DataSheet_1_Porphyromonas gingivalis-Induced Cognitive Impairment Is Associated With Gut Dysbiosis, Neuroinflammation, and Glymphatic Dysfunction.zip

BackgroundPeriodontal pathogen and gut microbiota are closely associated with the pathogenesis of Alzheimer’s disease (AD). Porphyromonas gingivalis (Pg), the keystone periodontal pathogen, can induce cognitive impairment. The gut has a connection and communication with the brain, which is an important aspect of the gut–brain axis (GBA). In the present study, we investigate whether Pg induces cognitive impairment through disturbing the GBA.
MethodsIn this study, Pg was orally administered to mice, three times a week for 1 month. The effects of Pg administration on the gut and brain were evaluated through behaviors, gut microbiota, immune cells, glymphatic pathway clearance, and neuroinflammation.
ResultsPg induced cognitive impairment and dysbiosis of gut microbiota. The α-diversity parameters did not show significant change after Pg administration. The β-diversity demonstrated that the gut microbiota compositions were different between the Pg-administered and control groups. At the species level, the Pg group displayed a lower abundance of Parabacteroides gordonii and Ruminococcus callidus than the control group, but a higher abundance of Mucispirillum schaedleri. The proportions of lymphocytes in the periphery and myeloid cells infiltrating the brain were increased in Pg-treated animals. In addition, the solute clearance efficiency of the glymphatic system decreased. Neurons in the hippocampus and cortex regions were reduced in mice treated with Pg. Microglia, astrocytes, and apoptotic cells were increased. Furthermore, amyloid plaque appeared in the hippocampus and cortex regions in Pg-treated mice.
ConclusionsThese findings indicate that Pg may play an important role in gut dysbiosis, neuroinflammation, and glymphatic system impairment, which may in turn lead to cognitive impairment.

背景
牙周病原体与肠道菌群（gut microbiota）与阿尔茨海默病（Alzheimer’s disease, AD）的发病机制密切相关。牙龈卟啉单胞菌（Porphyromonas gingivalis, Pg）作为关键牙周致病菌，可诱导认知功能损伤。肠道与大脑存在连接与通讯，这是肠-脑轴（gut–brain axis, GBA）的重要内涵。本研究旨在探讨Pg是否通过扰动肠-脑轴诱导认知功能损伤。
方法
本研究通过经口给药方式向小鼠施以Pg，每周给药3次，持续1个月。通过行为学检测、肠道菌群分析、免疫细胞表征、胶质淋巴通路（glymphatic pathway）清除功能评估及神经炎症检测，分析Pg给药对肠道与大脑的影响。
结果
Pg可诱导小鼠出现认知功能损伤及肠道菌群失调（gut microbiota dysbiosis）。Pg给药后，肠道菌群的α多样性（α-diversity）参数无显著变化；β多样性（β-diversity）分析显示，Pg给药组与对照组的肠道菌群组成存在显著差异。在物种水平上，Pg组的戈登副杆菌（Parabacteroides gordonii）和卡氏瘤胃球菌（Ruminococcus callidus）丰度低于对照组，而沙氏黏螺菌（Mucispirillum schaedleri）丰度更高。Pg处理组小鼠外周淋巴细胞及浸润至大脑的髓系细胞比例均显著升高。此外，胶质淋巴系统的溶质清除效率下降。Pg处理小鼠的海马及皮层区域神经元数量减少，小胶质细胞、星形胶质细胞与凋亡细胞数量均增加。进一步观察发现，Pg处理小鼠的海马及皮层区域出现淀粉样斑块（amyloid plaque）。
结论
本研究结果表明，Pg可能在肠道菌群失调、神经炎症及胶质淋巴系统损伤中发挥重要作用，进而可能导致认知功能损伤。