Zhang Pei, Liu Yan, Jin Xin, Hu Zhaoliang, Yang Jucui, Lu Haotian, Hang Taijun, Song Min
Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, China.
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, China.
J Alzheimers Dis. 2025 Jan;103(2):487-505. doi: 10.1177/13872877241302498. Epub 2024 Dec 5.
() has been found to enter the brain and induce inflammation, contributing to Alzheimer's disease (AD). is also closely linked to gut dysbiosis. However, does induce AD-like pathology through the microbiota-gut-brain axis? There is limited literature on this topic.
To determine the precise causal link among , intestinal inflammation, and AD-related pathology.
12- to 13-month-old female C57BL/6J mice were subjected to ligature placement and oral administration of over a 24-week period. Then, cognitive performance was evaluated with behavioral tests, while AD neuropathological changes, neuroinflammation, and intestinal inflammation were assessed through qPCR, immunofluorescence, and western blot, and gut microbiota was analyzed by 16S rRNA.
Mice exposed to showed impaired behavior in open field test, novel object recognition, and Y-maze tests. The bacterium infiltrated their brains, increasing Aβ, AβPP, and Aβ fragments, promoting tau phosphorylation and microglial activation, and reducing levels of ZO-1, PSD95, SYP, and NeuN proteins. Inflammatory factors like NLRP3, caspase-1, IL-1β, IL-6, and TNF-α were elevated in both brains and intestine, while ZO-1 and occludin levels decreased in intestine. also altered gut microbial compositions.
induced gut dysbiosis and activated the NLRP3 inflammasome in the intestine and brains of mice. This led to impairment of both the intestinal and brain-blood barriers, triggering neuroinflammation and promoting the progression of AD. These findings highlight the critical role of NLRP3 inflammasome activation in the microbiota-gut-brain axis in the AD-like pathology induced by
已发现（某物质）进入大脑并引发炎症，导致阿尔茨海默病（AD）。（该物质）也与肠道菌群失调密切相关。然而，（该物质）是否通过微生物群-肠道-脑轴诱发类似AD的病理变化呢？关于这一主题的文献有限。
确定（该物质）、肠道炎症和AD相关病理之间的确切因果联系。
对12至13月龄的雌性C57BL/6J小鼠进行结扎处理，并在24周内口服（该物质）。然后，通过行为测试评估认知能力，同时通过qPCR、免疫荧光和蛋白质印迹法评估AD神经病理变化、神经炎症和肠道炎症，并通过16S rRNA分析肠道微生物群。
接触（该物质）的小鼠在旷场试验、新物体识别试验和Y迷宫试验中表现出行为受损。该细菌侵入它们的大脑，增加Aβ、AβPP和Aβ片段，促进tau磷酸化和小胶质细胞活化，并降低ZO-1、PSD95、SYP和NeuN蛋白水平。大脑和肠道中的NLRP3、caspase-1、IL-1β、IL-6和TNF-α等炎症因子升高，而肠道中ZO-1和闭合蛋白水平降低。（该物质）还改变了肠道微生物组成。
（该物质）诱发肠道菌群失调，并激活小鼠肠道和大脑中的NLRP3炎性小体。这导致肠道和脑血屏障受损，引发神经炎症并促进AD的进展。这些发现突出了NLRP3炎性小体激活在由（该物质）诱导的类似AD病理的微生物群-肠道-脑轴中的关键作用
