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): 4100-4111.doi: 10.4103/NRR.NRR-D-25-01016

• 综述:脊髓损伤修复保护与再生 • 上一篇    下一篇

超越肠-脑轴：肠-脊髓轴双向调节的新范式

  

  • 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（81701199；82503076）；上海市2024年《科技创新行动计划》创新药物与医疗器械应用示范项目（24SF1902800）；上海市杰出青年人才计划项目（24SF1902800）；上海市卫生健康委员会优秀青年人才计划（2022YQ003）；长海医院长虹人才计划

A new paradigm of bidirectional regulation of the gut– spinal cord axis

Songzhi Ni1, #, Kai Chen1, #, Haojue Wang1, #, Shenyuan Chen2, #, Yuanyu Qiu3, Tianjiao Wang4, 5, Fengfeng Mo6, 7, Shige Wang8, Bo Li9, *, Yushu Bai1, *, Jiulong Zhao4, *, Xiao Zhai1, *, Zhaoshen Li4   

  1. 1Department of Orthopedics, Shanghai Changhai Hospital, Shanghai, China; 
    2Zhenjiang Key Laboratory of High Technology Research on sEVs Foundation and Transformation Application, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China; 
    3Department of Gynecology and Obstetrics, the Affiliated Jiangyin Hospital of Southeast University, Jiangyin, Jiangsu Province, China; 
    4Department of Gastroenterology, Shanghai Changhai Hospital, Shanghai, China; 
    5National Digestive Endoscopy Improvement System, Shanghai, China; 
    6Department of Naval Nutrition and Food Hygiene, Naval Medical University, Shanghai, China; 
    7Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, Shanghai Changhai Hospital, Shanghai, China; 
    8School of Materials and Chemistry, University of Shanghai for Science and Technology, Shanghai, China; 
    9Department of Orthopedics, Shanghai Changzheng Hospital, Shanghai, China

  • Online:2026-09-15 Published:2026-05-19
  • Contact: Xiao Zhai, MD, drzhaixiao@126.com; Jiulong Zhao, MD, jlzhao9@163.com; Yushu Bai, MD, spinebaiys@163.com; Bo Li, MD, smmulibo@163.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 81701199 (to XZ), 82503076 (to KC); Application Demonstration Project for Innovative Drugs and Medical Devices under Shanghai’s 2024 “Science and Technology Innovation Action Plan”, No. 24SF1902800 (to YB); the Excellent Young Talent Program of Shanghai Municipal Health Commission, No. 2022YQ003 (to XZ); Changhong Talent Program of Changhai Hospital (to XZ).

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摘要：

脊髓损伤、多发性硬化症和肌萎缩性侧索硬化症与肠道的双向交互作用是通过独特的肠-脊髓轴实现的，而非完全由传统的肠-脑轴所解释。脊髓凭借其独特的解剖与生理特征，成为沟通枢纽的核心节点。肠道与脊髓通过免疫系统、自主神经系统及肠神经系统等多重通路实现交互。文章综述了肠道稳态与脊髓疾病关联性的现有临床及基础研究。研究框架如下：①基于流行病学研究发现，脊髓疾病患者常伴随肠道功能紊乱，其病因可能涉及抗生素暴露与环境因素。②维持肠道健康的关键生理结构与解剖结构——肠道屏障、肠道菌群及肠神经系统，以及参与脊髓神经调控的感觉神经元、运动神经元和中间神经元。③微生物轴、免疫轴和神经轴三大轴系在双向调节与病理机制中的发挥重要作用，这些轴系间的恶性循环可能加剧脊髓疾病。④文章概述了肠-脊髓轴内的潜在生物标志物，如尿苷、次黄嘌呤和5-甲氧色氨酸，并提出若干具有临床应用潜力的治疗策略，包括粪便微生物群移植及益生菌与益生元的应用。⑤文章强调肠-脊髓轴作为有前景的治疗靶点，着重指出需通过多组学整合、纵向队列研究及个性化干预来化解现有争议。总体而言，对肠-脊髓轴的认知实现了超越肠-脑框架的概念性突破。


http://orcid.org/0000-0003-4236-2264 (Xiao Zhai); 

http://orcid.org/0009-0007-7477-7719 (Jiulong Zhao); 

http://orcid.org/0000-0002-8216-031X (Yushu Bai);
http://orcid.org/0000-0001-5079-6404 (Bo Li)

关键词: 神经炎症, 肠道微生物群, 肠神经系统, 自主神经调节, 微生物代谢物, 肠道屏障, 宿主-微生物相互作用, 神经退行性变, 多组学方法, 生物标志物

Abstract: The bidirectional interactions of spinal cord injury, multiple sclerosis, and amyotrophic lateral sclerosis with the gut operate through a distinct gut–spinal cord axis, rather than being fully explained by the conventional gut–brain axis. The spinal cord, with its unique anatomical and physiological features, serves as a central hub of communication. The gut and spinal cord communicate through various pathways, including the immune system and the autonomic and enteric nervous systems. This review summarizes existing clinical and basic research on the relationship between gut homeostasis and spinal cord diseases. First, we present findings from epidemiological studies showing that patients with spinal cord disorders often exhibit altered gut function, which may be influenced by antibiotic exposure and environmental factors. Second, we review the key physiological and anatomical structures of the gut-spinal cord axis, including the intestinal barrier, gut microbiota, and enteric nervous system, all of which are involved in maintaining gut health, as well as sensory neurons, motor neurons, and interneurons in spinal nerve regulation. Third, we describe the roles of the three axes (microbial, immune, and neural) in bidirectional regulation and their pathological mechanisms. Moreover, vicious cycles involving these axes can exacerbate spinal cord disorders. Fourth, we outline potential biomarkers in the gut–spinal cord axis, such as uridine, hypoxanthine, and 5-methoxytryptophan. Fifth, we propose several treatment strategies with potential clinical applications, including fecal microbiota transplantation and the use of probiotics and prebiotics. Finally, this review emphasizes the gut–spinal cord axis as a promising therapeutic target, highlighting the need for multi-omics integration, longitudinal cohort studies, and individualized interventions to resolve existing debates. Overall, the recognition of the gut–spinal cord axis provides a conceptual shift that extends beyond the gut–brain framework.

Key words: autonomic regulation, biomarkers, enteric nervous system, gut microbiota, host-microbe interaction, intestinal barrier, microbial metabolites, multi-omics approaches, neurodegeneration, neuroinflammation