Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity.
Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity.
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DOI：
10.1016/j.biopsych.2014.07.012
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发表时间：
2015-04-01
影响因子：
10.6
通讯作者：
Berthoud HR
中科院分区：
文献类型：
--
作者：
Bruce-Keller AJ;Salbaum JM;Luo M;Blanchard E 4th;Taylor CM;Welsh DA;Berthoud HR
肥胖会增加精神疾病的患病率，尤其是抑郁症和痴呆症。在此我们检验这样一个假设：肠道微生物群因肥胖而发生的变化本身就能够损害小鼠的神经认知行为。
将常规饲养的、食用正常饲料的非肥胖成年雄性C57BL/6小鼠，采用从高脂肪饮食（HFD）或对照饮食（CD）的供体中分离出的微生物群，进行微生物群清除/移植实验。重新定殖后，对小鼠进行全面的行为和生化分析。
与具有CD微生物群的小鼠相比，接受HFD微生物群的小鼠在探索、认知和刻板行为方面出现了显著且具有选择性的紊乱，而体重并无显著差异。基于测序的系统发育分析证实了各组之间存在不同的核心微生物群，α -多样性和β -多样性发生改变，分类分布受到调节，具有代谢活性的分类群发生了具有统计学意义的改变。HFD微生物群还破坏了肠道屏障功能的标志物，增加了循环内毒素，并增加了Iba1、TLR2和TLR4的淋巴细胞表达。最后，对脑匀浆的评估显示，受HFD影响的微生物群增加了神经炎症并破坏了脑血管内稳态。
总之，这些数据强化了肠道菌群失调与神经功能障碍之间的联系，并表明对肠道微生物群进行饮食和/或药物干预可能减轻肥胖的神经并发症。
The prevalence of mental illness, particularly depression and dementia, is increased by obesity. Here we test the hypothesis that obesity-associated changes in gut microbiota are intrinsically able to impair neurocognitive behavior in mice. Conventionally housed, non-obese, adult male C57BL/6 mice maintained on a normal chow diet were subjected to a microbiome depletion/transplantation paradigm using microbiota isolated from donors (given) on either high-fat (HFD) or control diet (CD). Following recolonization, mice were subjected to comprehensive behavioral and biochemical analyses. The mice given HFD microbiota had significant and selective disruptions in exploratory, cognitive, and stereotypical behavior compared to mice with CD microbiota in the absence of significant differences in body weight. Sequencing-based phylogenetic analysis confirmed the presence of distinct core microbiota between groups, with alterations in α- and β- diversity, modulation in taxonomic distribution, and statistically significant alterations to metabolically active taxa. HFD microbiota also disrupted markers of intestinal barrier function, increased circulating endotoxin, and increased lymphocyte expression of Iba1, TLR2, and TLR4. Finally, evaluation of brain homogenates revealed that HFD-shaped microbiota increased neuroinflammation and disrupted cerebrovascular homeostasis. Collectively, these data reinforce the link between gut dysbiosis and neurologic dysfunction and suggest that dietary and/or pharmacological manipulation of gut microbiota could attenuate the neurologic complications of obesity.