Navalpur Shanmugam Nanda K, Zamudio Frank, Vijaya Kumar Deepak K, Barrett Kianna A, VanDoren Ryan, Chen Meng, Barr Olivia M, Watson Sara, Lin Chih-Chung Jerry, Eimer William A, Jorfi Mehdi, Choi Se Hoon, Moir Robert D, Tanzi Rudolph E
Genetics and Aging Research Unit, Henry and Allison McCance Center for Brain Health, Department of Neurology, Massachusetts General Hospital, and Harvard Medical School, Charlestown, Massachusetts, USA.
Alzheimers Dement. 2025 Jun;21(6):e70292. doi: 10.1002/alz.70292.
Emerging evidence has connected Alzheimer's disease (AD) to systemic inflammation, intestinal abnormalities, and altered gut microbiota, highlighting the significance of the gut-brain axis. Here, we investigated the impact of acute experimental colitis (acute colitis) on AD pathology.
Acute colitis was induced in 2-month-old 5xFAD mice using dextran sodium sulfate (DSS) to assess the effects of intestinal inflammation on the microbiome, systemic inflammation, neuroinflammation, and beta-amyloid deposition.
Induction of acute colitis in 5xFAD mice led to microbial dysbiosis and systemic inflammation. As a result, monocyte infiltration was observed in the brain accompanied by reduced cerebral beta-amyloid deposition and increased beta-amyloid efflux into the bloodstream.
Increased infiltration of monocytes and elevated beta-amyloid release into the bloodstream could both be responsible for the reduced beta-amyloid deposition in 5xFAD mice following acute colitis. These results further highlight an important connection between gut-induced peripheral inflammation and the progression of AD.
Microbial dysbiosis occurs as a result of acute colitis in 5xFAD mice. Acute colitis in 5xFAD mice affects beta-amyloid deposition. Increased IL-2 and IL-6 cytokine levels in the hippocampus of 5xFAD colitis mice. Colitis in 5xFAD mice increases serum proinflammatory cytokine levels and endotoxins. Acute colitis in 5xFAD mice increases monocyte infiltration and serum beta-amyloid.
新出现的证据将阿尔茨海默病（AD）与全身炎症、肠道异常及肠道微生物群改变联系起来，凸显了肠脑轴的重要性。在此，我们研究了急性实验性结肠炎（急性结肠炎）对AD病理的影响。
使用葡聚糖硫酸钠（DSS）在2月龄的5xFAD小鼠中诱导急性结肠炎，以评估肠道炎症对微生物群、全身炎症、神经炎症和β-淀粉样蛋白沉积的影响。
在5xFAD小鼠中诱导急性结肠炎导致微生物失调和全身炎症。结果，在大脑中观察到单核细胞浸润，同时脑内β-淀粉样蛋白沉积减少，且β-淀粉样蛋白向血液中的流出增加。
单核细胞浸润增加和β-淀粉样蛋白向血液中释放增加都可能是急性结肠炎后5xFAD小鼠β-淀粉样蛋白沉积减少的原因。这些结果进一步凸显了肠道诱导的外周炎症与AD进展之间的重要联系。
5xFAD小鼠急性结肠炎导致微生物失调。5xFAD小鼠急性结肠炎影响β-淀粉样蛋白沉积。5xFAD结肠炎小鼠海马中白细胞介素-2和白细胞介素-6细胞因子水平升高。5xFAD小鼠的结肠炎增加血清促炎细胞因子水平和内毒素。5xFAD小鼠急性结肠炎增加单核细胞浸润和血清β-淀粉样蛋白。
