Impact of prebiotics on metabolic and behavioral alterations in a mouse model of metabolic syndrome
Impact of prebiotics on metabolic and behavioral alterations in a mouse model of metabolic syndrome
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DOI：
10.1016/j.bbi.2016.12.022
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发表时间：
2017-08-01
影响因子：
15.1
通讯作者：
Castanon, Nathalie
中科院分区：
文献类型：
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作者：
de Cossio, Lourdes Fernandez;Fourrier, Celia;Castanon, Nathalie
越来越多的证据表明，肠道微生物区系是肠道-大脑通信轴的重要参与者，可以影响新陈代谢、炎症、大脑功能和行为。有趣的是，代谢综合征(METS)患者的肠道微生物区系组成已知会发生变化，他们也经常表现出神经精神症状。因此，使用益生菌可以有益地改变微生物区系，因此可能是一种潜在地改善METS患者身心健康的有希望的方法。这一假设在METS的小鼠模型中进行了测试，即肥胖和2型糖尿病dbldb小鼠，与其瘦小的db/+胎相比，这些小鼠表现出与肠道微生物区系组成和海马炎症相关的情绪和认知变化。我们评估了长期服用益生元(低聚果糖)(8周)对dbldb小鼠的代谢(体重、食物摄入量、葡萄糖稳态)和行为(焦虑样行为增加和空间记忆受损)改变的影响，以及相关的神经生物学相关因素，特别是对神经炎症过程的关注。益生元治疗改善了dbldb小鼠的过量食物摄入和血糖调节失调(葡萄糖耐量和胰岛素抵抗)。伴随着血浆抗炎细胞因子IL-10水平和下丘脑厌食性细胞因子IL-18的mRNA表达增加，而下丘脑厌食性(NPY)和厌食性(CART，POMC)多肽的mRNA表达不变。我们还检测到低聚果糖治疗的dbldb小鼠下丘脑血脑屏障完整性改善的迹象(紧密连接蛋白ZO-1和occludin的正常表达)。相反，益生素给药并没有改善db/db小鼠表现出的行为改变和相关的海马神经发生减少，尽管海马区IL-6mRNA的表达正常。值得注意的是，我们发现治疗对齿状回神经元的影响与空间记忆之间存在关系。这些发现可能被证明是有价值的，可以引入新的方法来治疗与METS相关的一些共病。(C)2016 Elsevier Inc.保留所有权利。
Mounting evidence shows that the gut microbiota, an important player within the gut-brain communication axis, can affect metabolism, inflammation, brain function and behavior. Interestingly, gut micro biota composition is known to be altered in patients with metabolic syndrome (MetS), who also often display neuropsychiatric symptoms. The use of prebiotics, which beneficially alters the microbiota, may therefore be a promising way to potentially improve physical and mental health in MetS patients.This hypothesis was tested in a mouse model of MetS, namely the obese and type-2 diabetic dbldb mice, which display emotional and cognitive alterations associated with changes in gut microbiota composition and hippocampal inflammation compared to their lean db/+ littermates. We assessed the impact of chronic administration (8 weeks) of prebiotics (oligofructose) on both metabolic (body weight, food intake, glucose homeostasis) and behavioral (increased anxiety-like behavior and impaired spatial memory) alterations characterizing dbldb mice, as well as related neurobiological correlates, with particular attention to neuroinflammatory processes.Prebiotic administration improved excessive food intake and glycemic dysregulations (glucose tolerance and insulin resistance) in dbldb mice. This was accompanied by an increase of plasma antiinflammatory cytokine IL-10 levels and hypothalamic mRNA expression of the anorexigenic cytokine IL-18, whereas unbalanced mRNA expression of hypothalamic orexigenic (NPY) and anorexigenic (CART, POMC) peptides was unchanged. We also detected signs of improved blood-brain-barrier integrity in the hypothalamus of oligofructose-treated dbldb mice (normalized expression of tight junction proteins ZO-1 and occludin). On the contrary, prebiotic administration did not improve behavioral alterations and associated reduction of hippocampal neurogenesis displayed by db/db mice, despite normalization of increased hippocampal IL-6 mRNA expression. Of note, we found a relationship between the effect of treatment on dentate gyrus neurons and spatial memory. These findings may prove valuable for introducing novel approaches to treat some of the comorbidities associated with MetS. (C) 2016 Elsevier Inc. All rights reserved.