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.

阿尔茨海默病（AD）是一种神经退行性疾病，其发病机制尚不完全清楚。尽管有多种假设，如神经炎症、tau 过度磷酸化、β 淀粉样蛋白斑块、神经原纤维缠结和氧化应激，但没有一个可以完全解释 AD 的起源和进展。新出现的证据表明，肠道微生物群和表观遗传学可以通过对多种途径的影响直接影响 AD 的发病机制，包括神经炎症、氧化应激和淀粉样蛋白。各种肠道微生物，如放线菌门、拟杆菌门、大肠杆菌、厚壁菌门、变形菌门、Tenericutes和Verrucomicrobia已知在 AD 的发病机制中起关键作用。这些微生物及其代谢物调节导致 AD 发病机制的各种生理过程，例如神经炎症和其他炎症过程、淀粉样蛋白沉积、细胞因子风暴综合征、改变的 BDNF 和 NMDA 信号传导、损害神经发育过程。同样，与 AD 相关的表观遗传标记主要包括组蛋白修饰和 DNA 甲基化，它们受多种酶的直接控制，例如乙酰化酶和甲基化酶。这些酶的活性取决于宿主肠道微生物组产生的代谢物，这表明表观遗传学在 AD 发病机制中的重要性。有趣的是，肠道微生物群和表观遗传学都是动态过程，并且会根据饮食、压力源和环境因素表现出高度的变化。肠道微生物群和表观遗传学之间的双向关系表明它们可能同步调节 AD 表现、发病机制和进展。它们还为早期诊断生物标志物和开发 AD 疗法提供了许多目标。本综述讨论了 AD 发病机制中肠道微生物群和表观遗传学的联系，旨在突出 AD 诊断和治疗的巨大机会。和进步。它们还为早期诊断生物标志物和开发 AD 疗法提供了许多目标。本综述讨论了 AD 发病机制中肠道微生物群和表观遗传学的联系，旨在突出 AD 诊断和治疗的巨大机会。和进步。它们还为早期诊断生物标志物和开发 AD 疗法提供了许多目标。本综述讨论了 AD 发病机制中肠道微生物群和表观遗传学的联系，旨在突出 AD 诊断和治疗的巨大机会。