Altered colonic function and microbiota profile in a mouse model of chronic depression.
Altered colonic function and microbiota profile in a mouse model of chronic depression.
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DOI：
10.1111/nmo.12153
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发表时间：
2013-09
影响因子：
3.5
通讯作者：
Collins SM
中科院分区：
文献类型：
--
作者：
Park AJ;Collins J;Blennerhassett PA;Ghia JE;Verdu EF;Bercik P;Collins SM
背景抑郁症常与肠易激综合征（IBS）并存，IBS的特征是肠道功能的改变。 有新的证据表明肠道的微生物组成（微生物群）在IBS中发生了改变，但对此的基础知之甚少。本研究的目的是确定慢性抑郁症的诱导是否会导致结肠功能及其微生物群落的变化，并探索潜在的机制。方法采用双侧嗅球切除术（OBx）诱导小鼠抑郁样行为。 通过测量肌肉收缩力、颗粒排泄、c-fos活性和5-羟色胺水平来评估结肠功能。使用变性梯度凝胶电泳（DGGE）获得微生物群谱。通过下丘脑促肾上腺皮质激素释放激素（CRH）的表达来评估下丘脑-垂体轴（HPA）。在单独的研究中，没有OBx的小鼠在评估结肠功能和微生物群特征之前通过脑室内（ICV）输注接受CRH 4周。 嗅球切除小鼠表现出慢性抑郁和焦虑样行为，与中枢CRH表达升高和c-Fos活性、5-羟色胺水平和结肠运动性增加相关。这些变化伴随着肠道微生物谱的改变。中央CRH给药在行为和运动方面产生了类似的变化，并改变了结肠中的微生物群。结论和推论慢性抑郁症的诱导可能通过激活HPA改变结肠中的运动活动和微生物概况。 这些发现为IBS的行为和胃肠道表现之间的联系提供了基础。
Background Depression often coexists with the irritable bowel syndrome (IBS) which is characterized by alterations in gut function. There is emerging evidence that the microbial composition (microbiota) of the gut is altered in IBS, but the basis for this is poorly understood. The aim of this study was to determine whether the induction of chronic depression results in changes in the colonic function and in its microbial community, and to explore underlying mechanisms. Methods Bilateral olfactory bulbectomy (OBx) was used to induce depression-like behavior in mice. Colonic function was assessed by measuring muscle contractility, pellet excretion, c-fos activity, and serotonin levels. Microbiota profiles were obtained using denaturing gradient gel electrophoresis (DGGE). The hypothalamic-pituitary axis (HPA) was assessed by the hypothalamic expression of corticotropin-releasing hormone (CRH). In separate studies, mice without OBx received CRH via intracerebroventricular (ICV) infusion for 4 weeks prior to assessing colonic function and microbiota profiles. Key Results Olfactory bulbectomy mice demonstrated chronic depression- and anxiety-like behaviors associated with elevated central CRH expression and increases in c-Fos activity, serotonin levels, and motility in the colon. These changes were accompanied by an altered intestinal microbial profile. Central CRH administration produced similar changes in behavior and motility and altered the microbiota profile in the colon. Conclusions & Inferences The induction of chronic depression alters motor activity and the microbial profile in the colon likely via activation of the HPA. These findings provide a basis for linking the behavioral and gastrointestinal manifestations of IBS.
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