中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (on line): 1-6.

• •    下一篇

Magnesium-L-threonate treats Alzheimer’s disease by modulating the microbiota-gut-brain axis

  

  • 出版日期:2024-01-01 发布日期:2023-11-17

Wang Liao1, #, Jiana Wei1, 6, #, Chongxu Liu1, #, Haoyu Luo1, Yuting Ruan2, Yingren Mai1, Qun Yu3, Zhiyu Cao3, Jiaxin Xu3, Dong Zheng4, Zonghai Sheng5, Xianju Zhou6, *, Jun Liu1, *   

  1. 1Department of Neurology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China; 2Department of Rehabilitation, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, China; 3Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China; 4Department of Neurology, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China; 5Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong Province, China; 6Special Medical Service Center, Neuroscience Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangdong, Guangdong Province, China
  • Online:2024-01-01 Published:2023-11-17
  • Contact: Xianju Zhou, PhD, xianjuzhou2022@163.com; Jun Liu, PhD, liujun@gzhmu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 82101271 (to WL), 82171178 (to JL); Basic and Applied Basic Research Foundation of Guangdong Province, Nos. 2020A1515110317 (to WL), 2021A1515010705 (to WL); Young Talent Support Project of Guangzhou Association for Science and Technology (to WL) and Technology Key Project of Shenzhen, No. JCYJ20200109114612308 (to ZS).

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摘要： https://orcid.org/0000-0003-0526-3523 (Jun Liu); https://orcid.org/0000-0003-1744-556X (Xianju Zhou)

Abstract: Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer’s disease (AD). Magnesium-L-threonate (MgT) has recently been found to have protective effects on learning and memory in aged and AD model mice. However, the effects of MgT on the gut microbiota in AD remain unknown. Previously, we reported that MgT treatment improved cognition and reduced oxidative stress and inflammation in a double-transgenic line of AD model mice expressing the amyloid-β precursor protein and mutant human presenilin 1 (APP/PS1). Here, we performed 16S rRNA amplicon sequencing and liquid chromatography-mass spectrometry to analyze changes in the microbiome and serum metabolome following MgT exposure in a similar mouse model. MgT modulated the abundance of three genera in the gut microbiota, decreasing Allobaculum and increasing Bifidobacterium and Turicibacter. We also found that differential metabolites in the MgT-regulated serum were enriched in various pathways associated with neurodegenerative diseases. The western blotting detection on intestinal tight junction proteins (zona occludens 1, occludin, and claudin-5) showed that MgT repaired the intestinal barrier dysfunction of APP/PS1 mice. These findings suggest that MgT may reduce the clinical manifestations of AD through the microbiota-gut-brain axis in model mice, providing an experimental basis for the clinical treatment of AD. 

Key words: Alzheimer’s disease, APP/PS1 double-transgenic Alzheimer’s disease mouse model, inflammation, intestinal barrier dysfunction, magnesium-L-threonate, microbiome, microbiota-gut-brain axis, oxidative stress, serum metabolites