Bacteroides fragilis Lipopolysaccharide and Inflammatory Signaling in Alzheimer's Disease.
Bacteroides fragilis Lipopolysaccharide and Inflammatory Signaling in Alzheimer's Disease.
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DOI：
10.3389/fmicb.2016.01544
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发表时间：
2016
影响因子：
5.2
通讯作者：
Lukiw WJ
中科院分区：
文献类型：
--
作者：
Lukiw WJ
人类微生物组由~3.8 × 1013种共生微生物组成，形成了一个高度复杂和动态的生态系统：胃肠道构成了迄今为止最大的人类微生物组储存库，其对人类神经健康和疾病的影响越来越受到重视。拟杆菌门是胃肠道微生物组中最大的革兰氏阴性菌门，当被限制在胃肠道时通常对宿主有益，但有可能分泌一系列非常复杂的促炎神经毒素，包括表面脂多糖（lps）和有毒的蛋白水解肽。随着年龄和疾病的增长，胃肠道和血脑屏障的通透性改变或增加，这些细菌渗出物的有害作用似乎变得更加重要。例如，血清中丰富的拟杆菌属脆弱拟杆菌（Bacteroides fragilis, BF-LPS）的独特lps的存在是导致全身性炎症的主要因素。BF-LPS被TLR2、TLR4和/或CD14小胶质细胞受体进一步识别为促炎42氨基酸淀粉样蛋白- β (a - β42)肽，是阿尔茨海默病（AD）大脑的特征。在这里，我们提供了第一个证据，证明BF-LPS暴露于人类原代脑细胞是一种异常有效的促炎转录因子NF-kB （p50/p65）复合物的诱导剂，这是一种已知的触发炎症性神经变性相关致病途径表达的触发器。此外，“观点交流”还将重点介绍最近的研究工作，这些研究提出了微生物组产生的因素（如BF-LPS）在驱动AD大脑中促炎退行性神经病理方面的潜在贡献的新概念。
The human microbiome consists of ~3.8 × 1013 symbiotic microorganisms that form a highly complex and dynamic ecosystem: the gastrointestinal (GI) tract constitutes the largest repository of the human microbiome by far, and its impact on human neurological health and disease is becoming increasingly appreciated. Bacteroidetes, the largest phylum of Gram-negative bacteria in the GI tract microbiome, while generally beneficial to the host when confined to the GI tract, have potential to secrete a remarkably complex array of pro-inflammatory neurotoxins that include surface lipopolysaccharides (LPSs) and toxic proteolytic peptides. The deleterious effects of these bacterial exudates appear to become more important as GI tract and blood-brain barriers alter or increase their permeability with aging and disease. For example, presence of the unique LPSs of the abundant Bacteroidetes species Bacteroides fragilis (BF-LPS) in the serum represents a major contributing factor to systemic inflammation. BF-LPS is further recognized by TLR2, TLR4, and/or CD14 microglial cell receptors as are the pro-inflammatory 42 amino acid amyloid-beta (Aβ42) peptides that characterize Alzheimer’s disease (AD) brain. Here we provide the first evidence that BF-LPS exposure to human primary brain cells is an exceptionally potent inducer of the pro-inflammatory transcription factor NF-kB (p50/p65) complex, a known trigger in the expression of pathogenic pathways involved in inflammatory neurodegeneration. This ‘Perspectives communication’ will in addition highlight work from recent studies that advance novel and emerging concepts on the potential contribution of microbiome-generated factors, such as BF-LPS, in driving pro-inflammatory degenerative neuropathology in the AD brain.
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影响因子：
5.9
作者：
Hakansson A;Molin G
通讯作者：
Molin G
DOI：
10.2174/1874285801610010057
发表时间：
2016-01-01
期刊：
The open microbiology journal
影响因子：
--
作者：
Fathi, Payam;Wu, Shaoguang
通讯作者：
Wu, Shaoguang
影响因子：
5.5
作者：
Lin, Chuan-Sheng;Chang, Chih-Jung;Lai, Hsin-Chih
通讯作者：
Lai, Hsin-Chih
影响因子：
12.3
作者：
Bourgeois S;Jorgensen A;Zhang EJ;Hanson A;Gillman MS;Bumpstead S;Toh CH;Williamson P;Daly AK;Kamali F;Deloukas P;Pirmohamed M
通讯作者：
Pirmohamed M
影响因子：
2.1
作者：
EIDHIN, DN;MOUTON, C
通讯作者：
MOUTON, C