Alterations in the gut microbiota contribute to cognitive impairment induced by the ketogenic diet and hypoxia.
Alterations in the gut microbiota contribute to cognitive impairment induced by the ketogenic diet and hypoxia.
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DOI：
10.1016/j.chom.2021.07.004
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发表时间：
2021-09-08
影响因子：
30.3
通讯作者：
Hsiao EY
中科院分区：
文献类型：
--
作者：
Olson CA;Iñiguez AJ;Yang GE;Fang P;Pronovost GN;Jameson KG;Rendon TK;Paramo J;Barlow JT;Ismagilov RF;Hsiao EY
许多遗传和环境因素增加了对认知障碍（CI）的易感性，肠道微生物组的影响越来越大。然而，与CI风险相关的肠道微生物的身份、它们对CI的影响及其机制仍不清楚。本研究表明，限制碳水化合物（生酮）饮食和间歇性缺氧可增强小鼠CI并改变肠道微生物群。消耗微生物组可预防CI，而移植风险相关微生物组或单定殖wadsworth Bilophila可在喂食标准饮食的小鼠中获得CI。B. wadsworthia和风险相关微生物组破坏海马突触可塑性、神经发生和基因表达。CI与肠道干扰素- γ (IFNg)产生的Th1细胞的微生物组依赖性增加有关。抑制Th1细胞发育可消除wadsworthia和环境危险因素对CI的不利影响。总之，这些发现确定了通过促进炎症和海马功能障碍而导致小鼠CI环境风险的肠道细菌。肠道微生物群的改变越来越多地与认知功能障碍有关。Olson等人发现，生酮饮食和缺氧协同损害小鼠的认知行为并改变肠道微生物群。选择风险相关的细菌足以通过免疫介导的途径破坏海马功能和认知行为。
Many genetic and environmental factors increase susceptibility to cognitive impairment (CI), and the gut microbiome is increasingly implicated. However, the identity of gut microbes associated with CI risk, their effects on CI, and their mechanisms remain unclear. Here we show that a carbohydrate-restricted (Ketogenic) diet and intermittent hypoxia in mice potentiates CI and alters the gut microbiota. Depleting the microbiome prevents CI, whereas transplantation of the risk-associated microbiome or monocolonization with Bilophila wadsworthia confers CI in mice fed a standard diet. B. wadsworthia and the risk-associated microbiome disrupt hippocampal synaptic plasticity, neurogenesis, and gene expression. The CI is associated with microbiome-dependent increases in intestinal interferon-gamma (IFNg)-producing Th1 cells. Inhibiting Th1 cell development abrogates the adverse effects of both B. wadsworthia and environmental risk factors on CI. Together, these findings identify select gut bacteria that contribute to environmental risk for CI in mice by promoting inflammation and hippocampal dysfunction. Alterations in the gut microbiome are increasingly implicated in cognitive dysfunction. Olson et al. reveal that ketogenic diet and hypoxia synergistically impair cognitive behavior and modify the gut microbiota in mice. Select risk-associated bacteria are sufficient to disrupt hippocampal function and cognitive behavior via immune-mediated pathways.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
脑膜免疫调节学习和记忆：IL-4 的关键作用。
影响因子：
15.3
作者：
Derecki, Noel C.;Cardani, Amber N.;Yang, Chun Hui;Quinnies, Kayla M.;Crihfield, Anastasia;Lynch, Kevin R.;Kipnis, Jonathan
通讯作者：
Kipnis, Jonathan
SK 通道对 NMDA 受体介导的传递的不同调控是沙弗侧突触功能动态背腹差异的基础
影响因子：
5.3
作者：
Babiec, Walter E.;Jami, Shekib A.;O'Dell, Thomas J.
通讯作者：
O'Dell, Thomas J.
影响因子：
2.5
作者：
Bahr, Lina Samira;Bock, Markus;Maehler, Anja
通讯作者：
Maehler, Anja
影响因子：
5.3
作者：
Badran M;Khalyfa A;Ericsson A;Gozal D
通讯作者：
Gozal D