School of life Sciences, Anhui University, Hefei, 230601, P. R. China.
Key Laboratory for Ecological Engineering and Biotechnology of Anhui Province, Hefei, 230601, P. R. China.
Mol Nutr Food Res. 2024 Apr;68(7):e2300739. doi: 10.1002/mnfr.202300739. Epub 2024 Mar 25.
Age-related cognitive decline is primarily attributed to the progressive weakening of synaptic function and loss of synapses, while age-related gut microbial dysbiosis is known to impair synaptic plasticity and cognitive behavior by metabolic alterations. To improve the health of the elderly, the protective mechanisms of Oudemansiella raphanipes polysaccharide (ORP-1) against age-related cognitive decline are investigated. The results demonstrate that ORP-1 and its gut microbiota-derived metabolites SCFAs restore a healthy gut microbial population to handle age-related gut microbiota dysbiosis mainly by increasing the abundance of beneficial bacteria Dubosiella, Clostridiales, and Prevotellaceae and reducing the abundance of harmful bacteria Desulfovibrio, strengthen intestinal barrier integrity by abolishing age-related alterations of tight junction (TJ) and mucin 2 (MUC2) proteins expression, diminish age-dependent increase in circulating inflammatory factors, ameliorate cognitive decline by reversing memory- and synaptic plasticity-related proteins levels, and restrain hyperactivation of microglia-mediated synapse engulfment and neuroinflammation. These findings expand the understanding of prebiotic-microbiota-host interactions.
年龄相关性认知衰退主要归因于突触功能的逐渐减弱和突触的丧失，而年龄相关性肠道微生物失调已知通过代谢改变损害突触可塑性和认知行为。为了改善老年人的健康，研究了金针菇多糖（ORP-1）对年龄相关性认知衰退的保护机制。结果表明，ORP-1 及其肠道微生物衍生的代谢物 SCFAs 通过增加有益菌 Dubosiella、Clostridiales 和 Prevotellaceae 的丰度和降低有害菌 Desulfovibrio 的丰度，恢复健康的肠道微生物种群，从而主要处理年龄相关性肠道微生物失调，加强肠道屏障完整性，消除紧密连接（TJ）和粘蛋白 2（MUC2）蛋白表达的年龄相关性改变，减少循环炎症因子的年龄依赖性增加，通过逆转与记忆和突触可塑性相关的蛋白水平改善认知衰退，并抑制小胶质细胞介导的突触吞噬和神经炎症的过度激活。这些发现扩展了对益生菌-微生物群-宿主相互作用的理解。
