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揭示厌氧菌小生境与阿尔茨海默病发病机制之间的复杂联系。

Unveiling the Intricate Link Between Anaerobe Niche and Alzheimer Disease Pathogenesis.

机构信息

Department of Pathology and Laboratory Medicine, Medical University of South Carolina.

Department of Biology, College of Charleston.

出版信息

J Infect Dis. 2024 Sep 10;230(Supplement_2):S117-S127. doi: 10.1093/infdis/jiae312.

DOI:10.1093/infdis/jiae312
PMID:39255391
Abstract

Dysbiosis within microbiomes has been increasingly implicated in many systemic illnesses, such as cardiovascular disease, metabolic syndrome, respiratory infections, and Alzheimer disease (Ad). The correlation between Ad and microbial dysbiosis has been repeatedly shown, yet the etiologic cause of microbial dysbiosis remains elusive. From a neuropathology perspective, abnormal (often age-related) changes in the brain, associated structures, and bodily lumens tend toward an accumulation of oxygen-depleted pathologic structures, which are anaerobically selective niches. These anaerobic environments may promote progressive change in the microbial community proximal to the brain and thus deserve further investigation. In this review, we identify and explore what is known about the anaerobic niche near or associated with the brain and the anaerobes that it is harbors. We identify the anaerobe stakeholders within microbiome communities and the impacts on the neurodegenerative processes associated with Ad. Chronic oral dysbiosis in anaerobic dental pockets and the composition of the gut microbiota from fecal stool are the 2 largest anaerobic niche sources of bacterial transference to the brain. At the blood-brain barrier, cerebral atherosclerotic plaques are predominated by anaerobic species intimately associated with the brain vasculature. Focal cerebritis/brain abscess and corpora amylacea may also establish chronic anaerobic niches in direct proximity to brain parenchyma. In exploring the anaerobic niche proximal to the brain, we identify research opportunities to explore potential sources of microbial dysbiosis associated with Ad.

摘要

肠道菌群失调与许多系统性疾病有关,如心血管疾病、代谢综合征、呼吸道感染和阿尔茨海默病(AD)。AD 与微生物失调之间的相关性已经反复得到证实,但微生物失调的病因仍然难以捉摸。从神经病理学的角度来看,大脑、相关结构和体腔的异常(通常与年龄相关)变化往往导致缺氧的病理结构堆积,这些结构是厌氧选择性小生境。这些厌氧环境可能会促进大脑附近微生物群落的渐进性变化,因此值得进一步研究。在这篇综述中,我们确定并探讨了与大脑附近或相关的厌氧小生境以及其中所包含的厌氧菌。我们确定了微生物群落中厌氧生物的利益相关者及其对 AD 相关神经退行性过程的影响。慢性口腔厌氧性牙周袋失调和粪便中肠道微生物群的组成是细菌向大脑转移的 2 个最大的厌氧小生境来源。在血脑屏障中,大脑动脉粥样硬化斑块主要由与大脑血管密切相关的厌氧物种组成。局灶性脑(节)炎/脑脓肿和脑淀粉样体也可能在大脑实质附近建立慢性厌氧小生境。在探索大脑附近的厌氧小生境时,我们确定了研究机会,以探索与 AD 相关的微生物失调的潜在来源。

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