Kong Wei, Lan Fei, Awan Umer Farooq, Qing Hong, Ni Junjun
Key Laboratory of Molecular Medicine and Biotherapy, School of Life Sciences, Beijing Institute of Technology, Beijing, China.
Laboratory of Molecular Biology, Department of Botany, Government College University, Lahore, Pakistan.
Front Cell Neurosci. 2021 Apr 14;15:633735. doi: 10.3389/fncel.2021.633735. eCollection 2021.
Alzheimer's disease (AD) is one of the most frequently diagnosed neurodegenerative disorders worldwide and poses a major challenge for both affected individuals and their caregivers. AD is a progressive neurological disorder associated with high rates of brain atrophy. Despite its durable influence on human health, understanding AD has been complicated by its enigmatic and multifactorial nature. Neurofibrillary tangles and the deposition of amyloid-beta (Aβ) protein are typical pathological features and fundamental causes of cognitive impairment in AD patients. Dysbiosis of oral and gut microbiota has been reported to induce and accelerate the formation of Aβ plaques and neurofibrillary tangles. For instance, some oral microbes can spread to the brain through cranial nerves or cellular infections, which has been suggested to increase the risk of developing AD. Importantly, the interaction between intestinal microbiota and brain cells has been recognized as influencing the development of AD as well as other neurodegenerative diseases. In particular, the metabolites produced by certain intestinal microorganisms can affect the activity of microglia and further mediate neuroinflammation, which is a leading cause of neuronal necrosis and AD pathogenesis. Which pathogens and associated pathways are involved in the development and progression of AD remains to be elucidated; however, it is well-known that gut microbiota and their metabolites can affect the brain by both direct and indirect means. Understanding the specific mechanisms involved in the interaction between these pathogens and the nervous system is vital for the early intervention in AD. In this review, we aim to comprehensively discuss the possible mechanistic pathways underlying the oral-brain, the gut-brain and the oral-gut-brain associations.
阿尔茨海默病（AD）是全球最常被诊断出的神经退行性疾病之一，对患者及其护理人员都构成了重大挑战。AD是一种与高脑萎缩率相关的进行性神经疾病。尽管它对人类健康有着持久影响，但由于其神秘且多因素的性质，对AD的理解一直很复杂。神经纤维缠结和β-淀粉样蛋白（Aβ）的沉积是AD患者认知障碍的典型病理特征和根本原因。据报道，口腔和肠道微生物群失调会诱导并加速Aβ斑块和神经纤维缠结的形成。例如，一些口腔微生物可通过颅神经或细胞感染扩散至大脑，这被认为会增加患AD的风险。重要的是，肠道微生物群与脑细胞之间的相互作用已被认为会影响AD以及其他神经退行性疾病的发展。特别是，某些肠道微生物产生的代谢产物可影响小胶质细胞的活性，并进一步介导神经炎症，而神经炎症是神经元坏死和AD发病机制的主要原因。哪些病原体及相关途径参与了AD的发生和发展仍有待阐明；然而，众所周知，肠道微生物群及其代谢产物可通过直接和间接方式影响大脑。了解这些病原体与神经系统之间相互作用的具体机制对于AD的早期干预至关重要。在本综述中，我们旨在全面讨论口腔-脑、肠道-脑和口腔-肠道-脑关联潜在的可能机制途径。
