Nature子刊:肠道菌群失调诱发小鼠抑郁症的机制
创作:大月半 审核:szx 2020年12月17日
  • UCMS诱导小鼠的抑郁样行为,通过粪菌移植可将抑郁样行为传递给无菌小鼠,并减少海马神经发生;
  • 机制上,UCMS诱导的菌群失调(以乳杆菌科的减少为特征)改变了脂肪酸的代谢,降低了大麻素受体1(CB1)配体的前体浓度,从而抑制了内源性大麻素(eCB)信号介导的mTOR信号通路活化;
  • 阻断eCB降解酶、补充花生四烯酸(eCB的前体)或补充植物乳杆菌,均可恢复海马中的eCB水平及神经发生,并缓解菌群失调诱导的小鼠抑郁样行为。
主编推荐语
szx
Nature Communications上发表的一项最新研究,在慢性不可预测的轻度压力(UCMS)诱导的小鼠抑郁症模型中,发现UCMS可通过诱导肠道菌群失调,影响脂肪酸的代谢,以抑制内源性大麻素信号的激活,从而降低小鼠的海马神经发生,并引发抑郁样行为。恢复内源性大麻素信号,或补充特定菌株以调节肠道菌群,可缓解小鼠的抑郁样行为。该研究结果提示,饮食或益生菌干预或可作为改善抑郁症的潜在手段。
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Effect of gut microbiota on depressive-like behaviors in mice is mediated by the endocannabinoid system

内源性大麻素系统介导肠道菌群对小鼠抑郁样行为的影响

10.1038/s41467-020-19931-2

2020-12-11, Article

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Depression is the leading cause of disability worldwide. Recent observations have revealed an association between mood disorders and alterations of the intestinal microbiota. Here, using unpredictable chronic mild stress (UCMS) as a mouse model of depression, we show that UCMS mice display phenotypic alterations, which could be transferred from UCMS donors to naïve recipient mice by fecal microbiota transplantation. The cellular and behavioral alterations observed in recipient mice were accompanied by a decrease in the endocannabinoid (eCB) signaling due to lower peripheral levels of fatty acid precursors of eCB ligands. The adverse effects of UCMS-transferred microbiota were alleviated by selectively enhancing the central eCB or by complementation with a strain of the Lactobacilli genus. Our findings provide a mechanistic scenario for how chronic stress, diet and gut microbiota generate a pathological feed-forward loop that contributes to despair behavior via the central eCB system.

First Authors:
Grégoire Chevalier

Correspondence Authors:
Gabriel Lepousez,Gerard Eberl,Pierre-Marie Lledo

All Authors:
Grégoire Chevalier,Eleni Siopi,Laure Guenin-Macé,Maud Pascal,Thomas Laval,Aline Rifflet,Ivo Gomperts Boneca,Caroline Demangel,Benoit Colsch,Alain Pruvost,Emeline Chu-Van,Aurélie Messager,François Leulier,Gabriel Lepousez,Gerard Eberl,Pierre-Marie Lledo

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