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Alterations in the gut microbiota contribute to cognitive impairment induced by the ketogenic diet and hypoxia
Cell Host & Microbe ( IF 30.3 ) Pub Date : 2021-08-05 , DOI: 10.1016/j.chom.2021.07.004
Christine A Olson 1 , Alonso J Iñiguez 1 , Grace E Yang 1 , Ping Fang 1 , Geoffrey N Pronovost 1 , Kelly G Jameson 1 , Tomiko K Rendon 1 , Jorge Paramo 1 , Jacob T Barlow 2 , Rustem F Ismagilov 2 , Elaine Y Hsiao 1
Affiliation  

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 potentiates CI induced by intermittent hypoxia in mice and alters the gut microbiota. Depleting the microbiome reduces 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.



中文翻译:

肠道微生物群的改变导致生酮饮食和缺氧引起的认知障碍

许多遗传和环境因素增加了对认知障碍 ( CI ) 的易感性,肠道微生物群越来越受到牵连。然而,与 CI 风险相关的肠道微生物的特性、它们对 CI 的影响及其机制仍不清楚。在这里,我们表明限制碳水化合物(生酮)饮食会增强小鼠间歇性缺氧引起的 CI,并改变肠道微生物群。耗尽微生物组可降低 CI,而风险相关微生物组的移植或Bilophila wadsworthia的单克隆化可使喂食标准饮食的小鼠出现 CI。B. wadsworthia与风险相关的微生物组会破坏海马突触可塑性、神经发生和基因表达。CI 与产生肠道干扰素-γ (IFNg) 的 Th1 细胞的微生物组依赖性增加有关。抑制 Th1 细胞发育消除了B. wadsworthia和环境风险因素对 CI 的不利影响。总之,这些发现确定了特定的肠道细菌,这些细菌通过促进炎症和海马功能障碍而导致小鼠 CI 的环境风险。

更新日期:2021-09-08
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