Zhang Guifeng, Dou Yanjie, Xie Huiwen, Pu Dan, Wang Longxing, Wang Renjun, Han Xiaofei
Key Laboratory of Saccharide and Lipid Metabolism Research in Liaoning Province, College of Life and Health of Dalian University, Dalian 116622, China.
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
Nutrients. 2025 Jul 14;17(14):2312. doi: 10.3390/nu17142312.
Oligopeptides from sea cucumber eggs (SCEPs) are rarely studied for their neuroprotective effects.
Therefore, we prepared SCEPs via simulated gastrointestinal digestion and then administered them to an Alzheimer's disease (AD) mouse model via gavage. Behavior tests, gut-brain histopathology and fecal microbiota transplantation (FMT) experiments were conducted, and gut microbiota and metabolite short-chain fatty acids (SCFAs) were evaluated via 16sRNA gene sequencing and LC-MS.
The results showed that both the SCEP and FMT groups experienced improvements in the cognitive impairments of AD and showed reduced levels of Aβ, P-Tau, GFAP, and NFL in the brain, especially in the hippocampus. SCEP remodeled the gut microbiota, increasing the relative abundances of and by 2.7- and 4.8-fold compared with the model at the genus level. In the SCEP and FMT treatments, four SCFA-producing bacteria obtained from gut microbiota profiling showed consistent trends, indicating that they may be involved in mediating the neuroprotective effects of SCEP. Mechanically, SCEP regulated the SCFA distribution in feces, blood, and the brain, greatly increased the content of SCFAs in the brain up to 2000 μg/mg, eased gut-brain barrier dysfunction, inhibited HDAC3 overexpression, and upregulated BDNF/NT3 levels.
This study provides a promising candidate for preventing AD and a reference for applying SCEP.
海参卵寡肽（SCEPs）的神经保护作用鲜有研究。
因此，我们通过模拟胃肠消化制备了SCEPs，然后通过灌胃将其给予阿尔茨海默病（AD）小鼠模型。进行了行为测试、肠脑组织病理学和粪便微生物群移植（FMT）实验，并通过16sRNA基因测序和液相色谱-质谱联用技术评估了肠道微生物群和代谢物短链脂肪酸（SCFAs）。
结果表明，SCEP组和FMT组的AD认知障碍均有改善，且大脑中Aβ、P-Tau、GFAP和NFL水平降低，尤其是在海马体中。SCEP重塑了肠道微生物群，在属水平上，与模型相比， 和 的相对丰度分别增加了2.7倍和4.8倍。在SCEP和FMT处理中，从肠道微生物群分析中获得的四种产生SCFA的细菌呈现出一致的趋势，表明它们可能参与介导SCEP的神经保护作用。从机制上讲，SCEP调节了粪便、血液和大脑中的SCFA分布，使大脑中SCFAs的含量大幅增加至2000μg/mg，缓解了肠脑屏障功能障碍，抑制了HDAC3的过表达，并上调了BDNF/NT3水平。
本研究为预防AD提供了一个有前景的候选物，并为SCEP的应用提供了参考。
