Effect of Human Milk Oligosaccharides on Learning and Memory in Mice with Alzheimer’s Disease
Haina Gao, Bing Fang, Zhe Sun, Xiaoyu Du, Huiyuan Guo, Liang Zhao, Ming Zhang
Abstract
Alzheimer’s disease (AD) is distinguished by cognitive dysfunction and neuroinflammation in the brain. 2′-Fucosyllactose (2′-FL) is a major human milk oligosaccharide (HMO) that is abundantly present in breast milk and has been demonstrated to exhibit immunomodulatory effects. However, the role of 2′-FL and HMO in gut microbiota modulation in relation to AD remains insufficiently investigated. This study aimed to elucidate the preventive effect of the 2′-FL and HMO impact of AD and the relevant mechanism involved. Here, the behavioral results showed that 2′-FL and HMO intervention decreased the expression of Tau phosphorylation and amyloid-β (Aβ), inhibited neuroinflammation, and restored cognitive impairment in AD mice. The metagenomic analysis proved that 2′-FL and HMO intervention restored the dysbiosis of the gut microbiota in AD. Notably, 2′-FL and HMO intervention significantly enhanced the relative abundance of Clostridium and Akkermansia . The metabolomics results showed that 2′-FL and HMO enhanced the oleoyl- l -carnitine metabolism as potential drivers. More importantly, the levels of oleoyl- l -carnitine were positively correlated with the abundances of Clostridium and Akkermansia . These results indicated that 2′-FL and HMO had therapeutic potential to prevent AD-induced cognitive impairment, which is of great significance for the treatment of AD.