Towards a psychobiotic therapy for depression: Bifidobacterium breve CCFM1025 reverses chronic stress-induced depressive symptoms and gut microbial abnormalities in mice
Towards a psychobiotic therapy for depression: Bifidobacterium breve CCFM1025 reverses chronic stress-induced depressive symptoms and gut microbial abnormalities in mice
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DOI：
10.1016/j.ynstr.2020.100216
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发表时间：
2020-05-01
影响因子：
5
通讯作者：
Chen, Wei
中科院分区：
文献类型：
--
作者：
Tian, Peijun;O'Riordan, Kenneth J.;Chen, Wei
背景：越来越多的证据表明肠道微生物异常与抑郁症之间存在关联。考虑到目前药理学方法的许多局限性，微生物-肠-脑轴是使用营养策略治疗抑郁症的新兴靶点。在这里，我们研究了精神生物治疗对depress.Methods的效果和可能的机制：慢性应激C57 BL/6 J雄性小鼠5周前的行为测试前给予活的短双歧杆菌CCFM 1025。脑神经系统的变化，血清皮质酮，细胞因子水平，粪便微生物组成，和短链脂肪酸（SCFA）含量进行了测量。此外，SCFA对5-羟色氨酸（5-HTP）的生物合成的影响进行了研究，在肠嗜铬细胞（RIN 14 B）的体外模型。过度活跃的下丘脑-垂体-肾上腺反应，以及炎症，也得到缓解，可能通过调节糖皮质激素受体（Nr 3c 1）的表达。此外，CCFM 1025还下调pCREB-c-Fos通路，但增加脑源性神经营养因子（BDNF）的表达。与此同时，慢性应激诱导的肠道微生物异常得到恢复，同时SCFA和5-HTP水平升高。肠道5-HTP生物合成与粪便SCFA和短双歧杆菌levels.Conclusions：总之，短双歧杆菌CCFM 1025显示出相当大的抗抑郁样和微生物群调节作用，这开辟了新的治疗策略，对治疗抑郁症的途径。
Background: Accumulating evidence points to an association between gut microbial abnormalities and depression disorder. The microbiota-gut-brain axis is an emerging target for treating depression using nutritional strategies, considering the numerous limitations of current pharmacological approaches. Here we studied the effect and probable mechanisms of psychobiotic treatment on depression.Methods: Chronically stressed C57BL/6J male mice were administered viable Bifidobacterium breve CCFM1025 for 5 weeks prior to behavioral testing. Brain neurological alterations, serum corticosterone, cytokines levels, fecal microbial composition, and short-chain fatty acid (SCFA) content were measured. In addition, the effect of SCFA on 5-hydroxytryptophan (5-HTP) biosynthesis was investigated in an in vitro model of enterochromaffin cells (RIN14B).Results: CCFM1025 treatment significantly reduced depression- and anxiety-like behaviors. The hyperactive hypothalamic-pituitary-adrenal response, as well as inflammation, were also alleviated, possibly via regulating the expression of glucocorticoid receptors (Nr3c1). Moreover, CCFM1025 also down-regulated the pCREB-c-Fos pathway but increased the expression of brain-derived neurotrophic factor (BDNF). Meanwhile, chronic stress-induced gut microbial abnormalities were restored, accompanied by increased SCFA and 5-HTP levels. The intestinal 5-HTP biosynthesis positively correlated with fecal SCFA and Bifidobacterium breve levels.Conclusions: In summary, Bifidobacterium breve CCFM1025 showed considerable antidepressant-like and microbiota-regulating effects, which opens avenues for novel therapeutic strategies towards treating depression.