Advances in the study of the effects of gut microflora on microglia in Alzheimer's disease

Front Mol Neurosci. 2023 Nov 30:16:1295916. doi: 10.3389/fnmol.2023.1295916. eCollection 2023.

Abstract

Alzheimer's disease (AD) is a central nervous system (CNS) degenerative disorder, is caused by various factors including β-amyloid toxicity, hyperphosphorylation of tau protein, oxidative stress, and others. The dysfunction of microglia has been associated with the onset and advancement of different neurodevelopmental and neurodegenerative disorders, such as AD. The gut of mammals harbors a vast and complex population of microorganisms, commonly referred to as the microbiota. There's a growing recognition that these gut microbes are intrinsically intertwined with mammalian physiology. Through the circulation of metabolites, they establish metabolic symbiosis, enhance immune function, and establish communication with different remote cells, including those in the brain. The gut microbiome plays a crucial part in influencing the development and performance of microglia, as indicated by recent preclinical studies. Dysbiosis of the intestinal flora leads to alterations in the microglia transcriptome that regulate the interconversion of microglia subtypes. This conversation explores recent research that clarifies how gut bacteria, their byproducts, and harmful elements affect the activation and characteristics of microglia. This understanding opens doors to innovative microbial-based therapeutic strategies for early identification and treatment goals in AD.

Keywords: Alzheimer’s disease; brain-gut axis; gastrointestinal microbiome; microglia; neurogenic inflammation.

Publication types

  • Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This project was supported by grants from the National Natural Science Foundation of Zhejiang Province (Grant No. LY20H270001 to ZW), Medicaland Health Science and Technology Project of Zhejiang Province (Grant No. 2021RC148 to ZW) and the priority research and development project of Lishui Science and Technology Bureau (Grant No. 2022ZDYF21 to ZW).