Obesity Impairs Short-Term and Working Memory through Gut Microbial Metabolism of Aromatic Amino Acids
Obesity Impairs Short-Term and Working Memory through Gut Microbial Metabolism of Aromatic Amino Acids
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DOI：
10.1016/j.cmet.2020.09.002
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发表时间：
2020-10-06
期刊：
影响因子：
29
通讯作者：
Fernandez-Real, Jose Manuel
中科院分区：
文献类型：
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作者：
Arnoriaga-Rodriguez, Maria;Mayneris-Perxachs, Jordi;Fernandez-Real, Jose Manuel
肠道微生物组与动物模型中的恐惧灭绝学习有关。在这里，我们的目的是根据肥胖状态探索肠道微生物组和记忆域。一个特定的微生物组概况与短期记忆，工作记忆，以及海马体和大脑额叶区的体积差异在人类受试者和不肥胖。血浆和粪便中芳香族氨基酸、其代谢产物和植物衍生化合物的水平与短期记忆和工作记忆纵向相关。从功能上讲，从肥胖的人类受试者身上移植的微生物群导致小鼠的记忆力评分下降，使人类的这一特征与受体小鼠的这一特征相一致。对小鼠内侧前额叶皮层的RNA测序显示，短期记忆与芳香族氨基酸途径、炎症基因和细菌物种簇有关。这些结果突出了靶向肠道微生物群对记忆障碍的潜在治疗价值，特别是在肥胖受试者中。
The gut microbiome has been linked to fear extinction learning in animal models. Here, we aimed to explore the gut microbiome and memory domains according to obesity status. A specific microbiome profile associated with short-term memory, working memory, and the volume of the hippocampus and frontal regions of the brain differentially in human subjects with and without obesity. Plasma and fecal levels of aromatic amino acids, their catabolites, and vegetable-derived compounds were longitudinally associated with short-term and working memory. Functionally, microbiota transplantation from human subjects with obesity led to decreased memory scores in mice, aligning this trait from humans with that of recipient mice. RNA sequencing of the medial prefrontal cortex of mice revealed that short-term memory associated with aromatic amino acid pathways, inflammatory genes, and clusters of bacterial species. These results highlight the potential therapeutic value of targeting the gut microbiota for memory impairment, specifically in subjects with obesity.