2′-Fucosyllactose Ameliorates Cognitive Impairment and Neuroinflammation in AD Mice

2′-Fucosyllactose (2′-FL) supplementation is beneficial to brain function. Our previous study has already reported the prevention of AD by 2′-FL in mice; in this study, the effects of 2′-FL in AD were evaluated. Five month-old male 5 × FAD mice were gavaged with 2′-FL for 11 weeks, and 2 mg of 2′-FL significantly improved cognitive deficits, even restoring them to the normal level. The destroyed neurons, damaged synaptic plasticity characterized by decreased cholinergic neurons and glutaminergic neurons, and the activation of microglial cells were all significantly improved by 2′-FL. 2′-FL also significantly down-regulated mRNA expression of Il-6 and Il-1 β and alleviated oxidative damages through the Keap1–Nrf2 pathway to up-regulate Nqo1 expression. AD-increased PC (18:4/20:5) and DG (18:4/22:6/0:0) in the feces and serum were both decreased by 2′-FL, which was significantly positively correlated with inflammation and negatively correlated with synaptic plasticity. This study lays a theoretical basis for the application of 2′-FL in neurodegenerative diseases.