Fecal Microbiota Transplantation from Methionine-Restricted Diet Mouse Donors Improves Alzheimer's Learning and Memory Abilities Through Short-Chain Fatty Acids.

IF 4.7 2区 农林科学 Q1 FOOD SCIENCE & TECHNOLOGY
Foods Pub Date : 2025-01-02 DOI:10.3390/foods14010101
Run Yu, Haimeng Zhang, Rui Chen, Yangzhuo Lin, Jingxuan Xu, Ziyang Fang, Yuehang Ru, Chenhan Fan, Guoqing Wu
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Abstract

Alzheimer's disease (AD) is marked by impaired cognitive functions, particularly in learning and memory, owing to complex and diverse mechanisms. Methionine restriction (MR) has been found to exert a mitigating effect on brain oxidative stress to improve AD. However, the bidirectional crosstalk between the gut and brain through which MR enhances learning and memory in AD, as well as the effects of fecal microbiota transplantation (FMT) from MR mice on AD mice, remains underexplored. In this study, APP/PS1 double transgenic AD mice were used and an FMT experiment was conducted. 16S rRNA gene sequencing, targeted metabolomics, and microbial metabolite short-chain fatty acids (SCFAs) of feces samples were analyzed. The results showed that MR reversed the reduction in SCFAs induced by AD, and further activated the free fatty acid receptors, FFAR2 and FFAR3, as well as the transport protein MCT1, thereby signaling to the brain to mitigate inflammation and enhance the learning and memory capabilities. Furthermore, the FMT experiment from methionine-restricted diet mouse donors showed that mice receiving FMT ameliorated Alzheimer's learning and memory ability through SCFAs. This study offers novel non-pharmaceutical intervention strategies for AD prevention.

来自蛋氨酸限制饮食小鼠供体的粪便微生物群移植通过短链脂肪酸改善阿尔茨海默氏症的学习和记忆能力。
阿尔茨海默病(AD)的特点是认知功能受损,特别是学习和记忆功能受损,其机制复杂多样。蛋氨酸限制(MR)已被发现对脑氧化应激起到缓解作用,以改善阿尔茨海默病。然而,MR增强AD小鼠学习和记忆的肠道和大脑之间的双向串扰,以及MR小鼠粪便微生物群移植(FMT)对AD小鼠的影响,仍未得到充分探讨。本研究采用APP/PS1双转基因AD小鼠,进行FMT实验。对粪便样本的16S rRNA基因测序、靶向代谢组学和微生物代谢物短链脂肪酸(SCFAs)进行分析。结果表明,MR逆转了AD诱导的SCFAs减少,并进一步激活游离脂肪酸受体FFAR2和FFAR3以及转运蛋白MCT1,从而向大脑发出信号,减轻炎症,增强学习和记忆能力。此外,来自蛋氨酸限制饮食小鼠供体的FMT实验表明,接受FMT的小鼠通过scfa改善了阿尔茨海默氏症的学习和记忆能力。本研究为阿尔茨海默病的预防提供了新的非药物干预策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Foods
Foods Immunology and Microbiology-Microbiology
CiteScore
7.40
自引率
15.40%
发文量
3516
审稿时长
15.83 days
期刊介绍: Foods (ISSN 2304-8158) is an international, peer-reviewed scientific open access journal which provides an advanced forum for studies related to all aspects of food research. It publishes reviews, regular research papers and short communications. Our aim is to encourage scientists, researchers, and other food professionals to publish their experimental and theoretical results in as much detail as possible or share their knowledge with as much readers unlimitedly as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. There are, in addition, unique features of this journal: Ÿ manuscripts regarding research proposals and research ideas will be particularly welcomed Ÿ electronic files or software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material Ÿ we also accept manuscripts communicating to a broader audience with regard to research projects financed with public funds
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