The effects of chronic unpredicted mild stress on maternal negative emotions and gut microbiota and metabolites in pregnant rats.
The effects of chronic unpredicted mild stress on maternal negative emotions and gut microbiota and metabolites in pregnant rats.
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作者：
Wang R;Zhao F;Li Y;Zhu J;Liu Y;Li J;Yao G;Liu H;Guan S;Ma S
慢性长期压力与一系列疾病有关，包括抑郁症和其他各种慢性疾病。众所周知，母亲在怀孕期间受到心理社会压力会大大增加不良妊娠结果的可能性。肠道菌群一直是一个热门话题，它是肠-脑轴的关键介质，在人类健康中起着重要作用;肠道菌群的变化与慢性应激诱导的健康损害有关，然而，母体在妊娠期间暴露于慢性应激时的负面情绪与异常肠道菌群及其代谢产物之间的关系尚不清楚。对孕鼠进行慢性不可预见的轻度应激（CIMs），建立孕鼠慢性应激模型。采用蔗糖偏好试验（SPT）和旷场试验（OFT）记录行为学变化，放射免疫法测定血浆皮质酮水平，并采用16 S rRNA基因测序和气相色谱-质谱（GC-MS）代谢组学相结合的综合方法研究妊娠期应激对肠道菌群及其代谢产物功能的影响。妊娠期慢性应激不仅使母体血浆皮质酮水平升高（P < 0.05），而且可引起母体抑郁样行为（P < 0.05）。妊娠期慢性应激改变了母体肠道菌群在科水平上的物种组成，应激组瘤胃球菌科的物种丰度（23.45%）低于对照组（32.67%），而普雷沃氏菌科的物种丰度（10.45%）高于对照组（0.03%）（P < 0.05）。孕鼠垂直运动和1%蔗糖偏好率与普雷沃氏菌呈负相关（r =-0.90，P < 0.05）。主成分分析结合偏最小二乘判别分析显示，应激组和对照组代谢组分的积分点完全分离，说明两组代谢模式存在显著差异，有7种内源性代谢产物存在差异（P <0. 05）。由于产前慢性应激而发生在怀孕大鼠中的负面情绪行为可能与肠道微生物群及其代谢产物的改变有关。这些发现为将来针对妊娠期间慢性应激对肠道植物群影响的代谢组学和肠道植物群研究提供了基础。
Chronic long-term stress is associated with a range of disorders, including depression and a variety of other chronic illnesses. It is well known that maternal exposure to psychosocial stress during pregnancy significantly increases the likelihood of adverse pregnancy outcomes. The gut microbiota has been a popular topic, it is a key mediator of the gut-brain axis and plays an important role in human health; changes in the gut microbiota have been related to chronic stress-induced health impairment, however, the relationship between maternal negative emotions and abnormal gut microbiota and its metabolites during maternal exposure to chronic stress during pregnancy remains unclear. Pregnant rats were subjected to chronic unpredicted mild stress (CUMS) to establish the rat model of chronic stress during pregnancy. The behavioral changes were recorded using sucrose preference test (SPT) and open-field test (OFT), plasma corticosterone levels were determined by radioimmunoassay, and a comprehensive method combining 16S rRNA gene sequencing and gas chromatography-mass spectrometry (GC-MS) metabolomics was used to study the effects of stress during pregnancy on the function of intestinal microbiota and its metabolites. Chronic stress during pregnancy not only increased maternal plasma corticosterone (P < 0.05), but also caused maternal depression-like behaviors (P < 0.05). Chronic stress during pregnancy changed the species composition at the family level of maternal gut microbiota, the species abundance of Ruminococcaceae in the stress group (23.45%) was lower than the control group (32.67%) and the species abundance of Prevotellaceae in the stress group (10.45%) was higher than the control group (0.03%) (P < 0.05). Vertical locomotion and 1% sucrose preference percentage in pregnant rats were negatively correlated with Prevotellaceae (r = − 0.90, P < 0.05). Principal component analysis with partial least squares discriminant analysis showed that the integration points of metabolic components in the stress and control groups were completely separated, indicating that there were significant differences in the metabolic patterns of the two groups, and there were seven endogenous metabolites that differed (P < 0.05). The negative emotional behaviors that occur in pregnant rats as a result of prenatal chronic stress may be associated with alterations in the gut microbiota and its metabolites. These findings provide a basis for future targeted metabolomics and gut flora studies on the effects of chronic stress during pregnancy on gut flora.
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DOI：
10.1016/j.socscimed.2017.01.023
发表时间：
2017-03
期刊：
Social science & medicine (1982)
影响因子：
--
作者：
Hjelm L;Handa S;de Hoop J;Palermo T;Zambia CGP and MCP Evaluation Teams
通讯作者：
Zambia CGP and MCP Evaluation Teams
影响因子：
64.8
作者：
Glenwright AJ;Pothula KR;Bhamidimarri SP;Chorev DS;Baslé A;Firbank SJ;Zheng H;Robinson CV;Winterhalter M;Kleinekathöfer U;Bolam DN;van den Berg B
通讯作者：
van den Berg B
影响因子：
10.5
作者：
ADERIBIGBE, YA;GUREJE, O;OMIGBODUN, O
通讯作者：
OMIGBODUN, O
影响因子：
2.3
作者：
Kang, Dae-Wook;Ilhan, Zehra Esra;Krajmalnik-Brown, Rosa
通讯作者：
Krajmalnik-Brown, Rosa
影响因子：
5.6
作者：
Kelly, John R.;Clarke, Gerard;Dinan, Timothy G.
通讯作者：
Dinan, Timothy G.