马乳酒样乳杆菌1207对CUMS小鼠焦虑及抑郁样行为的缓解作用

Lactobacillus kefiranofaciens 1207 alleviates anxiety and depression-like behavior in CUMS mice

摘要:

【目的】越来越多的研究表明，益生菌能够通过“微生物-肠-脑”轴来调节中枢神经系统，影响精神障碍疾病的发生和发展。因此，精神健康相关的益生菌资源的开发具有重要的意义。本文利用慢性不可预知温和应激小鼠模型(chronic unpredictable mild stress，CUMS)，研究了一株分离自西藏Kefir粒的马乳酒样乳杆菌1207对小鼠焦虑样和抑郁样行为的缓解作用。【方法】本研究构建了CUMS模型，并利用马乳酒样乳杆菌1207(10⁹ CFU/d)灌胃进行2周的干预。随后，分别利用旷场实验、悬尾实验和强迫游泳评估了该菌株对小鼠的焦虑样和抑郁样行为的影响；通过测定下丘脑、血清和脾脏中生物标记物的含量变化，研究了该菌株对色氨酸代谢、下丘脑-垂体-肾上腺(hypothalamic-pituitary-adrena，HPA)轴和炎症因子的调节作用。【结果】与对照小鼠相比，灌胃马乳酒样乳杆菌1207可显著增加小鼠在旷场实验中中央区域的滞留时间(P<0.05)；降低小鼠在悬尾实验(P<0.01)和强迫游泳实验(P<0.05)中的不动时间；可通过降低小鼠下丘脑中5-羟基吲哚乙酸/5-羟色胺来改善小鼠下丘脑的色氨酸代谢；通过降低血清中皮质酮(corticost erone,CORT)的水平，调控HPA轴的平衡；通过增加小鼠脾脏中抗炎细胞因子(inflammatory cytokines-10,IL-10)的相对表达量(P<0.05)，有效抑制炎症的发生。【结论】本研究表明，为期2周的马乳酒样乳杆菌1207灌胃干预可以有效调节“肠脑轴”相关生物标记物，显著改善小鼠焦虑样和抑郁样行为。本研究有助于为精神疾病的预防和治疗提供新的益生菌干预策略。

关键词:马乳酒样乳杆菌;肠-脑轴;焦虑样行为;抑郁样行为;生物标记物

Abstract:

[Objective] Increasing studies have proved that probiotics can regulate the central nervous system through the microbiome-gut-brain axis and affect the occurrence and development of mental disorders. Therefore, the development of probiotics resources related to mental health is of great significance. We employed the mouse model of chronic unpredictable mild stress (CUMS) to study the alleviating effects of Lactobacillus kefiranofaciens 1207 isolated from Tibet Kefir grains on the anxiety and depression behavior in mice. [Methods] The CUMS model was constructed and intragastrically administrated with L. kefiranofaciens 1207 (10⁹ CFU/d) for two weeks. The effects of the strain on the anxiety-like and depression-like behaviors of mice were evaluated by open field test, tail suspension test, and forced swimming test. The regulatory effects of the strain on tryptophan metabolism, hypothalamus-pituitary-adrenal axis, and inflammatory cytokines were evaluated based on the content of biomarkers in hypothalamus, serum, and spleen. [Results] Compared with the control, L. kefiranofaciens 1207 prolonged the retention time in the central region in the open field test (P<0.05), as well as the stationary time in the tail suspension test (P<0.01) and forced swimming test (P<0.05). Additionally, it improved the tryptophan metabolism of hypothalamus by reducing 5-hydroxyindoleacetic acid/5-hydroxytryptamine in mice and regulated the balance of hypothalamus- pituitary-adrenal axis by lowering the serum level of corticosterone. By up-regulating the relative expression of anti-inflammatory cytokine (inflammatory cytokines-10, IL-10) in mouse spleen (P<0.05), L. kefiranofaciens 1207 inhibited the occurrence of inflammation. [Conclusion] Two weeks of oral administration of L. kefiranofaciens 1207 can effectively regulate the biomarkers related to the gut-brain axis and alleviate the anxiety and depression-like behavior of mice. Our study provides new probiotic intervention strategies for the prevention and treatment of psychiatric disorders.

Key words:Lactobacillus kefiranofaciens;gut-brain axis;anxiety-like behavior;depression-like behavior;biomarker