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通过代谢组学、金属组学、基因表达和扩增子测序,结合研究硒通过肠脑轴对小鼠大脑代谢组和硒蛋白组的影响。

The role of selenium in shaping mice brain metabolome and selenoproteome through the gut-brain axis by combining metabolomics, metallomics, gene expression, and amplicon sequencing.

机构信息

Department of Chemistry, Faculty of Experimental Sciences, Research Center of Natural Resources, Health and the Environment (RENSMA), University of Huelva, Huelva, Spain.

Department of Biochemistry and Molecular Biology, University of Córdoba, Córdoba, Spain.

出版信息

J Nutr Biochem. 2023 Jul;117:109323. doi: 10.1016/j.jnutbio.2023.109323. Epub 2023 Mar 22.

DOI:10.1016/j.jnutbio.2023.109323
PMID:36958417
Abstract

Selenium (Se) is a trace element crucial for human health. Recently, the impact of Se supplementation on gut microbiota has been pointed out as well as its influence on the expression of certain selenoproteins and gut metabolites. This study aims to elucidate the link between Se supplementation, brain selenoproteins and brain metabolome as well as the possible connection with the gut-brain axis. To this end, an in vivo study with 40 BALB/c mice was carried out. The study included conventional (n=20) and mice model with microbiota depleted by antibiotics (n=20) under a regular or Se supplemented diet. Brain selenoproteome was determined by a transcriptomic/gene expression profile, while brain metabolome and gut microbiota profiles were accomplished by untargeted metabolomics and amplicon sequencing, respectively. The total content of Se in brain was also determined. The selenoproteins genes Dio and Gpx isoenzymes, SelenoH, SelenoI, SelenoT, SelenoV, and SelenoW and 31 metabolites were significantly altered in the brain after Se supplementation in conventional mice, while 11 selenoproteins and 26 metabolites were altered in microbiota depleted mice. The main altered brain metabolites were related to glyoxylate and dicarboxylate metabolism, amino acid metabolism, and gut microbiota that have been previously related with the gut-brain axis (e.g., members of Lachnospiraceae and Ruminococcaceae families). Moreover, specific associations were determined between brain selenoproteome and metabolome, which correlated with the same bacteria, suggesting an intertwined mechanism. Our results demonstrated the effect of Se on brain metabolome through specific selenoproteins gene expression and gut microbiota.

摘要

硒(Se)是一种对人类健康至关重要的微量元素。最近,人们指出硒补充对肠道微生物群的影响,以及它对某些硒蛋白和肠道代谢物表达的影响。本研究旨在阐明硒补充、大脑硒蛋白和大脑代谢组之间的联系,以及与肠道-大脑轴的可能联系。为此,进行了一项包含 40 只 BALB/c 小鼠的体内研究。该研究包括常规(n=20)和抗生素耗尽微生物群的小鼠模型(n=20),在常规或补充硒的饮食下进行。通过转录组/基因表达谱来确定大脑硒蛋白组,而大脑代谢组和肠道微生物组图谱则分别通过非靶向代谢组学和扩增子测序来完成。还测定了大脑中硒的总含量。在常规小鼠中,硒补充后大脑中的 Dio 和 Gpx 同工酶、SelenoH、SelenoI、SelenoT、SelenoV 和 SelenoW 等硒蛋白基因和 31 种代谢物发生了显著变化,而在耗尽微生物群的小鼠中,有 11 种硒蛋白和 26 种代谢物发生了变化。主要改变的大脑代谢物与乙醛酸和二羧酸代谢、氨基酸代谢以及与肠道-大脑轴相关的肠道微生物群有关(例如,Lachnospiraceae 和 Ruminococcaceae 家族的成员)。此外,还确定了大脑硒蛋白组和代谢组之间的特定关联,这些关联与相同的细菌相关,表明存在一种交织的机制。我们的结果表明,硒通过特定的硒蛋白基因表达和肠道微生物群对大脑代谢组产生影响。

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