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Benef Microbes. 2022 Aug 3;13(3):253-264. doi: 10.3920/BM2021.0188. Epub 2022 Jul 4.
The microbiota-gut-brain axis is important in anxiety-depressive disorders. These conditions are associated with dysbiosis of the intestinal microbiota, intestinal hyperpermeability and an increase in circulating markers of inflammation and oxidative stress. They are also associated with a deregulation of the glutamine-glutamate-γ-aminobutyric acid cycle, with impairment of the excitatory/inhibitory balance in the brain. Our aim was to examine the impact of chronic treatment with the probiotic organism , alone or in combination with glutamine and curcumin, in a validated model of anxiety-depressive disorder in mice. Six-month-old mice (n=144) were exposed to chronic unpredictable mild stress (CUMS) stimulation for 3 weeks and emotional disturbances were assessed using two tests assessing anxiety (elevated plus maze test) and depressive-like behaviour (tail suspension test). After discontinuation of CUMS, mice were force-fed once-daily with curcumin, glutamine and probiotic alone or in combination for 21 consecutive days. Emotional reactivity was assessed in two separate behavioural tests: open field test and forced swim test. The outcomes of the interventions were compared with those induced by acute intraperitoneal administration of clomipramine, one of the major tricyclic antidepressants used in humans. Two independent sets of experiment were performed in this study, in order to evaluate the effects of two different formulations based on the utilisation of the probiotic in its live or inactivated form. CUMS led to an impairment of the emotional state of 6-month-old mice. However, chronic treatment with a combination of glutamine, curcumin and rescued the anxiety and depressive-like phenotype with an efficiency similar to clomipramine. A synergistic effect of the three compounds was observed, suggesting that simultaneous action on different targets is a relevant approach for the management of anxiety-depressive disorders.
肠道菌群-肠-脑轴在焦虑抑郁障碍中具有重要作用。这些疾病与肠道菌群失调、肠道通透性增加以及循环炎症和氧化应激标志物增加有关。它们还与谷氨酰胺-谷氨酸-γ-氨基丁酸循环的调节失常有关，导致大脑中的兴奋/抑制平衡受损。我们的目的是研究单独或联合使用益生菌、谷氨酰胺和姜黄素对经过验证的焦虑抑郁障碍小鼠模型的慢性治疗的影响。将 6 月龄的小鼠（n=144）暴露于慢性不可预测的轻度应激（CUMS）刺激 3 周，并用两种测试评估焦虑（高架十字迷宫测试）和抑郁样行为（悬尾测试）评估情绪障碍。停止 CUMS 后，小鼠连续 21 天每天口服给予姜黄素、谷氨酰胺和益生菌，单独或联合使用。在两个单独的行为测试中评估情绪反应：旷场测试和强迫游泳测试。将干预的结果与人类使用的主要三环抗抑郁药之一氯米帕明的急性腹腔内给药引起的结果进行比较。在这项研究中进行了两组独立的实验，以评估基于益生菌的两种不同制剂的效果，即使用其活的或灭活的形式。CUMS 导致 6 月龄小鼠的情绪状态受损。然而，谷氨酰胺、姜黄素和益生菌的联合慢性治疗挽救了焦虑和抑郁样表型，其效率与氯米帕明相似。三种化合物具有协同作用，表明同时作用于不同靶点是治疗焦虑抑郁障碍的一种相关方法。
