Target Dysbiosis of Gut Microbes as a Future Therapeutic Manipulation in Alzheimer's Disease.

Feiqi Zhu,Fengna Chu,Xiaoping Tian,Chunrong Li,Jie Zhu

doi:10.3389/fnagi.2020.544235

Abstract

Alzheimer’s disease (AD) is commonly an age-associated dementia with neurodegeneration. The pathogenesis of AD is complex and still remains unclear. The inflammation, amyloid β (Aβ), and neurofibrillary tangles as well misfolded tau protein in the brain may contribute to the occurrence and development of AD. Compared with tau protein, Aβ is less toxic. So far, all efforts made in the treatments of AD with targeting these pathogenic factors were unsuccessful over the past decades. Recently, many studies demonstrated that changes of the intestinal environment and gut microbiota via gut–brain axis pathway can cause neurological disorders, such as AD, which may be involved in the pathogenesis of AD. Thus, remodeling the gut microbiota by various ways to maintain their balance might be a novel therapeutic strategy for AD. In the review article, we analyzed the characteristics of gut microbiota and its dysbiosis in AD and its animal models and investigated the possibility of targeting the gut microbiota in the treatment of the patients with AD in the future.

Highlights

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disorder and the most common form of age-associated dementia
We considered that the infections by H. pylori and B. burgdorferi and enhanced Bacteroides may promote amyloid β (Aβ) deposition or tau accumulation in the gut of AD patients, which needed to be evidenced in the future studies
The gut microbiome may contribute to the pathogenesis of AD and neurodegenerative disorders through the microbiota–gut–brain axis pathway

Summary

INTRODUCTION

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disorder and the most common form of age-associated dementia. Enhanced genus Clostridium and declined Bacteroides as the feature of the gut dysbiosis were caused by high corticosterone levels in the stressed mice (Bailey et al, 2011) The glucocorticoids have both proinflammatory and anti-inflammatory roles; inflammations are related to damaged HPA axis functionality in AD and other neurodegenerative disorders (Silverman and Sternberg, 2012; Bellavance and Rivest, 2014; Hueston and Deak, 2014). The gut dysbiosis could lead to dysfunctions of both innate and adoptive immune through several ways, such as changing antigen presentations, cytokines production, and lymphocyte functions, as well as increasing inflammation, etc., can cause the gut–brain axis malfunction (Levy et al, 2017).

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CONCLUSIONS

Results