基于“脑-肠”轴与肠道菌群探讨中医药防治阿尔茨海默病

TCM Prevention and Treatment of Alzheimer′s Disease Based on"Brain-Gut"Axis and Intestinal Flora

脑与大肠在生理上相互资助为用,在病理上也相互影响,肠道微生物通过传入信号通路和分泌生物活性物质影响大脑功能。故微生物-脑-肠轴(microbiome-brain-gut axis,MBGA)与阿尔茨海默病(Alzheimer′s disease,AD)的发生发展密切相关。中医药作为防治AD的重要手段,在MBGA的基础上,通过干预肠道菌群减少Aβ生成、降低tau磷酸化水平、减轻氧化应激、抑制神经炎症等,缓解AD发病症状,为临床防治AD提供新的方法及思路。然而目前仍然存在一些问题亟待解决:(1)大多研究观察中医药作用前后肠道菌群多样性的宏观差异,对中医药具体影响某一特定菌或菌群的研究较少;(2)中医药的作用机制复杂多变,作用于肠道菌群的靶点通路比较多,其作用机制有待深入研究;(3)对中医药防治AD的机制研究未在临床上得以验证,只有开展大样本、多中心的临床试验,才能更好地了解其作用机制,防治AD。未来,随着生物信息学和微生物基因组测序技术的不断成熟,可引入蛋白质组学、转录组学、脂质组学等与微生物组学协同合作,相互验证,为进一步深入研究肠道菌群和AD的关系提供技术支撑。

The brain and the large intestine support each other physiologically and affect each other pathologically,and the intestinal microbes affect brain function through afferent signaling pathways and secretion of bioactive substances.Therefore,the microbiome-brain-gut axis(MBGA)is closely related to the occurrence and development of Alzheimer′s disease(AD).As an important means for the prevention and treatment of AD,traditional Chinese medicine provides new methods and ideas for the clinical prevention and treatment of AD by intervening in the intestinal flora to reduce the production of Aβ,reduce the phosphorylation level of tau,reduce oxidative stress,and inhibit neuroinflammation based on MBGA.However,there are still some problems to be solved:(1)most studies are to observe the macroscopic differences in the diversity of intestinal microbiota before and after the action of traditional Chinese medicine,and there are few studies on the specific effects of traditional Chinese medicine on a specific bacteria or microflora,the mechanism of action of traditional Chinese medicine is complex and changeable,and there are many target pathways acting on the intestinal microbiota,and its mechanism of action needs to be further studied;(2)The research on the mechanism of TCM in the prevention and treatment of AD has not been verified in clinical practice,and only by carrying out large-sample,multi-center clinical trials can we better understand its mechanism of action and prevent and treat AD.In the future,with the continuous maturity of bioinformatics and microbial genome sequencing technologies,proteomics,transcriptomics,lipidomics,etc.can be introduced to cooperate with microbiome to verify each other,and provide technical support for further in-depth research on the relationship between intestinal microbiota and AD.