As a traditional drug–food homologous plant, Dendrobium officinale is widely recognized for its nutritional and medicinal value. Specifically, D. officinale polysaccharide (DOP) has garnered attention as a potential prebiotic for its protective effects on gut microbiota and the nervous system. However, the underlying mechanism by which DOP improves cognitive dysfunction in Alzheimer’s disease (AD) remains unclear. This study intends to elucidate the beneficial effects of DOP on AD mice from the perspectives of metabolomics and the intestinal microbiome. The results showed that DOP significantly ameliorated cognitive dysfunction, attenuated hippocampal neuronal damage and Aβ plaque deposition, and restored intestinal barrier integrity in AD mice. The antibiotic-cocktail-induced germ-free mouse model confirmed that the neuroprotective effect of DOP was dependent on gut microbiota. Further investigations demonstrated that DOP influenced the composition of gut microbiota and restored its diversity. Additionally, DOP reshaped metabolic profile disorders in AD mice and increased the short-chain fatty acids (SCFAs) content. Correlation analysis further highlighted that specific gut microbiota was associated with the metabolism of AD mice. In conclusion, this study sheds light on the positive impact of DOP in reshaping the gut microbiota and enhancing cognitive function, offering important perspectives for the possible advancement and utilization of DOP.

中文翻译：

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破译铁皮石斛多糖干预阿尔茨海默病小鼠的治疗效果和潜在机制：来自代谢组学和微生物组的见解


作为一种传统的药食同源植物，铁皮石斛因其营养和药用价值而得到广泛认可。具体来说，铁皮石斛多糖 （DOP） 因其对肠道微生物群和神经系统的保护作用而作为一种潜在的益生元而受到关注。然而，DOP 改善阿尔茨海默病 （AD） 认知功能障碍的潜在机制仍不清楚。本研究旨在从代谢组学和肠道微生物组的角度阐明 DOP 对 AD 小鼠的有益影响。结果显示，DOP 可显著改善 AD 小鼠的认知功能障碍，减轻海马神经元损伤和 Aβ 斑块沉积，并恢复肠道屏障完整性。抗生素鸡尾酒诱导的无菌小鼠模型证实 DOP 的神经保护作用取决于肠道菌群。进一步的研究表明，DOP 影响肠道菌群的组成并恢复其多样性。此外，DOP 重塑了 AD 小鼠的代谢谱障碍并增加了短链脂肪酸 （SCFAs） 含量。相关性分析进一步强调，特定的肠道菌群与 AD 小鼠的代谢有关。综上所述，本研究阐明了 DOP 在重塑肠道菌群和增强认知功能方面的积极影响，为 DOP 的可能进步和利用提供了重要视角。