Selenium Intervention in Alzheimer's Disease Mice and Its Possible Involvement of the Gut-Brain Axis

Alzheimer's disease (AD) is a neurodegenerative disease closely associated with alterations in the gut microbiota (GM). The impact on GM may be one of the mechanisms by which selenium (Se) prevents and treats AD. This study investigated the effects of sodium selenite interventions on GM-driven metabolic changes and microbiome-gut-brain axis (MGBA) communication in triple transgenic AD mice (3×Tg-AD) using 16S rDNA sequencing and metabolomics. The results demonstrated that Se intervention significantly altered the GM of AD mice, with notable enhancement in pathways related to amino acid metabolism (tyrosine and phenylalanine metabolism, tryptophan metabolism) and lipid metabolism (glycerol degradation). Metabolomics analysis identified 119 differentially expressed metabolites (DEMs) in gut contents, 42 in serum, and 63 in the cortex, which were involved in metabolic pathways such as arachidonic acid metabolism, bile acid biosynthesis, and phospholipid biosynthesis. Correlation analysis revealed that Family_XIII_AD3011_group and Alistipes, identified as key microbiotas, were significantly associated with multiple DEMs in peripheral to central brain tissue. Moreover, lipid metabolites exhibited close relationships with various tissues. These findings indicate that Se intervention increases the abundance of certain beneficial bacteria while suppressing harmful ones in the gut and affecting metabolic pathways, thereby improving cognitive function and pathological features in 3×Tg-AD mice.阿尔茨海默病（Alzheimer's disease, AD）是一种与肠道菌群（gut microbiota, GM）结构紊乱密切相关的神经退行性疾病。硒（selenium, Se）对肠道菌群的调控作用，可能是其防治阿尔茨海默病的核心机制之一。本研究以三转基因阿尔茨海默病小鼠（triple transgenic AD mice, 3×Tg-AD）为模型，采用16S核糖体DNA（16S rDNA）测序与代谢组学技术，探究了亚硒酸钠干预对肠道菌群介导的代谢改变以及微生物群-肠-脑轴（microbiome-gut-brain axis, MGBA）信号交流的影响。研究结果显示，亚硒酸钠干预可显著改变阿尔茨海默病小鼠的肠道菌群结构，显著增强氨基酸代谢（酪氨酸、苯丙氨酸代谢及色氨酸代谢）与脂质代谢（甘油降解）相关通路的活性。代谢组学分析共鉴定出119种肠道内容物差异表达代谢物（differentially expressed metabolites, DEMs）、42种血清差异表达代谢物及63种皮层差异表达代谢物，这些代谢物参与花生四烯酸代谢、胆汁酸生物合成及磷脂生物合成等多条代谢通路。相关性分析表明，被鉴定为核心菌群的Family_XIII_AD3011_group与别样杆菌属（Alistipes），与外周组织至中枢脑组织中的多种差异表达代谢物均存在显著关联；此外，脂质代谢物与多种组织均呈现紧密联系。本研究结果提示，亚硒酸钠干预可通过提升肠道内有益菌丰度、抑制有害菌增殖，并调控相关代谢通路，从而改善三转基因阿尔茨海默病小鼠的认知功能与病理特征。

搜集汇总

背景与挑战

背景概述

该数据集总结了硒干预在阿尔茨海默病（AD）小鼠模型中的作用，重点探讨了硒通过调节肠道菌群和代谢途径（如氨基酸和脂质代谢）来改善认知功能和病理特征的潜在机制。研究发现，硒干预显著改变了AD小鼠的肠道菌群组成，并识别了多个与微生物群-肠-脑轴相关的差异表达代谢物，揭示了硒可能通过影响微生物群-肠-脑轴来治疗AD。