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

作　　者：Wang Liao Jiana Wei Chongxu Liu Haoyu Luo Yuting Ruan Yingren Mai Qun Yu Zhiyu Cao Jiaxin Xu Dong Zheng Zonghai Sheng Xianju Zhou Jun Liu 

机构地区：[1]Department of Neurology,The Second Affiliated Hospital of Guangzhou Medical University,Guangzhou,Guangdong Province,China [2]Special Medical Service Center,Neuroscience Center,Integrated Hospital of Traditional Chinese Medicine,Southern Medical University,Guangdong,Guangdong Province,China [3]Department of Rehabilitation,The Second Affiliated Hospital,Guangzhou Medical University,Guangzhou,Guangdong Province,China [4]Department of Neurology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou,Guangdong Province,China [5]Department of Neurology,The Affiliated Brain Hospital of Guangzhou Medical University,Guangzhou,Guangdong Province,China [6]Institute of Biomedical and Health Engineering,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,Guangdong Province,China

出　　处：《Neural Regeneration Research》2024年第10期2281-2289,共9页中国神经再生研究（英文版）

基　　金：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);Technology Key Project of Shenzhen,No.JCYJ202001091 14612308 (to ZS)。

摘　　要：Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer's disease. Magnesium-L-threonate has recently been found to have protective effects on learning and memory in aged and Alzheimer's disease model mice. However, the effects of magnesium-L-threonate on the gut microbiota in Alzheimer's disease remain unknown. Previously, we reported that magnesium-L-threonate treatment improved cognition and reduced oxidative stress and inflammation in a double-transgenic line of Alzheimer's disease model mice expressing the amyloid-β precursor protein and mutant human presenilin 1(APP/PS1). Here, we performed 16S r RNA amplicon sequencing and liquid chromatography-mass spectrometry to analyze changes in the microbiome and serum metabolome following magnesium-Lthreonate exposure in a similar mouse model. Magnesium-L-threonate 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 magnesiumL-threonate-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 magnesium-L-threonate repaired the intestinal barrier dysfunction of APP/PS1 mice. These findings suggest that magnesium-L-threonate may reduce the clinical manifestations of Alzheimer's disease through the microbiota-gut-brain axis in model mice, providing an experimental basis for the clinical treatment of Alzheimer's disease.

关 键 词：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 

分 类 号：R749.16[医药卫生—神经病学与精神病学]