PDF(Pubmed)
Abstract：
The gut microbiota and microglia play critical roles in Alzheimer\'s disease (AD), and elevated Bacteroides is correlated with cerebrospinal fluid amyloid-β (Aβ) and tau levels in AD. We hypothesize that Bacteroides contributes to AD by modulating microglia. Here we show that administering Bacteroides fragilis to APP/PS1-21 mice increases Aβ plaques in females, modulates cortical amyloid processing gene expression, and down regulates phagocytosis and protein degradation microglial gene expression. We further show that administering Bacteroides fragilis to aged wild-type male and female mice suppresses microglial uptake of Aβ1-42 injected into the hippocampus. Depleting murine Bacteroidota with metronidazole decreases amyloid load in aged 5xFAD mice, and activates microglial pathways related to phagocytosis, cytokine signaling, and lysosomal degradation. Taken together, our study demonstrates that members of the Bacteroidota phylum contribute to AD pathogenesis by suppressing microglia phagocytic function, which leads to impaired Aβ clearance and accumulation of amyloid plaques.
摘要：
肠道菌群和小胶质细胞在阿尔茨海默病(AD)中发挥关键作用，拟杆菌升高与AD患者脑脊液β淀粉样蛋白（Aβ）和tau水平相关。我们假设拟杆菌通过调节小胶质细胞有助于AD。在这里，我们表明，对APP/PS1-21小鼠施用脆弱拟杆菌会增加雌性小鼠的Aβ斑块，调节皮质淀粉样蛋白加工基因表达，并下调吞噬和蛋白质降解小胶质细胞基因表达。我们进一步表明，对老年野生型雄性和雌性小鼠施用脆弱拟杆菌会抑制注射到海马中的Aβ1-42的小胶质细胞摄取。甲硝唑消耗小鼠类杆菌减少了5xFAD小鼠的淀粉样蛋白负荷，并激活与吞噬作用相关的小胶质细胞通路，细胞因子信号，和溶酶体降解。一起来看,我们的研究表明，类杆菌门的成员通过抑制小胶质细胞的吞噬功能来促进AD的发病，这导致受损的Aβ清除和淀粉样斑块的积累。
