Department of Rehabilitation Medicine, Xuan Wu Hospital, Capital Medical University, 45 Chang Chun Street, Beijing, 100053, China.
Peking University China-Japan Friendship School of Clinical Medicine, Beijing, 100029, China.
Eur J Nutr. 2023 Oct;62(7):2991-3007. doi: 10.1007/s00394-023-03208-7. Epub 2023 Jul 17.
Prebiotics, including fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS), stimulate beneficial gut bacteria and may be helpful for patients with Alzheimer's disease (AD). This study aimed to compare the effects of FOS and GOS, alone or in combination, on AD mice and to identify their underlying mechanisms.
Six-month-old APP/PS1 mice and wild-type mice were orally administered FOS, GOS, FOS + GOS or water by gavage for 6 weeks and then subjected to relative assays, including behavioral tests, biochemical assays and 16S rRNA sequencing.
Through behavioral tests, we found that GOS had the best effect on reversing cognitive impairment in APP/PS1 mice, followed by FOS + GOS, while FOS had no effect. Through biochemical techniques, we found that GOS and FOS + GOS had effects on multiple targets, including diminishing Aβ burden and proinflammatory IL-1β and IL-6 levels, and changing the concentrations of neurotransmitters GABA and 5-HT in the brain. In contrast, FOS had only a slight anti-inflammatory effect. Moreover, through 16S rRNA sequencing, we found that prebiotics changed composition of gut microbiota. Notably, GOS increased relative abundance of Lactobacillus, FOS increased that of Bifidobacterium, and FOS + GOS increased that of both. Furthermore, prebiotics downregulated the expression levels of proteins of the TLR4-Myd88-NF-κB pathway in the colons and cortexes, suggesting the involvement of gut-brain mechanism in alleviating neuroinflammation.
Among the three prebiotics, GOS was the optimal one to alleviate cognitive impairment in APP/PS1 mice and the mechanism was attributed to its multi-target role in alleviating Aβ pathology and neuroinflammation, changing neurotransmitter concentrations, and modulating gut microbiota.
包括低聚果糖（FOS）和低聚半乳糖（GOS）在内的益生元可刺激有益的肠道细菌，对阿尔茨海默病（AD）患者可能有帮助。本研究旨在比较 FOS 和 GOS 单独或联合应用于 AD 小鼠的效果，并确定其潜在机制。
将 6 个月大的 APP/PS1 小鼠和野生型小鼠通过灌胃给予 FOS、GOS、FOS+GOS 或水，持续 6 周，然后进行相对检测，包括行为测试、生化检测和 16S rRNA 测序。
通过行为测试，我们发现 GOS 对逆转 APP/PS1 小鼠认知障碍的效果最好，其次是 FOS+GOS，而 FOS 则没有效果。通过生化技术，我们发现 GOS 和 FOS+GOS 对多个靶点有作用，包括减轻 Aβ 负担和促炎细胞因子 IL-1β 和 IL-6 水平，并改变大脑中神经递质 GABA 和 5-HT 的浓度。相比之下，FOS 仅有轻微的抗炎作用。此外，通过 16S rRNA 测序，我们发现益生元改变了肠道微生物群的组成。值得注意的是，GOS 增加了乳酸菌的相对丰度，FOS 增加了双歧杆菌的相对丰度，而 FOS+GOS 则增加了两者的相对丰度。此外，益生元下调了结肠和皮质中 TLR4-Myd88-NF-κB 通路蛋白的表达水平，提示肠道-大脑机制参与了缓解神经炎症。
在这三种益生元中，GOS 是缓解 APP/PS1 小鼠认知障碍的最佳选择，其机制归因于其在缓解 Aβ 病理学和神经炎症、改变神经递质浓度以及调节肠道微生物群方面的多靶点作用。
