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

• Published in: Neural regeneration research Vol. 19; no. 10; pp. 2281 - 2289
• Main Authors: Liao, Wang, Wei, Jiana, Liu, Chongxu, Luo, Haoyu, Ruan, Yuting, Mai, Yingren, Yu, Qun, Cao, Zhiyu, Xu, Jiaxin, Zheng, Dong, Sheng, Zonghai, Zhou, Xianju, Liu, Jun
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer - Medknow 01.10.2024; Medknow Publications & Media Pvt. Ltd; Special Medical Service Center,Neuroscience Center,Integrated Hospital of Traditional Chinese Medicine,Southern Medical University,Guangdong,Guangdong Province,China%Department of Rehabilitation,The Second Affiliated Hospital,Guangzhou Medical University,Guangzhou,Guangdong Province,China%Department of Neurology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou,Guangdong Province,China%Department of Neurology,The Affiliated Brain Hospital of Guangzhou Medical University,Guangzhou,Guangdong Province,China%Institute of Biomedical and Health Engineering,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,Guangdong Province,China%Special Medical Service Center,Neuroscience Center,Integrated Hospital of Traditional Chinese Medicine,Southern Medical University,Guangdong,Guangdong Province,China; Department of Neurology,The Second Affiliated Hospital of Guangzhou Medical University,Guangzhou,Guangdong Province,China%Department of Neurology,The Second Affiliated Hospital of Guangzhou Medical University,Guangzhou,Guangdong Province,China; Wolters Kluwer Medknow Publications
• Edition: 2
• Subjects: Alzheimer's disease; 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; Disease; Gut-brain axis; Microbiota; Research Article; serum metabolites; magnesium-L-threonate; inflammation; microbiota-gut-brain axis; APP/PS1 double-transgenic Alzheimer's disease mouse model; intestinal barrier dysfunction; Alzheimer's disease; microbiome; oxidative stress
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.391310

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 rRNA amplicon sequencing and liquid chromatography-mass spectrometry to analyze changes in the microbiome and serum metabolome following magnesium-L-threonate 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 magnesium-L-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.