Harding Alice, Robinson Sarita, Crean StJohn, Singhrao Sim K
J Alzheimers Dis. 2017;58(2):337-348. doi: 10.3233/JAD-170046.
A risk factor relationship exists between periodontal disease and Alzheimer's disease (AD) via tooth loss, and improved memory following dental intervention. This links the microbial contribution from indigenous oral periodontal pathogens to the manifestation of chronic conditions, such as AD. Here, we use Porphyromonas gingivalis infection to illustrate its effect on mental health. P. gingivalis infection, in its primary sub-gingival niche, can cause polymicrobial synergy and dysbiosis. Dysbiosis describes the residency of select commensals from the oral cavity following co-aggregation around the dominant keystone pathogen, such as P. gingivalis, to gain greater virulence. The initial process involves P. gingivalis disturbing neutrophil mediated innate immune responses in the healthy gingivae and then downregulating adaptive immune cell differentiation and development to invade, and subsequently, establish new dysbiotic bacterial communities. Immune responses affect the host in general and functionally via dietary adjustments caused by tooth loss. Studies from animals orally infected with P. gingivalis confirm this bacterium can transmigrate to distant organ sites (the brain) and contribute toward peripheral and intracerebral inflammation, and compromise vascular and microvascular integrity. In another study, P. gingivalis infection caused sleep pattern disturbances by altering glial cell light/dark molecular clock activity, and this, in turn, can affect the clearance of danger associated molecular patterns, such as amyloid-β, via the glymphatic system. Since P. gingivalis can transmigrate to the brain and modulate organ-specific inflammatory innate and adaptive immune responses, this paper explores whether better management of indigenous periodontal bacteria could delay/prevent the onset and/or progression of dementia.
通过牙齿缺失，牙周病与阿尔茨海默病（AD）之间存在风险因素关系，并且牙科干预后记忆力得到改善。这将口腔内源性牙周病原体的微生物作用与慢性疾病（如AD）的表现联系起来。在此，我们使用牙龈卟啉单胞菌感染来说明其对心理健康的影响。牙龈卟啉单胞菌感染在其主要的龈下生态位中可导致多种微生物协同作用和生态失调。生态失调描述了在优势关键病原体（如牙龈卟啉单胞菌）周围共同聚集后，口腔中特定共生菌的定植，以获得更大的毒力。初始过程涉及牙龈卟啉单胞菌干扰健康牙龈中中性粒细胞介导的固有免疫反应，然后下调适应性免疫细胞的分化和发育，以便侵入并随后建立新的生态失调细菌群落。免疫反应通常通过牙齿缺失引起的饮食调整在功能上影响宿主。对口服感染牙龈卟啉单胞菌的动物的研究证实，这种细菌可迁移至远处器官部位（大脑），并导致外周和脑内炎症，损害血管和微血管完整性。在另一项研究中，牙龈卟啉单胞菌感染通过改变神经胶质细胞的明暗分子时钟活动导致睡眠模式紊乱，进而可通过淋巴系统影响危险相关分子模式（如β淀粉样蛋白）的清除。由于牙龈卟啉单胞菌可迁移至大脑并调节器官特异性炎症固有免疫和适应性免疫反应，本文探讨了更好地管理口腔内源性牙周细菌是否可以延缓/预防痴呆症的发生和/或进展。
