中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (9): 4122-4134.doi: 10.4103/NRR.NRR-D-25-00927

• 综述:退行性病与再生 • 上一篇    下一篇

微生物群-肠-脑轴及胆汁酸驱动的神经调节

  

  • 出版日期:2026-09-15 发布日期:2026-05-19
  • 基金资助:
    国家自然科学基金（82071182）和中国科学技术部项目基金（2022YFC3602604）

Microbiota–gut-brain axis and bile acids–driven neuromodulation

Taiwei Dong1, #, Tianyi Zhang1, #, Huanhuan Wang2, Jing Zhang3, Reema Abdullah4, Binggui Sun5, *, Guoping Peng1, *   

  1. 1Department of Neurology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; 
    2School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, Zhejiang Province, China; 
    3Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; 
    4Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; 
    5Department of Neurobiology and Department of Anesthesiology, the Children’s Hospital, Zhejiang University School of Medicine and National Clinical Research Center for Child Health; NHC and CAMS Key Laboratory of Medical Neurobiology, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
  • Online:2026-09-15 Published:2026-05-19
  • Contact: Guoping Peng, MD, guopingpeng@zju.edu.cn; Binggui Sun, PhD, bsun@zju.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 82071182; a grant from the Ministry of Science and Technology of China, No. 2022YFC3602604 (both to GP).

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摘要：

神胆汁酸作为具有双重肝源与微生物源的多功能信号分子，通过法尼醇X受体和G蛋白偶联受体5受体影响炎症与代谢过程，其功能紊乱在多种神经退行性疾病中均有体现。微生物群-肠-脑轴是胆汁酸驱动神经调节的关键通道，而性别特异性胆汁酸谱系与信号通路则引入了关键的生物学异质性。新兴转化证据既凸显了胆汁酸作为生物标志物与治疗靶点的潜力，也揭示了实现精准干预需克服的关键障碍。文章的核心发现包括3方面：①胆汁酸远非单纯的代谢副产物，而是调控神经炎症与能量代谢等核心病理过程的关键因子。其功能（无论是神经保护还是神经毒性）高度依赖于细胞类型和疾病特异性病理背景，呈现显著的“双刃剑”效应； ②“微生物群-胆汁酸-大脑轴”构成连接外周代谢紊乱与中枢神经系统病理的关键桥梁。③性别二态性作为基础生物学变量，对理解胆汁酸谱系异质性及疾病易感性至关重要。文章的核心贡献在于提出整合性“微生物群-胆汁酸-性别”框架，系统阐释了胆汁酸情境依赖性的双重作用。最终，倡导从传统脑中心视角向系统代谢视角的范式转变，确立胆汁酸系统作为未来精准治疗干预的潜在靶点。


https://orcid.org/0000-0002-6706-8670 (Guoping Peng); 

https://orcid.org/0000-0002-0386-6569 (Binggui Sun)

关键词: 阿尔茨海默病, 肌萎缩侧索硬化症, 胆汁酸, 中枢神经系统, 亨廷顿病, 微生物群-肠-脑轴, 神经退行性疾病, 帕金森病, 性别二态性, 治疗学

Abstract:

Bile acids emerge as multifunctional signaling molecules with dual hepatic and microbial origins, acting through farnesoid X receptor and Takeda G protein‑coupled receptor 5 to influence inflammation and metabolism. Their dysregulation is consistently observed across various neurodegenerative diseases. The microbiota–gut–brain axis is a pivotal conduit for bile acids-driven neuromodulation, while sex-specific bile acid profiles and signaling pathways introduce critical biological heterogeneity. Emerging translational evidence indicates the promise of bile acids as biomarkers and therapeutic targets, yet highlights the critical hurdles that need to be addressed to realize precision interventions. Our core findings are: (1) Bile acids are far more than mere metabolic byproducts. They orchestrate core pathological processes such as neuroinflammation and energy metabolism. Their functions, whether neuroprotective or neurotoxic, are highly context-dependent, varying with cell type and disease-specific pathological backgrounds, thus exhibiting a potent “double-edged sword” effect. (2) The “microbiota–bile acids–brain axis” serves as a crucial bridge linking peripheral metabolic dysregulation to central nervous system pathology. (3) Sexual dimorphism emerges as a fundamental biological variable essential for understanding the heterogeneity in bile acid profiles and disease susceptibility. The primary contribution of this work is the proposal of an integrated “microbiota-bile acids-sex” framework that systematically describes the key scientific challenge of the context-dependent, dual roles of bile acids. Ultimately, this review champions a paradigm shift from a traditional brain-centric view to a systemic, metabolic perspective, establishing the bile acid system as a promising target for future precision therapeutic interventions.

Key words: Alzheimer’s disease, amyotrophic lateral sclerosis, bile acids, central nervous system, Huntington’s disease, microbiota-gut-brain axis, neurodegenerative diseases, Parkinson’s disease, sexual dimorphism, therapeutics