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

Neural Regen Res. 2024 Oct 1;19(10):2281-2289. doi: 10.4103/1673-5374.391310. Epub 2023 Dec 21.

Abstract

JOURNAL/nrgr/04.03/01300535-202410000-00029/figure1/v/2024-02-06T055622Z/r/image-tiff 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.

Grants and funding

Funding: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).