Towards a psychobiotic therapy for depression: Bifidobacterium breve CCFM1025 reverses chronic stress-induced depressive symptoms and gut microbial abnormalities in mice,Neurobiology of Stress

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Towards a psychobiotic therapy for depression: Bifidobacterium breve CCFM1025 reverses chronic stress-induced depressive symptoms and gut microbial abnormalities in mice
Neurobiology of Stress ( IF 5 ) Pub Date : 2020-03-20 , DOI: 10.1016/j.ynstr.2020.100216
Peijun Tian _{1,

2} , Kenneth J O'Riordan _{3,

4} , Yuan-Kun Lee ₅ , Gang Wang _{1,

2,

6,

7} , Jianxin Zhao _{1,

2,

6} , Hao Zhang _{1,

2,

7,

8,

9} , John F Cryan _{3,

4} , Wei Chen _{1,

2,

8,

10}

Affiliation

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.
School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.
APC Microbiome Ireland, University College Cork, Cork, Ireland.
Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
Department of Microbiology & Immunology, National University of Singapore, Singapore, 117597, Singapore.
International Joint Research Center for Probiotics & Gut Health, Jiangnan University, Wuxi, Jiangsu, China.
Yangzhou Institute of Food Biotechnology, Jiangnan University, Yangzhou, Jiangsu, China.
National Engineering Center of Functional Food, Jiangnan University, Wuxi, Jiangsu, China.
Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute Wuxi Branch, Wuxi, 214122, PR China.
Beijing Innovation Centre of Food Nutrition and Human Health, Beijing Technology and Business University, Beijing, China.

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.

中文翻译：

抑郁症的精神生物疗法：短双歧杆菌 CCFM1025 可逆转小鼠慢性应激诱发的抑郁症状和肠道微生物异常

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。考虑到当前药理学方法的众多局限性，微生物群-肠-脑轴是使用营养策略治疗抑郁症的一个新兴目标。在这里，我们研究了精神药物治疗抑郁症的效果和可能的机制。

方法

在行为测试之前，对慢性应激的 C57BL/6J 雄性小鼠施用活的短双歧杆菌CCFM1025 5 周。测量了脑神经改变、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。此外，我们还在肠嗜铬细胞 (RIN14B)体外模型中研究了 SCFA 对 5-羟色氨酸 (5-HTP) 生物合成的影响。

结果

CCFM1025 治疗显着减少了抑郁和焦虑样行为。过度活跃的下丘脑-垂体-肾上腺反应以及炎症也得到缓解，这可能是通过调节糖皮质激素受体（Nr3c1）的表达来实现的。此外，CCFM1025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，慢性应激引起的肠道微生物异常得到恢复，同时 SCFA 和 5-HTP 水平增加。肠道 5-HTP 生物合成与粪便 SCFA 和短双歧杆菌水平呈正相关。