中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (5): 1076-1083.doi: 10.4103/1673-5374.355769

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

脊髓损伤后肠道菌群变化与代谢物谱相关

  

  • 出版日期:2023-05-15 发布日期:2022-11-01
  • 基金资助:
    中国国家自然科学基金项目（81771346，82071383）；山东省自然科学基金项目（重点项目）（ZR2020KH007）；山东省泰山市青年学者计划项目（tsqn201812156）；山东第一医科大学学术促进计划项目（2019QL025，2019RC021）；春季行业领导者人才支持计划项目（201984）；荣祥再生医学基金项目（2019SDRX-23）

Alterations in gut microbiota are related to metabolite profiles in spinal cord injury

Jian-Ning Kang1, Zheng-Fang Sun1, Xin-Yu Li2, Xiao-Di Zhang3, Zheng-Xin Jin1, Ce Zhang1, Ying Zhang1, Hui-Yun Wang1, #br# Na-Na Huang1, Jian-Hao Jiang2, 4, *, Bin Ning1, 2, *#br#   

  1. 1Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, China;  2Department of Spinal Surgery, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China;  3School of Clinical Medicine, Weifang Medical University, Weifang, Shandong Province, China;  4Department of Traumatic Orthopedics, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, Shandong Province, China
  • Online:2023-05-15 Published:2022-11-01
  • Contact: Bin Ning, MD, bning@sdfmu.edu.cn; Jian-Hao Jiang, MD, 15666128009@163.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 81771346, 82071383; the Natural Science Foundation of Shandong Province (Key Project), No. ZR2020KH007; the Taishan Scholar Youth Program of Shandong Province, No. tsqn201812156; Academic Promotion Program of Shandong First Medical University, Nos. 2019QL025, 2019RC021; Spring Industry Leader Talent Support Plan, No. 201984; and Rongxiang Regenerative Medicine Fund, No. 2019SDRX-23 (all to BN).

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摘要：

既往有研究认为肠道菌群代谢物可能通过血脊髓屏障进入中枢神经系统引起神经炎症，参与脊髓损伤后继发性损伤的发生。为探索肠道菌群与代谢物之间的相关性，以及肠道菌群对脊髓损伤继发性损伤影响的可能机制,实验构建了T8-T10创伤性脊髓损伤小鼠模型，利用 16S rRNA 基因扩增子测序和代谢组学来揭示 SCI 模型粪便样本中肠道微生物群和代谢物的变化。结果发现，脊髓损伤后，肠道微生物群发生了严重的紊乱，包括志贺氏菌、拟杆菌属、利肯氏菌、葡萄球菌、粘螺旋菌等促炎细菌增多，而乳酸杆菌、异芽孢杆菌、萨特氏菌等抗炎细菌减少。同时小鼠损伤脊髓中有27种代谢物水平下调，320种上调。进一步结合通路富集分析发现,其中L-亮氨酸、L-蛋氨酸、L-苯丙氨酸、L-异亮氨酸和L-缬氨酸这5种差异表达的氨基酸在激活脊髓损伤后的氧化应激和炎症反应中起关键作用。最后相关性分析表明，肠道菌群的改变与脊髓中氨基酸变化存在显著的相关性。因此推测肠道菌群的紊乱可能通过积累激活氧化应激和炎症反应的部分代谢物参与继发性损伤；这为通过粪便细菌移植改善脊髓损伤继发性损伤提供了新的理论基础。

https://orcid.org/0000-0002-7592-9485 (Bin Ning); http://orcid.org/0000-0002-3091-399X (Jian-Hao Jiang)

关键词: 脊髓损伤, 继发性损伤, 炎症, 肠道菌群, 代谢物, 氨基酸代谢, 16S rRNA基因扩增子测序, 代谢组学, 菌群失调, 代谢紊乱

Abstract: Studies have shown that gut microbiota metabolites can enter the central nervous system via the blood-spinal cord barrier and cause neuroinflammation, thus constituting secondary injury after spinal cord injury. To investigate the correlation between gut microbiota and metabolites and the possible mechanism underlying the effects of gut microbiota on secondary injury after spinal cord injury, in this study, we established mouse models of T8–T10 traumatic spinal cord injury. We used 16S rRNA gene amplicon sequencing and metabolomics to reveal the changes in gut microbiota and metabolites in fecal samples from the mouse model. Results showed a severe gut microbiota disturbance after spinal cord injury, which included marked increases in pro-inflammatory bacteria, such as Shigella, Bacteroides, Rikenella, Staphylococcus, and Mucispirillum and decreases in anti-inflammatory bacteria, such as Lactobacillus, Allobaculum, and Sutterella. Meanwhile, we identified 27 metabolites that decreased and 320 metabolites that increased in the injured spinal cord. Combined with pathway enrichment analysis, five markedly differential amino acids (L-leucine, L-methionine, L-phenylalanine, L-isoleucine and L-valine) were screened out, which play a pivotal role in activating oxidative stress and inflammatory responses following spinal cord injury. Integrated correlation analysis indicated that the alteration of gut microbiota was related to the differences in amino acids, which suggests that disturbances in gut microbiota might participate in the secondary injury through the accumulation of partial metabolites that activate oxidative stress and inflammatory responses. Findings from this study provide a new theoretical basis for improving the secondary injury after spinal cord injury through fecal microbial transplantation. 

Key words: 16S rRNA gene amplicon sequencing, amino acid metabolism, dysbacteriosis, gut microbiota, inflammation, metabolic disturbance, metabolites, metabolomics, secondary injury, spinal cord injury