Western diet (rich in highly refined sugar and fat) can induce a range of metabolic dysfunctions in animals and humans, including neuroinflammation and cognitive function decline. Neuroinflammation and cognitive impairment, two critical pathological characteristics of Alzheimer’s disease, have been closely associated with microbial alteration via the gut-brain axis. Thus, the present study aimed to investigate the influence of 2-O-β-D-glucopyranosyl-L-ascorbic acid (AA-2βG) isolated from the fruits of Lycium barbarum on preventing the high-fructose diet (HFrD) induced neuroinflammation in mice. It was found that AA-2βG prevented HFrD-induced cognitive deficits. AA-2βG also predominantly enhanced the gut barrier integrity, decreased lipopolysaccharide entry into the circulation, which subsequently countered the activation of glial cells and neuroinflammatory response. These beneficial effects were transmissible by horizontal fecal microbiome transplantation, transferring from AA-2βG fed mice to HFrD fed mice. Additionally, AA-2βG exerted neuroprotective effects involving the enrichment of Lactobacillus and Akkermansia, potentially beneficial intestinal bacteria. The present study provided the evidence that AA-2βG could improve indices of cognition and neuroinflammmation via modulating gut dybiosis and preventing leaky gut. As a potential functional food ingredient, AA-2βG may be applied to attenuate neuroinflammation associated with Western-style diets.

西方饮食（富含高度精制的糖和脂肪）可引起动物和人类的一系列代谢功能障碍，包括神经炎症和认知功能下降。神经炎症和认知障碍是阿尔茨海默病的两个关键病理特征，与肠脑轴的微生物改变密切相关。因此，本研究旨在研究从枸杞果实中分离出的2- O - β - D-吡喃葡萄糖基-L-抗坏血酸（AA-2βG）的影响预防高果糖饮食（HFrD）引起的小鼠神经炎症。研究发现 AA-2βG 可以预防 HFrD 引起的认知缺陷。AA-2βG 还主要增强肠道屏障的完整性，减少脂多糖进入循环，从而对抗神经胶质细胞的激活和神经炎症反应。这些有益效果可通过粪便微生物组水平移植（从 AA-2βG 喂养的小鼠转移到 HFrD 喂养的小鼠）来传播。此外，AA-2βG 还具有神经保护作用，涉及乳酸杆菌和阿克曼氏菌的富集，潜在有益的肠道细菌。本研究提供的证据表明，AA-2βG 可以通过调节肠道微生态和预防肠漏来改善认知和神经炎症指数。作为一种潜在的功能性食品成分，AA-2βG 可用于减轻与西式饮食相关的神经炎症。