interaction in human and animal models

Probiotic Lactobacillus casei strain Shirota relieves stress-associated symptoms by modulating the gut-brain interaction in human and animal models
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DOI:
10.1111/nmo.12804
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发表时间:
2016-07-01
影响因子:
3.5
通讯作者:
Rokutan, K.
Rokutan, K.
中科院分区:
医学3区
文献类型:
--
作者:
Takada, M.;Nishida, K.;Rokutan, K.

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本研究旨在研究干酪乳杆菌菌株Shirota(LcS)对应激条件下肠-脑相互作用的影响。方法采用3个双盲、安慰剂对照试验,观察LcS对健康医学生学业考试应激状态下心理和生理应激反应的影响。受试者在参加国家标准化考试之前每天接受LcS发酵乳或安慰剂治疗8周。主观焦虑评分,唾液皮质醇水平,并在干预期间的身体症状的存在进行汇总和分析。在动物研究中,大鼠给予含或不含LcS的饲料2周,然后进行避水应激(WAS)。WAS后即刻测定血浆皮质酮浓度、室旁核(PVN)cFos和促肾上腺皮质激素释放因子(CRF)的表达。在一项电生理研究中,胃迷走神经传入神经活动进行了监测后,灌胃给药的LcS麻醉大鼠。关键结果:与安慰剂组相比,LcS组的学习压力引起的唾液皮质醇水平升高和身体症状发生率显著降低。在用LcS预处理的大鼠中,WAS诱导的血浆皮质酮增加被显著抑制,并且PVN中CRF表达细胞的数量减少。灌胃给予LcS以剂量依赖性方式刺激胃迷走神经传入活动。结论与推论这些研究结果表明,LCS可能会防止皮质醇分泌过多和身体症状的压力条件下,可能通过迷走神经传入信号的大脑和减少压力反应的PVN。
Background This study aimed to examine the effects of Lactobacillus casei strain Shirota (LcS) on gut-brain interactions under stressful conditions. Methods Three double-blind, placebo-controlled trials were conducted to examine the effects of LcS on psychological and physiological stress responses in healthy medical students under academic examination stress. Subjects received LcS-fermented milk or placebo daily for 8 weeks prior to taking a national standardized examination. Subjective anxiety scores, salivary cortisol levels, and the presence of physical symptoms during the intervention were pooled and analyzed. In the animal study, rats were given feed with or without LcS for 2 weeks, then submitted to water avoidance stress (WAS). Plasma corticosterone concentration and the expression of cFos and corticotropin releasing factor (CRF) in the paraventricular nucleus (PVN) were measured immediately after WAS. In an electrophysiological study, gastric vagal afferent nerve activity was monitored after intragastric administration of LcS to urethane-anesthetized rats. Key Results Academic stress-induced increases in salivary cortisol levels and the incidence rate of physical symptoms were significantly suppressed in the LcS group compared with the placebo group. In rats pretreated with LcS, WAS-induced increases in plasma corticosterone were significantly suppressed, and the number of CRF-expressing cells in the PVN was reduced. Intragastric administration of LcS stimulated gastric vagal afferent activity in a dose-dependent manner. Conclusions & Inferences These findings suggest that LcS may prevent hypersecretion of cortisol and physical symptoms under stressful conditions, possibly through vagal afferent signaling to the brain and reduced stress reactivity in the PVN.