Gut Microbiota Composition and Epigenetic Molecular Changes Connected to the Pathogenesis of Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder, and its pathogenesis is not fully known. Although there are several hypotheses, such as neuroinflammation, tau hyperphosphorylation, amyloid-β plaques, neurofibrillary tangles, and oxidative stress, none of them completely explain the origin and progression of AD. Emerging evidence suggests that gut microbiota and epigenetics can directly influence the pathogenesis of AD via their effects on multiple pathways, including neuroinflammation, oxidative stress, and amyloid protein. Various gut microbes such as Actinobacteria, Bacteroidetes, E. coli, Firmicutes, Proteobacteria, Tenericutes, and Verrucomicrobia are known to play a crucial role in the pathogenesis of AD. These microbes and their metabolites modulate various physiological processes that contribute to AD pathogenesis, such as neuroinflammation and other inflammatory processes, amyloid deposition, cytokine storm syndrome, altered BDNF and NMDA signaling, impairing neurodevelopmental processes. Likewise, epigenetic markers associated with AD mainly include histone modifications and DNA methylation, which are under the direct control of a variety of enzymes, such as acetylases and methylases. The activity of these enzymes is dependent upon the metabolites generated by the host's gut microbiome, suggesting the significance of epigenetics in AD pathogenesis. It is interesting to know that both gut microbiota and epigenetics are dynamic processes and show a high degree of variation according to diet, stressors, and environmental factors. The bidirectional relation between the gut microbiota and epigenetics suggests that they might work in synchrony to modulate AD representation, its pathogenesis, and progression. They both also provide numerous targets for early diagnostic biomarkers and for the development of AD therapeutics. This review discusses the gut microbiota and epigenetics connection in the pathogenesis of AD and aims to highlight vast opportunities for diagnosis and therapeutics of AD.

Keywords: Alzheimer’s disease; CNS complications; Epigenetics; Gut microbiota; Gut–brain axis; Pathophysiology of Alzheimer’s disease.