Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly
Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly
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DOI：
10.1016/j.neurobiolaging.2016.08.019
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发表时间：
2017-01-01
影响因子：
4.2
通讯作者：
Frisoni, Giovanni B.
中科院分区：
文献类型：
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作者：
Cattaneo, Annamaria;Cattane, Nadia;Frisoni, Giovanni B.
从淀粉样蛋白-b沉积到认知障碍的途径被认为是阿尔茨海默病（AD）发病机制的基石。然而，在散发的非遗传性AD病例中，是什么驱动淀粉样蛋白积聚仍然是未知的。AD大脑的特征是淀粉样斑块周围的炎症反应，肠道微生物群（GMB）的特定子集可能会促进大脑炎症。我们通过研究脑淀粉样变性与（1）具有促炎和抗炎活性的GMB分类群和（2）认知受损患者外周炎症的相关性，研究了GMB在AD发病机制中的可能作用。我们测量了选定的细菌GMB分类群的粪便丰度（埃希氏菌/志贺氏菌、铜绿假单胞菌、直肠真杆菌、霍氏真杆菌、普氏粪杆菌和脆弱拟杆菌）和细胞因子的血液表达水平（促炎细胞因子：CXCL 2、CXCL 10、白细胞介素[IL]-1 β、IL-6、IL-18、IL-8、炎性小体复合物（NLRP 3）、肿瘤坏死因子-α [TNF-α];抗炎细胞因子：IL-4、IL-10、IL-13）在患有脑淀粉样变性的认知受损患者（n = 40，Amy+）和没有脑淀粉样变性的认知受损患者（n = 33，Amy-）以及对照组（n = 10，没有脑淀粉样变性和没有认知受损）中的作用。与对照组和Amy-患者相比，Amy+患者显示出更高水平的促炎细胞因子（IL-6、CXCL 2、NLRP 3和IL-1 β）。在Amy+与Amy-中观察到抗炎细胞因子IL-10的减少。Amy+的E丰度较低。与健康对照（倍数变化，分别为FC =-9.6，p < 0.001和FC =+12.8，p <0.001）和Amy-（FC =-7.7，p < 0.001和FC =+7.4，p = 0.003）相比，大肠杆菌/志贺氏菌的直肠和更高丰度。观察到促炎细胞因子IL-1b、NLRP 3和CXCL 2与炎性细菌分类群埃希氏菌/志贺氏菌的丰度呈正相关（分别为rho = 0.60，p <0.001; rho = 0.57，p < 0.001; rho = 0.30，p = 0.007），与抗炎性大肠杆菌呈负相关。直肠（rho =-0.48，p < 0.001; rho =-0.25，p = 0.024; rho =-0.49，p < 0.001）。我们的数据表明，促炎GMB分类群Escherichia/Shigella丰度的增加和抗炎分类群E.直肠，可能与认知障碍和脑淀粉样变性患者的外周炎症状态有关。GMB相关炎症和淀粉样变性之间的可能因果关系值得进一步研究。(C)2016 Elsevier Inc. All rights reserved.
The pathway leading from amyloid-b deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer's disease (AD). However, what drives amyloid buildup in sporadic nongenetic cases of AD is still unknown. AD brains feature an inflammatory reaction around amyloid plaques, and a specific subset of the gut microbiota (GMB) may promote brain inflammation. We investigated the possible role of the GMB in AD pathogenesis by studying the association of brain amyloidosis with (1) GMB taxa with pro-and anti-inflammatory activity; and (2) peripheral inflammation in cognitively impaired patients. We measured the stool abundance of selected bacterial GMB taxa (Escherichia/Shigella, Pseudomonas aeruginosa, Eubacterium rectale, Eubacterium hallii, Faecalibacterium prausnitzii, and Bacteroides fragilis) and the blood expression levels of cytokines (pro-inflammatory cytokines: CXCL2, CXCL10, interleukin [IL]-1 beta, IL-6, IL-18, IL-8, inflammasome complex (NLRP3), tumor necrosis factor-alpha [TNF-alpha]; anti-inflammatory cytokines: IL-4, IL-10, IL-13) in cognitively impaired patients with (n = 40, Amy+) and with no brain amyloidosis (n = 33, Amy-) and also in a group of controls (n = 10, no brain amyloidosis and no cognitive impairment). Amy+ patients showed higher levels of pro-inflammatory cytokines (IL-6, CXCL2, NLRP3, and IL-1 beta) compared with both controls and with Amy- patients. A reduction of the anti-inflammatory cytokine IL-10 was observed in Amy+ versus Amy-. Amy+ showed lower abundance of E. rectale and higher abundance of Escherichia/Shigella compared with both healthy controls (fold change, FC = - 9.6, p < 0.001 and FC = +12.8, p < 0.001, respectively) and to Amy- (FC = - 7.7, p < 0.001 and FC = +7.4, p = 0.003). A positive correlation was observed between pro-inflammatory cytokines IL-1b, NLRP3, and CXCL2 with abundance of the inflammatory bacteria taxon Escherichia/Shigella (rho = 0.60, p < 0.001; rho = 0.57, p < 0.001; and rho = 0.30, p = 0.007, respectively) and a negative correlation with the anti-inflammatory E. rectale (rho = - 0.48, p < 0.001; rho = - 0.25, p = 0.024; rho = - 0.49, p < 0.001). Our data indicate that an increase in the abundance of a pro-inflammatory GMB taxon, Escherichia/Shigella, and a reduction in the abundance of an anti-inflammatory taxon, E. rectale, are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. A possible causal relation between GMB-related inflammation and amyloidosis deserves further investigation. (C) 2016 Elsevier Inc. All rights reserved.