Over the past decade there has been increasing interest in the involvement of the microbiota-gut-brain axis in mental health. However, there are major gaps in our knowledge regarding the complex signaling systems through which gut microbes modulate the CNS. The immune system is a recognized mediator in the bidirectional communication continuously occurring between gut and brain. We previously demonstrated that Lactobacillus rhamnosus JB-1 (JB-1), a bacterial strain that has anxiolytic- and antidepressant-like effects in mice, modulates the immune system through induction of immunosuppressive T regulatory cells. Here we examined a potential causal relationship between JB-1 induced regulatory T cells and the observed effects on behaviour. We found that depletion of regulatory T cells, via treatment with monoclonal antibody against CD25, inhibited the antidepressant- and anxiolytic-like effects induced by 4-week oral administration of JB-1 in mice. Ly6Chi monocytes were found to be decreased in JB-1 fed mice with intact regulatory T cells, but not in JB-1 fed mice following depletion. Furthermore, adoptive transfer of CD4+CD25+ cells, from JB-1 treated donor mice, but not from controls, induced antidepressant- and anxiolytic-like effects in recipient mice. Ly6Chi monocytes were also significantly decreased in mice receiving CD4+CD25+ cells from JB1 fed donors. This study identifies cells within the CD4+CD25+ population, most likely regulatory T cells, as both necessary and sufficient in JB-1-induced antidepressant- and anxiolytic-like effects in mice, providing novel mechanistic insight into microbiota-gut-brain communication in addition to highlighting the potential for immunotherapy in psychiatric disorders.

中文翻译：

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CD4+CD25+ T 细胞对于鼠李糖乳杆菌 JB-1 在雄性 BALB/c 小鼠中的行为影响至关重要

在过去的十年中，人们对微生物群-肠-脑轴在心理健康中的作用越来越感兴趣。然而，我们对肠道微生物调节中枢神经系统的复杂信号系统的认识存在重大差距。免疫系统是肠道和大脑之间持续发生的双向通信中公认的中介。我们之前已经证明，鼠李糖乳杆菌 JB-1 (JB-1) 是一种在小鼠中具有抗焦虑和抗抑郁样作用的菌株，它通过诱导免疫抑制性 T 调节细胞来调节免疫系统。在这里，我们检查了 JB-1 诱导的调节性 T 细胞与观察到的对行为的影响之间的潜在因果关系。我们发现，通过用抗 CD25 的单克隆抗体处理，调节性 T 细胞的耗竭，抑制小鼠口服 JB-1 4 周诱导的抗抑郁和抗焦虑样作用。发现在具有完整调节性 T 细胞的 JB-1 喂养小鼠中，Ly6Chi 单核细胞减少，但在消耗后的 JB-1 喂养小鼠中没有。此外，来自 JB-1 治疗的供体小鼠而非对照的 CD4+CD25+ 细胞的过继转移在受体小鼠中诱导了抗抑郁和抗焦虑样作用。在接受来自 JB1 供体的 CD4+CD25+ 细胞的小鼠中，Ly6Chi 单核细胞也显着减少。这项研究确定了 CD4+CD25+ 群体中的细胞，最有可能是调节性 T 细胞，它们在 JB-1 诱导的小鼠抗抑郁和抗焦虑样作用中既必要又充分，