Depletion of gut microbiota resistance in 5×FAD mice enhances the therapeutic effect of mesenchymal stem cell-derived exosomes

Xuejia Hou; Hongyu Jiang; Te Liu; Jun Yan; Fuqiang Zhang; Xiaowen Zhang; Jingtong Zhao; Xupeng Mu; Jinlan Jiang

doi:10.1016/j.biopha.2023.114455

Depletion of gut microbiota resistance in 5×FAD mice enhances the therapeutic effect of mesenchymal stem cell-derived exosomes

Biomed Pharmacother. 2023 May:161:114455. doi: 10.1016/j.biopha.2023.114455. Epub 2023 Mar 9.

Authors

Xuejia Hou¹, Hongyu Jiang², Te Liu³, Jun Yan¹, Fuqiang Zhang¹, Xiaowen Zhang¹, Jingtong Zhao¹, Xupeng Mu⁴, Jinlan Jiang⁵

Affiliations

¹ Scientifc Research Center, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130033, Jilin, China.
² Life Spring AKY Pharmaceuticals, Changchun 130033, Jilin, China.
³ Scientifc Research Center, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130033, Jilin, China; Yibin Jilin University Research Institute, Jilin University, Yibin, Sichuan, China.
⁴ Scientifc Research Center, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130033, Jilin, China. Electronic address: muxupeng@jlu.edu.cn.
⁵ Scientifc Research Center, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130033, Jilin, China. Electronic address: jiangjinlan@jlu.edu.cn.

PMID: 36905811
DOI: 10.1016/j.biopha.2023.114455

Abstract

Mesenchymal stem cell-derived exosomes (MSCs-exo) can be used for treating Alzheimer's disease (AD) by promoting amyloid-β (Aβ) degradation, modulating immune responses, protecting neurology, promoting axonal growth, and improving cognitive impairment. Increasing evidence suggests that the alteration of gut microbiota is closely related to the occurrence and development of Alzheimer's disease. In this study, we hypothesized that dysbiosis of gut microbiota might limit the therapy of MSCs-exo, and the application of antibiotics would improve the therapy.

Methods: In this original research study, we used MSCs-exo to treat 5 ×FAD mice and fed them antibiotic cocktails for 1 week to detect cognitive ability and neuropathy. The mice's feces were collected to investigate alterations in the microbiota and metabolites.

Results: The results revealed that the AD gut microbiota eliminated the therapeutic effect of MSCs-exo, whereas antibiotic modulation of disordered gut microbiota and associated metabolites enhanced the therapeutic effect of MSCs-exo.

Conclusions: These results encourage the research of novel therapeutics to enhance MSCs-exo treatment for AD, which could benefit a broader range of patients with AD.

Keywords: Alzheimer’s disease; Broad-spectrum antibiotics; Exosomes; Gut microbiota; Mesenchymal stem cells.

MeSH terms

Alzheimer Disease* / metabolism
Alzheimer Disease* / therapy
Animals
Anti-Bacterial Agents / metabolism
Anti-Bacterial Agents / pharmacology
Exosomes* / metabolism
Gastrointestinal Microbiome*
Mesenchymal Stem Cells* / metabolism
Mice

Substances

Anti-Bacterial Agents