中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (8): 3411-3425.doi: 10.4103/NRR.NRR-D-25-00434

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

肠道微生物群的神经保护机制和治疗前景

  

  • 出版日期:2026-08-18 发布日期:2026-04-25
  • 基金资助:
    国家自然科学基金(32200782)和吉林省科技发展计划项目(20240404014ZP)

Bidirectional communication between the gut microbiota and the central nervous system

Yingxian Liu1, #, Tuoxian Tang2, #, Hang Cai3, *, Zhenjiang Liu1, *   

  1. 1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin Province, China; 
    2Department of Biology, University of Pennsylvania, Philadelphia, PA, USA; 
    3Department of Pharmacy, The Second Hospital of Jilin University, Changchun, Jilin Province, China
  • Online:2026-08-18 Published:2026-04-25
  • Contact: Zhenjiang Liu, PhD, zhenjliu@jlu.edu.cn; Hang Cai, PhD, caihang10@163.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 32200782 (to ZL) and the Science and Technology Development Plan Project of Jilin Province, No. 20240404014ZP (to ZL).

摘要:

近年来,大量研究者对肠道微生物群与中枢神经系统之间的双向沟通产生了兴趣。这种沟通通过微生物群-肠道-大脑轴实现。随着年龄增长,人体微生物群的组成会发生显著变化,这些变化已被证实与多种神经退行性疾病的发生发展密切相关。此综述的目的在于探讨肠道与大脑之间复杂的双向信号传导通路,通过总结最新研究成果,阐述肠道微生物及其代谢物在调节炎症、维持肠道健康以及影响阿尔茨海默病、帕金森病和肌萎缩侧索硬化等神经退行性疾病发展过程中的关键作用。肠道微生物群通过多种方式影响大脑,例如,它可以产生短链脂肪酸等物质并激活炎症通路。动物和实验室模型研究显示,调节肠道微生物群可改善行为并减轻神经系统问题。近年来,宏基因组学和代谢组学研究表明,微生物群在维持机体健康中发挥着关键作用。微生物主要定植于肠道,参与宿主营养代谢、肠道结构完整性、肠道黏膜屏障维持及免疫调节。肠道微生物群通过双向微生物-肠道-脑轴与大脑进行沟通。肠道菌群的组成会随着年龄的增长发生显著变化,生态失调已被认定为衰老的十二大标志之一。近期研究将这些变化与多种与年龄相关的神经退行性疾病相关联,包括阿尔茨海默病、肌萎缩侧索硬化、帕金森病、多发性硬化和亨廷顿病。具体而言,肠道微生物群通过产生关键代谢物(如短链脂肪酸)及激活炎症和其他相关信号通路影响大脑。当前已有的临床研究通过粪便微生物群移植、益生菌和益生元等方法对肠道微生物群进行靶向调节,已显示出改善宿主行为结局的潜力。因此,基于肠道微生物群的治疗为神经系统疾病的治疗带来了新希望,但由于肠道微生物群的复杂性以及这些治疗可能存在不良反应,研究者们在临床广泛应用前需谨慎评估其安全性和有效性。


https://orcid.org/0000-0003-2320-7613 (Zhenjiang Liu); https://orcid.org/0009-0006-1361-3094 (Hang Cai)

关键词: 阿尔茨海默病, 肌萎缩侧索硬化, 菌群失调, 肠道微生物群, 亨廷顿病, 炎症, 微生物群-肠-脑轴, 神经退行性疾病, 帕金森病, 迷走神经

Abstract: In recent years, an increasing number of researchers have become interested in the bidirectional communication between the gut microbiota and the central nervous system. This communication occurs through the microbiota-gut-brain axis. As people age, the composition of the gut microbiota undergoes considerable changes, which are now known to play an important role in the development of many neurodegenerative diseases. This review aims to investigate the complex bidirectional signaling pathways between the gut and the brain. It summarizes the latest research findings on how the gut microbiota and its metabolites play critical roles in regulating inflammation, maintaining gut health, and influencing the development of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. The review also analyzes the current clinical applications of gut microbiota-based treatments for neurological disorders, including fecal microbiota transplantation, probiotics, and prebiotics. Many studies show that the gut microbiota affects the brain in several ways. For example, it can produce substances such as short-chain fatty acids and activate inflammatory pathways. Studies involving animals and laboratory models have demonstrated that adjusting the gut microbiota can help improve behavior and reduce neurological problems. Recent metagenomic and metabolomics studies have shown that the microbiota plays a crucial role in maintaining the organism’s health. Microorganisms primarily colonize the gut and are involved in host nutrient metabolism, maintaining the structural integrity of the intestine, preserving the intestinal mucosal barrier, and modulating the immune system. The gut microbiota communicates with the brain through a bidirectional microbiota-gut-brain axis. The composition of the gut flora changes considerably with age, and ecological dysregulation has been recognized as one of the twelve most recent hallmarks of aging. Recent studies have linked these changes to a variety of age-related neurological disorders, including Alzheimer’s disease, amyotrophic lateral sclerosis, Parkinson’s disease, multiple sclerosis, and Huntington’s disease. Specifically, the gut microbiota influences the brain through the production of key metabolites such as short-chain fatty acids and the activation of inflammatory and other relevant signaling pathways. In preclinical studies, targeted modulation of the gut microbiota, through methods such as fecal microbiota transplantation, probiotics, and prebiotics, has demonstrated potential in improving host behavioral outcomes. Therefore, gut microbiota-based treatments offer new hope for the treatment of nervous system diseases. However, due to the complexity of the gut microbiota and the potential adverse reactions associated with these therapies, researchers need to carefully assess their safety and efficacy before widespread clinical application. 

Key words: Alzheimer’s disease, amyotrophic lateral sclerosis, dysbiosis, gut microbiota, Huntington’s disease, inflammation, microbiota–gut–brain axis, neurodegenerative diseases, Parkinson’s disease, vagus nerve