Jia Mengzhen, Wang Xiaorui, Ning Fangjie, Wang Wenxiu, Hu Xinyu, Geng Kexin, Wen Junqing, Wu Shan, Wang Bin, Liu Zhigang
College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China.
School of Food and Bioengineering, Zhengzhou University of Light Industry, Zhengzhou 450001, China.
Food Funct. 2025 Jul 1;16(13):5345-5362. doi: 10.1039/d4fo06272h.
Alzheimer's disease (AD) is mainly manifested by cognitive dysfunction, accompanied by excessive β-amyloid (Aβ) deposition and neuroinflammation. The regulation of vagus nerve (VN) signal transmission is crucial for influencing the pathological progression of AD and exploring new therapeutic approaches. Two doses of 2'-fucosyllactose (2'-FL, 500 and 1000 mg kg) were administered orally to AD model mice. 2'-FL rescued spatial and recognition memory deficits in AD mice. Moreover, 2'-FL reduced Aβ deposition and neuroinflammation. 2'-FL enhances c-Fos expression in the solitary tract nucleus (NTS). This suggested that 2'-FL alleviated AD-related cognition by enhancing VN afferent activity. Vagotomy demonstrated that the alleviation of AD-related cognition by 2'-FL depended on the presence of VN. Moreover, 2'-FL enhanced gut barrier function and alleviated gut inflammation. Notably, 2'-FL also reshaped the gut microbiota composition, increasing the relative abundance of , , and others. Moreover, 2'-FL promoted the production of short-chain fatty acids (SCFAs). Correlation analysis showed that propionate was highly correlated with other related indicators. After vagotomy, although 2'-FL promoted SCFA production, it did not alleviate cognitive impairment. This suggested that the neuroprotective effect of SCFAs could also be partially dependent on the VN. 2'-FL rescued the cognitive deficits in AD mice, which was partly explained by changes in gut microbial composition, production of SCFAs, and the presence of VN.
阿尔茨海默病（AD）主要表现为认知功能障碍，伴有过量的β-淀粉样蛋白（Aβ）沉积和神经炎症。迷走神经（VN）信号传递的调节对于影响AD的病理进展和探索新的治疗方法至关重要。给AD模型小鼠口服两剂2'-岩藻糖基乳糖（2'-FL，500和1000 mg/kg）。2'-FL改善了AD小鼠的空间和识别记忆缺陷。此外，2'-FL减少了Aβ沉积和神经炎症。2'-FL增强了孤束核（NTS）中的c-Fos表达。这表明2'-FL通过增强VN传入活动减轻了与AD相关的认知。迷走神经切断术表明，2'-FL对AD相关认知的减轻依赖于VN的存在。此外，2'-FL增强了肠道屏障功能并减轻了肠道炎症。值得注意的是，2'-FL还重塑了肠道微生物群组成，增加了 、 等的相对丰度。此外，2'-FL促进了短链脂肪酸（SCFAs）的产生。相关性分析表明，丙酸与其他相关指标高度相关。迷走神经切断术后，虽然2'-FL促进了SCFA的产生，但并未减轻认知障碍。这表明SCFAs的神经保护作用也可能部分依赖于VN。2'-FL改善了AD小鼠的认知缺陷，这部分可以通过肠道微生物组成的变化、SCFAs的产生以及VN的存在来解释。
