Neuroprotective Effect of Mesenchymal Stromal Cells in Alzheimer's Disease Model Mice through gut microbes and their associated metabolites via microbiome-gut-brain axis
This repository contains the scripts to reproduce the result of the manuscript Neuroprotective Effect of Mesenchymal Stromal Cells in Alzheimer's Disease Model Mice through gut microbes and their associated metabolites via microbiome-gut-brain axis
The intricacy and multifaceted nature of Alzheimer's disease (AD) necessitate therapies that target multiple aspects of the disease. Mesenchymal stromal cells (MSCs) emerge as potential agents to mitigate AD symptoms, however, whether their therapeutic efficacy involves modulation of gut microbiota and the microbiome-gut-brain axis (MGBA) remains unexplored. In this study, we evaluated the effects of three distinct MSC types--derived from the umbilical cord (UCMSC), dental pulp (SHED), and adipose tissue (ADSC)--in an APP/PS1 mouse model of AD. MSC administration resulted in a significant reduction of behavioral disturbances, amyloid plaques, and phosphorylated tau in the hippocampus and frontal cortex, accompanied by an increase in neuronal count and Nissl body density across AD-afflicted brain regions, relative to saline control. Through 16S rRNA gene sequencing, we identified partial restoration of gut microbial balance in AD mice post-MSC treatment, evidenced by the elevation of neuroprotective Akkermansia, and the reduction of AD-associated Sphingomonas. Antibiotic-mediated gut microbiota and targeted bile acids metabolism profiling revealed a significant enhancement in bile acid variety following MSCs therapy. A chief bile acid consitiuent, taurocholic acid (TCA), was orally administered to AD mice and similarly abated AD manifestations. Nonetheless, the disruption of intestinal neuronal integrity with enterotoxin abrogated the ameliorative impact of both MSCs and TCA treatments. Collectively, our findings substantiate that MSCs confer therapeutic benefits in AD within a paradigm that primarily involves regulation of gut microbiota and their metabolites through the MGBA.
/qiime_result/: the analysis result of qiime 2 (version2023.09)/qiime_visualization/: the qiime 2 visualization files/data_to_import/: the 16s rRNA sequence (it also could be download from PRJNA1050664)/classify/: the nb classify for qiime2/figures/: the figures of manuscript/pdf/: the figures of manuscript1.qiime2_analysis.ipynb: the reproduce code of qiime2 analysis2.micfunpred_analysis.ipynb: the reproduce code of visualization for micfunpred
- Zehua Zeng (starlitnightly@163.com or zehuazeng@xs.ustb.edu.cn)