脊髓损伤患者肠道菌群属水平的特征及意义

doi:10.3969/j.issn.1006-9771.2020.00.003

《中国康复理论与实践》 ›› 2020, Vol. 26 ›› Issue (4): 393-399.doi: 10.3969/j.issn.1006-9771.2020.00.003

• 专题脊髓损伤原因及机制 • 上一篇下一篇

脊髓损伤患者肠道菌群属水平的特征及意义

汪俊宇^1,²,庞日朝¹,王文春¹,王美玉³,向武¹,赵小华¹,张安仁¹()

1.中国人民解放军西部战区总医院康复医学科,四川成都市 610083
2.四川大学生物治疗国家重点实验室,四川成都市 610041
3.西南财经大学天府学院,四川成都市 610052

收稿日期:2019-03-28 修回日期:2019-08-21 出版日期:2020-04-25 发布日期:2020-04-27
通讯作者: 张安仁 E-mail:1518526780@qq.com
作者简介:汪俊宇(1993-),男,汉族,重庆市人,硕士研究生,主要研究方向：脊髓损伤康复的临床及基础研究。
基金资助:
1.国家自然科学基金面上项目(81674044);1.国家自然科学基金面上项目(81973927);2.四川省卫计委普及应用项目(18PJ509);3.四川省医学会青年创新科研课题(Q17007)

Characteristics of Genus-level Gut Microbiome in Patients with Spinal Cord Injury

WANG Jun-yu^1,²,PANG Ri-zhao¹,WANG Wen-chun¹,WANG Mei-yu³,XIANG Wu¹,ZHAO Xiao-hua¹,ZHANG An-ren¹()

1. Department of Rehabilitation Medicine, the General Hospital of Western Theater Command, Chengdu, Sichuan 610083, China
2. State Key Laboratory of Biotherapy of Sichuan University, Chengdu, Sichuan 610041, China
3. Tianfu College, Southwestern University of Finance and Economics, Chengdu, Sichuan 610052, China

Received:2019-03-28 Revised:2019-08-21 Published:2020-04-25 Online:2020-04-27
Contact: ZHANG An-ren E-mail:1518526780@qq.com
Supported by:
National Natural Science Foundation of China(81674044);National Natural Science Foundation of China(81973927);Popularization and Application Project of Sichuan Health Planning Commission(18PJ509);Youth Innovation Research Project of Sichuan Medical Association(Q17007)

摘要/Abstract

摘要：

目的探讨脊髓损伤患者肠道菌群属水平变化特征及其在临床康复中的意义。方法 2018年1月至12月,纳入脊髓损伤患者23例(患者组)和健康受试者21例(对照组),采集粪便样本,应用16S rDNA高通量测序检测肠道菌群,并采用物种组成分析及随机森林机器学习等生物信息学方法分析两组间属水平的菌群分布及差异。结果患者组丰度升高的重要标志性菌属分别是：瘤胃菌科的UBA1819、Ruminiclostridium 9、Ruminococcaceae NK4A214 group、Ruminococcus 2、Ruminococcaceae UCG-005、Ruminiclostridium 5、Flavonifractor;理研菌科的Alistipes、dgA-11 gut group、Rikenellaceae RC9 gut group;毛螺菌科的[Eubacterium] oxidoreducens group;消化链球菌科的Intestinibacter;肠杆菌科的Escherichia-Shigella (志贺菌属);以及Tannerellaceae的Parabacteroides (|U| > 1.962, P< 0.05)。患者组丰度降低的是梭杆菌科Fusobacterium菌属(|U| = -2.284, P< 0.05)。结论脊髓损伤患者肠道菌群与健康对照组存在差异。脊髓损伤患者与抑郁相关的瘤胃菌科、与中枢神经系统疾病关系密切的瘤胃球菌,以及肠道内致病菌消化链球菌属、志贺菌属等的相对丰度增加;对肠道有益的产丁酸盐菌和抗炎性菌属的相对丰度降低。这些菌群变化可能有一定的临床意义。

关键词: 脊髓损伤, 肠道菌群, 临床康复

Abstract:

Objective To investigate the changes of genus-level gut microbiome in patients with spinal cord injury and its significance in clinical rehabilitation.Methods Fecal samples were collected from 23 patients with spinal cord injury (patients group) and 21 healthy volunteers (control group). Gut microbiome was detected by 16S rDNA high-throughput sequencing. Bioinformatics methods such as species composition analysis and Random Forest were used to analyze the distribution and difference of genus-level gut microbiome between two groups. Results Compared with the control group, the increased important marker genera in the patients group were as follows: UBA1819, Ruminiclostridium 9, Ruminococcaceae NK4A214 group, Ruminococcus 2, Ruminococceae UCG-005, Ruminiclostridium 5, Flavonifractor belonging to Ruminococceae; Aglistes, dgA-11 gut group, Rikenaceae RC9 gut group belonging to Rikenellaceae; [Eubacterium] oxidoreducens group belonging to Lachnospiraceae; Intestinibacter belonging to Peptostreptococcaceae; Escherichia-Shigella belonging to Enterobacteriaceae; Tannerellaceae belonging to Parabacteroides (|U| > 1.962, P< 0.05). The decreased marker genera in the patients group was Fusobacterium of Fusobacteriaceae (|U| = -2.284, P< 0.05).Conclusion There are significant differences of gut microbiome in spinal cord injury patients. The relative abundance of Ruminococcaceae relating to depression, Ruminococcus relating to central nervous system diseases, and enteropathogenic bacteria such as Escherichia-Shigella and Erysipelothrix increase; and the relative abundance of butyrate-producing bacteria and anti-inflammatory bacteria benefitting to the intestine decrease; which may play a role in clinic.

Key words: spinal cord injury, gut microbiome, clinical rehabilitation

中图分类号:

R651.2

汪俊宇,庞日朝,王文春,王美玉,向武,赵小华,张安仁. 脊髓损伤患者肠道菌群属水平的特征及意义[J]. 《中国康复理论与实践》, 2020, 26(4): 393-399.

WANG Jun-yu,PANG Ri-zhao,WANG Wen-chun,WANG Mei-yu,XIANG Wu,ZHAO Xiao-hua,ZHANG An-ren. Characteristics of Genus-level Gut Microbiome in Patients with Spinal Cord Injury[J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2020, 26(4): 393-399.

图/表 5

表1

表2

表3

图1

表4

参考文献 29

[1]	Savage D C. Microbial ecology of the gastrointestinal tract[J]. Annu Rev Microbiol, 1977, 31:107-133. pmid: 334036
[2]	Backhed F, Ley R E, Sonnenburg J L, et al. Host-bacterial mutualism in the human intestine[J]. Science, 2005, 307:1915-1920. doi: 10.1126/science.1104816
[3]	Belkaid Y, Naik S. Compartmentalized and systemic control of tissue immunity by commensals[J]. Nat Immunol, 2013, 14(7):646-653. doi: 10.1038/ni.2604
[4]	Round J L. The gut microbiota shapes intestinal immune responses during health and disease[J]. Nat Rev Immunol, 2009, 9(8):600. doi: 10.1038/nri2614
[5]	Hooper L V, Littman D R, Macpherson A J, et al. Interactions between the microbiota and the immune system[J]. Science, 2012, 336(6086):1268-1273. doi: 10.1126/science.1223490
[6]	Nicholson J K, Holmes E, Kinross J, et al. Host-gut microbiota metabolic interactions[J]. Science, 2012, 336(6086):1262-1267. doi: 10.1126/science.1223813
[7]	Scheperjans F, Aho V, Pereira P A, et al. Gut microbiota are related to Parkinson's disease and clinical phenotype[J]. Mov Disord, 2015, 30(3):350-358. doi: 10.1002/mds.v30.3
[8]	Mielcarz D W, Kasper L H. The gut microbiome in multiple sclerosis[J]. Curr Treat Options Neurol, 2015, 17(4):344.
[9]	Vogt N M, Kerby R L, Dill-Mcfarland K A, et al. Gut microbiome alterations in Alzheimer’s disease[J]. Sci Rep, 2017, 7(1):13537. doi: 10.1038/s41598-017-13601-y
[10]	Wang L, Conlon M A, Christophersen C T, et al. Gastrointesti- nal microbiota and metabolite biomarkers in children with autism spectrum disorders[J]. Biomark Med, 2014, 8(3):331-344. doi: 10.2217/bmm.14.12 pmid: 24712423
[11]	Mazzini L, Mogna L, De Marchi F, et al. Potential role of gut microbiota in ALS pathogenesis and possible novel therapeutic strategies[J]. J Clin Gastroenterol, 2018, 52 (Suppl 1). Proceedings from the 9th Probiotics, Prebiotics and New Foods, Nutraceuticals and Botanicals for Nutrition & Human and Microbiota Health Meeting, held in Rome, Italy from September 10 to 12, 2017:S68-S70. doi: 10.1097/MCG.0000000000001042. doi: 10.1097/MCG.0000000000001042
[12]	Kigerl K A, Hall J C E, Wang L, et al. Gut dysbiosis impairs recovery after spinal cord injury[J]. J Exp Med, 2016, 213(12):2603-2620. doi: 10.1084/jem.20151345
[13]	Gungor B, Adiguzel E, Gursel I, et al. Intestinal microbiota in patients with spinal cord injury[J]. PLoS One, 2016, 11(1):e0145878. doi: 10.1371/journal.pone.0145878
[14]	张洁, 李建军, 张超, 等. 急性创伤性完全性脊髓损伤患者肠道菌群多样性研究[J]. 中国康复理论与实践, 2019, 25(12):1450-1457.
[15]	美国脊髓损伤协会, 国际脊髓损伤学会. 脊髓损伤神经学分类国际标准(2011年修订)[J]. 李建军,王方永,译. 中国康复理论与实践, 2011, 17(10):963-972.
[16]	王一吉, 周红俊, 李建军, 等. 脊髓损伤神经学分类国际标准检查表最新修订及解读[J]. 中国康复理论与实践, 2015, 21(8):879-882.
[17]	Caporaso J G, Lauber C L, Walters W A, et al. Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample[J]. Proc Natl Acad Sci USA, 2011, 108(Suppl 1):4516-4522. doi: 10.1073/pnas.1000080107
[18]	Liu C, Yao M J, Stegen J C, et al. Long-term nitrogen addition affects the phylogenetic turnover of soil microbial community responding to moisture pulse[J]. Sci Rep, 2017, 7:17492. doi: 10.1038/s41598-017-17736-w
[19]	李欣, 刘冯铂, 杜若飞, 等. 残疾人领悟社会支持对其社交回避及苦恼的影响:自尊的调节作用[J]. 心理技术与应用, 2016, 4(11):648-655.
[20]	荣晗, 徐丹, 刘铁榜, 等. 抑郁症患者肠道菌群丰度和种类及基因功能通路的病例对照研究[J]. 中华精神科杂志, 2017, 50(3):208-213.
[21]	Mar G, Sevasti G, Santos P G, et al. Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior[J]. eLife, 2016, 5:e13442. doi: 10.7554/eLife.13442
[22]	Mudd A T, Berding K, Wang M, et al. Serum cortisol mediates the relationship between fecal Rumi- nococcus & brain N-acetylaspartate in the young pig[J]. Gut Microbes, 2017, 8(6):589-600. doi: 10.1080/19490976.2017.1353849
[23]	Zhao L, Huang Y, Lu L, et al. Saturated long-chain fatty acid-producing bacteria contribute to enhanced colonic motility in rats[J]. Microbiome, 2018, 6(1):107. doi: 10.1186/s40168-018-0492-6
[24]	彭俊平, 杨剑, 金奇, 等. 志贺菌研究进展[J]. 中国科学:生命科学, 2010(1):14-22.
[25]	Meijer K, de Vos P, Priebe M G. Butyrate and other short-chain fatty acids as modulators of immunity: what relevance for health?[J]. Curr Opin Clin Nutr Metab Care, 2010, 13(6):715-721. doi: 10.1097/MCO.0b013e32833eebe5
[26]	Fung K Y, Cosgrove L, Lockett T, et al. A review of the potential mechanisms for the lowering of colorectal oncogenesis by butyrate[J]. Br J Nutr, 2012, 108(5):820-831. doi: 10.1017/S0007114512001948
[27]	Vinolo M A, Rodrigues H G, Hatanaka E, et al. Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils[J]. J Nutr Biochem, 2011, 22(9):849-855. doi: 10.1016/j.jnutbio.2010.07.009
[28]	Park J S, Woo M S, Kim S Y, et al. Repression of interferon-gamma-induced inducible nitric oxide synthase (iNOS) gene expression in microglia by sodium butyrate is mediated through specific inhibition of ERK signaling pathways[J]. J Neuroimmunol, 2005, 168(1-2):56-64. doi: 10.1016/j.jneuroim.2005.07.003
[29]	Chen P S, Wang C C, Bortner C D, et al. Valproic acid and other histone deace- tylase inhibitors induce microglial apoptosis and attenuate lipopolysacchar- ide-induced dopaminergic neurotoxicity[J]. Neuroscience, 2007, 149(1):203-212. pmid: 17850978

序号	性别	年龄(岁)	病程(月)	损伤平面	ASIA	NBD评分	血液白细胞数(10⁹/L) 参考值(3.5~9.5)×10⁹/L	尿液白细胞(/μl) 参考值(0~25)/μl	尿液细菌(/μl) 参考值(0~1000)/μl
1	女	27	72	L₂	D	8	8.68	24.3	16.3
2	男	32	62	C₄	A	11	8.12	5.3	895.9
3	男	43	48	L₁	D	3	7.48	18.8	184.2
4	男	30	49	C₄	B	4	4.49	27.5	5.7
5	男	28	108	T₁₀	A	11	6.15	17.5	3.8
6	男	24	13	C₄	C	11	7.34	21.0	1195.0
7	男	41	7	C₆	B	20	3.98	24.3	1214.0
8	男	37	6	C₄	C	8	5.11	28.9	665.9
9	男	27	63	C₅	A	11	6.4	3.3	18.2
10	男	36	1	T₄	B	15	6.57	30.9	141.1
11	男	32	3	T₁₀	A	21	6.42	22.7	51.4
12	女	50	2	T₈	A	15	5.36	4.4	4.7
13	男	51	2	T₁₂	A	28	8.13	4.0	0.9
14	男	31	48	T₆	A	8	7.44	34.8	982.0
15	女	44	96	T₁₂	A	8	5.95	16.2	226.0
16	男	45	24	T₁₀	A	11	7.67	31.4	1108.0
17	女	41	300	T₈	A	15	5.83	5.8	23.7
18	男	35	99	T₁₀	A	15	4.84	102.4	519.3
19	女	42	110	T₄	A	11	5.28	21.1	341.9
20	男	39	97	T₁₀	A	11	6.17	54.9	668.3
21	男	42	135	T₁₀	A	3	5.31	22.9	371.5
22	男	26	2	C₄	B	20	6.27	17.2	0.9
23	男	22	2	C₅	A	21	7.27	23.1	848.6

组别	n	性别 (男/女,n)	年龄	NBD评分
对照组	21	16/5	37.05±7.871
患者组	23	18/5	35.87±8.275	12.57±6.298
χ²/t值		0	-0.471
P值		1.000	0.638

属	对照组	患者组	U值	P值
Bacteroides	12.049(7.485, 39.991)	27.987(11.524, 37.853)	-0.905	0.366
Megamonas	1.372(0.209, 26.425)	0.595(0.506, 1.100)	-0.834	0.404
Prevotella 9	0.578(0.249, 29.321)	0.949(0.721, 3.662)	-0.552	0.581
[Eubacterium] coprostanoligenes group	2.034 (0.949, 10.812)	5.540(2.271, 11.321)	-1.701	0.088
Ruminococcaceae UCG-002	3.143(1.066, 7.966)	3.699(1.398, 5.895)	-0.012	0.991
Escherichia-Shigella	0.702(0.632, 1.553)	1.594(0.936, 4.997)	-1.962	0.05
Lachnospiraceae NC2004 group	1.556(0.651, 3.501)	1.007(0.677, 2.416)	-0.341	0.733
Lachnospiraceae UCG-008	0.942(0.398, 1.863)	1.758(1.075, 4.136)	-2.385	0.017
Lachnospiraceae NK4A136 group	1.151(0.468, 4.358)	1.758(0.639, 2.460)	-0.141	0.888
[Eubacterium] eligens group	1.044(0.439, 3.653)	0.506(0.221, 0.797)	-1.774	0.076
Alistipes	0.228(0.126, 0.37)	1.113(0.398, 3.295)	-3.537	< 0.001
Parabacteroides	0.449(0.196, 0.92)	1.651(0.784, 3.588)	-3.302	0.001
Phascolarctobacterium	1.082(0.376,1.619)	1.075(0.133, 2.959)	-0.400	0.690
Ruminococcaceae UCG-014	0.070(0.009, 0.234)	0.082(0.057, 0.126)	-1.340	0.180
Megasphaera	0.829(0.455, 1.049)	1.100(0.651, 1.929)	-1.071	0.284
[Ruminococcus] torques group	0.734(0.338,1.049)	1.436(0.835,1.929)	-2.362	0.018
Enterobacter	0.240 (0.126, 1.837)	0.468(0.139, 1.663)	-0.376	0.707
Roseburia	0.892(0.085, 2.093)	0.487(0.209, 1.479)	-0.505	0.613
Lachnospiraceae UCG-004	0.525(0.289, 0.889)	0.569(0.361, 0.791)	-0.423	0.672
Prevotella 2	0.082(0.013, 1.021)	0.089(0.044, 0.183)	-0.165	0.869
Fusobacterium	0.101(0.016, 0.367)	0.025(0.013, 0.057)	-2.284	0.022

差异菌群	Gini指数	对照组	患者组	U值	P值
UBA1819	0.65	0.019(0, 0.032)	0.133(0.038, 0.285)	-4.227	< 0.001
Ruminiclostridium 9	0.58	0.057(0.028, 0.117)	0.240(0.108, 0.342)	-4.011	< 0.001
Alistipes	0.50	0.228(0.126, 0.379)	1.113(0.398, 3.295)	-3.537	< 0.001
RuminococcaceaeNK4A214 group	0.47	0.171(0.079, 0.250)	0.841(0.304, 1.644)	-3.369	< 0.001
[Eubacterium] oxidoreducens group	0.47	0.025(0.003, 0.054)	0.089(0.038, 0.164)	-3.314	< 0.001
Ruminococcus 2	0.47	0.120(0.411, 0.294)	0.499(0.272, 1.758)	-3.819	< 0.001
Ruminococcaceae UCG-005	0.43	0.076(0.047, 0.262)	0.329(0.196, 1.107)	-3.444	< 0.001
dgA-11 gut group	0.29	0.019(0.003, 0.022)	0.038(0.019, 0.069)	-3.257	0.001
Rikenellaceae RC9 gut group	0.26	0.063(0.016, 0.152)	0.133(0.101, 0.196)	-2.281	0.023
Ruminiclostridium 5	0.23	0.069(0.028, 0.152)	0.171(0.126, 0.247)	-2.882	0.004
Fusobacterium	0.22	0.101(0.016, 0.367)	0.025(0.013, 0.057)	-2.284	0.022
Intestinibacter	0.22	0(0, 0.009)	0.025(0.006, 0.051)	-3.362	< 0.001
Flavonifractor	0.22	0.013(0.006, 0.038)	0.057(0.019, 0.152)	-3.211	0.001
Escherichia-Shigella	0.21	0.702(0.632, 1.553)	1.594(0.936, 4.997)	-1.962	0.050
Parabacteroides	0.21	0.449(0.196, 0.920)	1.651(0.784, 3.588)	-3.302	< 0.001

脊髓损伤患者肠道菌群属水平的特征及意义

Characteristics of Genus-level Gut Microbiome in Patients with Spinal Cord Injury

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 5

参考文献 29

相关文章 15

Metrics

本文评价

推荐阅读 0

[1]	刘冬, 徐子涵, 李江, 鞠萍. M1区联合背外侧前额叶高频重复经颅磁刺激对脊髓损伤后神经病理性疼痛患者脑电图θ振幅的效果[J]. 《中国康复理论与实践》, 2024, 30(1): 87-94.
[2]	李芳, 霍速, 杜巨豹, 刘秀贞, 李小爽, 宋为群. 经颅直流电刺激联合任务导向性康复训练对脊髓损伤大鼠前肢运动障碍的效果[J]. 《中国康复理论与实践》, 2023, 29(7): 777-781.
[3]	刘宁, 刘雨泉, 祝斌, 于凌佳, 谭海宁, 杨雍, 李想. 脊髓损伤神经学分类国际标准国内应用情况的文献计量学研究[J]. 《中国康复理论与实践》, 2023, 29(7): 808-815.
[4]	王一吉, 周红俊, 何泽佳, 刘根林, 郑樱, 郝春霞, 卫波, 康海琼, 张缨, 逯晓蕾, 袁媛, 蒙倩茹. 不完全性脊髓损伤患者运动功能对称性与步态对称性的关系[J]. 《中国康复理论与实践》, 2023, 29(6): 639-645.
[5]	袁媛, 周红俊, 丛欣莹, 刘根林, 卫波, 郑樱, 郝春霞, 张缨, 王一吉, 康海琼, 逯晓蕾, 蒙倩茹. 创伤性颈脊髓损伤程度与磁共振成像的关系[J]. 《中国康复理论与实践》, 2023, 29(6): 725-730.
[6]	蒋乐, 杜良杰, 黄富表. 完全性脊髓损伤患者的情绪及认知行为分析[J]. 《中国康复理论与实践》, 2023, 29(5): 576-581.
[7]	郭霜, 谢咏祺, 张良, 张春佳, 彭润, 杨德刚, 杨明亮. 舞蹈致儿童无骨折脱位型脊髓损伤神经学预后的影响因素及预测模型[J]. 《中国康复理论与实践》, 2023, 29(5): 582-589.
[8]	张园, 杨剑. 基于ICD-11和ICF脊髓损伤患者运动康复干预方案及其健康效益：系统综述的系统综述[J]. 《中国康复理论与实践》, 2023, 29(12): 1377-1385.
[9]	石孝宇, 杨剑. 脊髓损伤患者适应性身体活动及其健康效益：基于ICF的Scoping综述[J]. 《中国康复理论与实践》, 2023, 29(12): 1395-1404.
[10]	刘根林,周红俊,李建军,卫波,郑樱,郝春霞,张缨,王一吉,康海琼,逯晓蕾,袁媛,蒙倩茹. 伴并发症脊髓损伤的神经学分类研究进展[J]. 《中国康复理论与实践》, 2022, 28(8): 934-938.
[11]	康海琼,周红俊,刘根林,卫波,郑樱,张缨,郝春霞,王一吉,逯晓蕾,袁媛,蒙倩茹. 脊髓损伤患者股骨远端和胫骨近端骨密度的变化[J]. 《中国康复理论与实践》, 2022, 28(7): 855-858.
[12]	张妙媛,何英,李晓霞,彭敏,张蕾,刘姝颖,孔瑛. 脊髓损伤清洁间歇导尿患者自我管理现状及影响因素[J]. 《中国康复理论与实践》, 2022, 28(6): 716-724.
[13]	周小珏,冯婧,庞日朝,刘捷,张安仁. 隔日限食减轻脊髓损伤大鼠炎症反应的芳香烃受体/细胞因子信号传导抑制因子2/核转录因子-κB信号通路机制[J]. 《中国康复理论与实践》, 2022, 28(5): 544-551.
[14]	魏娟芳,王琳杰,崔艳如,岑秋宇,张安仁. 骨髓间充质干细胞衍生外泌体对脊髓损伤动物治疗作用的系统综述[J]. 《中国康复理论与实践》, 2022, 28(5): 585-592.
[15]	栗亮,廖利民,吴娟,靖华芳,高轶,王越. 盆底肌训练对神经源性逼尿肌过度活动的效果[J]. 《中国康复理论与实践》, 2021, 27(9): 1093-1097.