留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

高海拔地区藏族冠心病患者肠道菌群多态性研究

高中山 任明 马玉兰 朱露露

高中山, 任明, 马玉兰, 朱露露. 高海拔地区藏族冠心病患者肠道菌群多态性研究[J]. 协和医学杂志, 2022, 13(2): 332-340. doi: 10.12290/xhyxzz.2021-0652
引用本文: 高中山, 任明, 马玉兰, 朱露露. 高海拔地区藏族冠心病患者肠道菌群多态性研究[J]. 协和医学杂志, 2022, 13(2): 332-340. doi: 10.12290/xhyxzz.2021-0652
GAO Zhongshan, REN Ming, MA Yulan, ZHU Lulu. Polymorphism of Gut Microbiota in High Altitude Tibetan Patients with Coronary Artery Heart Disease[J]. Medical Journal of Peking Union Medical College Hospital, 2022, 13(2): 332-340. doi: 10.12290/xhyxzz.2021-0652
Citation: GAO Zhongshan, REN Ming, MA Yulan, ZHU Lulu. Polymorphism of Gut Microbiota in High Altitude Tibetan Patients with Coronary Artery Heart Disease[J]. Medical Journal of Peking Union Medical College Hospital, 2022, 13(2): 332-340. doi: 10.12290/xhyxzz.2021-0652

高海拔地区藏族冠心病患者肠道菌群多态性研究

doi: 10.12290/xhyxzz.2021-0652
基金项目: 

国家自然科学基金 81760084

青海省心血管疾病临床医学研究中心项目 2019-SF-L2

详细信息
    通讯作者:

    马玉兰,E-mail:mylfamai@163.com

  • 中图分类号: R543.3;R446.5

Polymorphism of Gut Microbiota in High Altitude Tibetan Patients with Coronary Artery Heart Disease

Funds: 

National Natural Science Foundation of China 81760084

Program of Qinghai Clinical Research Center for Cardiovascular Diseases 2019-SF-L2

More Information
  • 摘要:   目的  分析青藏高原藏族冠心病(coronary artery heart disease, CHD)患者肠道菌群的分布和组成特征。  方法  2018年9月至2020年9月, 连续招募世居青藏高原(海拔3600~4500 m)的藏族CHD患者[高海拔藏族CHD患者(high altitude Tibetan CHD, HTC)]和藏族健康人群[高海拔藏族健康人群(high altitude Tibetan normal, HTN)], 长期居住于西宁(海拔2260 m)的汉族CHD患者[中海拔汉族CHD患者(middle altitude Han CHD, MHC)]和武汉(海拔13 m)汉族CHD患者[低海拔汉族CHD患者(low altitude Han CHD, LHC)]。其中HTC与MHC均来自青海大学附属医院心内科住院患者, HTN均来自青海大学附属医院体检中心, LHC均来自华中科技大学附属协和医院心内科住院患者。收集研究对象粪便组织标本, 对肠道菌群16S rRNA V3~V4区进行DNA测序并进行生物信息学分析。  结果  共入选符合纳入和排除标准的CHD患者36例(HTC 8例、MHC 14例、LHC 14例), HTN 34例。α多样性分析显示, HTC与HTN的肠道菌群Shannon指数无显著性差异(P=0.091);HTC的肠道菌群Shannon指数最高, MHC次之, LHC最低(P=0.025)。β多样性分析显示, HTC的肠道菌群分布与HTN、MHC、LHC均存在显著差异。在对肠道菌群组成成分的分析中, HTC在门水平、属水平亦显示出不同于MHC、LHC的特征, 其致病菌如链球菌(Streptococcus)、埃希氏菌_志贺氏菌(Escherichia_Shigella)和克雷伯氏菌(Klebsiella)的相对丰度下降, 有益菌如粪杆菌(Faecalibacterium)、普氏菌(Prevotella)、链型杆菌(Catenibacterium)和乳酸杆菌(Lactobacillus)的相对丰度升高。  结论  高海拔藏族CHD患者肠道菌群呈现出不同于同海拔藏族健康人群以及中、低海拔CHD患者的多态性。
    作者贡献:高中山、任明、马玉兰进行研究构思与设计、可行性分析以及论文撰写与修订;高中山、朱露露进行标本、文献资料收集;马玉兰负责论文的质量控制及审校。
    利益声明:所有作者均声明不存在利益冲突
  • 图  1  高海拔藏族冠心病患者和高海拔藏族健康人群肠道菌群多样性比较

    A.稀疏曲线(Shannon指数);B. α多样性(Shannon指数);C. β多样性(主坐标分析);HTN、HTC: 同表 1;PCoA: 主坐标分析

    图  2  不同海拔、民族冠心病患者肠道菌群丰度和分布

    A. 稀疏曲线(Shannon指数);B.α多样性(Shannon指数);C. β多样性(主坐标分析);D. 基于加权UniFrac距离矩阵样本树树状图;HTC、MHC、LHC: 同表 1;PCoA: 同图 1

    图  3  不同海拔、民族冠心病患者肠道菌群在门水平上的组成差异

    A.肠道菌群优势菌门分布;B.FirmicutesBacteroidetes相对丰度比值;C~E.门水平肠道菌群组成差异;HTC、MHC、LHC: 同表 1;F/B: Firmicutes/Bacteroidetes

    图  4  不同海拔、民族冠心病患者肠道菌群属水平分布和组成差异

    A. 肠道菌群分布的LEfSe图;B.物种丰度热图示肠道菌群在属水平上的组成;HTC、MHC、LHC:同表 1

    表  1  患者一般临床资料比较

    指标 HTN(n=34) HTC(n=8) MHC(n=14) LHC(n=14) P
    年龄(x±s,岁) 52.4±6.5 57.6±9.7 58.4±12.1 54.9±8.3 0.130
    男性[n(%)] 23(67.6) 5(62.5) 10(62.5) 10(71.4) 0.968
    吸烟[n(%)] 8(23.5) 1(12.5) 8(57.1) 5(35.7) 0.084
    体质量指数(x±s,kg/m2) 23.7±4.5 24.4±1.9 23.9±1.2 25.1±2.1 0.606
    收缩压(x±s,mm Hg) 119.2±4.4 121.0±12.1 121.2±6.3 124.9±14.2 0.219
    舒张压(x±s,mm Hg) 76.5±6.3 75.1±5.8 78.6±5.4 75.6±7.8 0.540
    总胆固醇(x±s,mmol/L) 4.23±1.04 3.89±0.88 3.34±0.49* 3.30±0.89* 0.003
    甘油三酯(x±s,mmol/L) 1.52±0.73 1.92±0.66 1.58±0.57 1.54±0.68 0.510
    高密度脂蛋白胆固醇(x±s,mmol/L) 1.03±0.22 1.04±0.34 0.85±0.18 1.05±0.27 0.093
    低密度脂蛋白胆固醇(x±s,mmol/L) 2.82±0.94 2.10±0.94* 1.97±0.56* 1.84±0.79* 0.001
    HTC:高海拔藏族冠心病患者;HTN:高海拔藏族健康人群;MHC:中海拔汉族冠心病患者;LHC:低海拔汉族冠心病患者;*与HTN比较,差异具有统计学意义
    下载: 导出CSV
  • [1] Mingji C, Onakpoya IJ, Perera R, et al. Relationship between altitude and the prevalence of hypertension in Tibet: a systematic review[J]. Heart, 2015, 101: 1054-1060. doi:  10.1136/heartjnl-2014-307158
    [2] Faeh D, Gutzwiller F, Bopp M, et al. Lower mortality from coronary heart disease and stroke at higher altitudes in Switzerland[J]. Circulation, 2009, 120: 495-501. doi:  10.1161/CIRCULATIONAHA.108.819250
    [3] Fujimoto N, Matsubayashi K, Miyahara T, et al. The risk factors for ischemic heart disease in Tibetan highlanders[J]. Jpn Heart J, 1989, 30: 27-34. doi:  10.1536/ihj.30.27
    [4] 次仁罗布, 姜铁民, 金峰, 等. 西藏高海拔地区冠心病患者冠状动脉病变特点及其介入治疗疗效观察[J]. 世界最新医学信息文摘, 2018, 18: 13-18. https://www.cnki.com.cn/Article/CJFDTOTAL-WMIA201879006.htm
    [5] Tang WH, Kitai T, Kitai T, et al. Gut Microbiota in Cardiovascular Health and Disease[J]. Circ Res, 2017, 120: 1183-1196. doi:  10.1161/CIRCRESAHA.117.309715
    [6] Jia Z, Zhao X, Liu X, et al. Impacts of the Plateau Environment on the Gut Microbiota and Blood Clinical Indexes in Han and Tibetan Individuals[J]. mSystems, 2020, 5: 1-16.
    [7] Caporaso JG, Kuczynski J, Stombaugh J, et al. QⅡME allows analysis of high-throughput community sequencing data[J]. Nat Methods, 2010, 7: 335-336. doi:  10.1038/nmeth.f.303
    [8] Magoč T, Salzberg SL. FLASH: fast length adjustment of short reads to improve genome assemblies[J]. Bioinformatics, 2011, 27: 2957-2963. doi:  10.1093/bioinformatics/btr507
    [9] Edgar RC, Haas BJ, Clemente JC, et al. UCHIME improves sensitivity and speed of chimera detection[J]. Bioinformatics, 2011, 27: 2194-2200. doi:  10.1093/bioinformatics/btr381
    [10] Edgar RC. Search and clustering orders of magnitude faster than BLAST. Bioinformatics[J]. Bioinformatics, 2010, 26: 2460-2461. doi:  10.1093/bioinformatics/btq461
    [11] Quast C, Pruesse E, Yilmaz P, et al. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools[J]. Nucleic Acids Res, 2013, 41: 590-596.
    [12] Gasmi A, Mujawdiya PK, Pivina L, et al. Relationship between gut microbiota, gut hyperpermeability, and obesity[J]. Curr Med Chem, 2020, 27: 1-13. doi:  10.2174/092986732701200218105010
    [13] 胡海兵, 崔立, 郭靓骅, 等. 基于高通量测序技术的冠心病患者肠道菌群多样性研究[J]. 上海交通大学学报(农业科学版), 2016, 34: 1-19. https://www.cnki.com.cn/Article/CJFDTOTAL-SHNX201602001.htm
    [14] Arseneault-Bréard J, Rondeau I, Gilbert K, et al. Combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 reduces post-myocardial infarction depression symptoms and restores intestinal permeability in a rat model[J]. Br J Nutr, 2012, 107: 1793-1799. doi:  10.1017/S0007114511005137
    [15] Lam V, Su J, Koprowski S, et al. Intestinal microbiota determine severity of myocardial infarction in rats[J]. FASEB J, 2012, 26: 1727-1735. doi:  10.1096/fj.11-197921
    [16] Ott SJ, El Mokhtari NE, Musfeldt M, et al. Detection of diverse bacterial signatures in atherosclerotic lesions of patients with coronary heart disease[J]. Circulation, 2006, 113: 929-937. doi:  10.1161/CIRCULATIONAHA.105.579979
    [17] Koren O, Spor A, Felin J, et al. Human oral, gut, and plaque microbiota in patients with atherosclerosis[J]. Proc Natl ACHD Sci USA, 2011, 108: 4592-4598. doi:  10.1073/pnas.1011383107
    [18] Wu P, Chen JN, Chen JJ, et al. Trimethylamine N-oxide promotes apoE-/- mice atherosclerosis by inducing vascular endothelial cell pyroptosis via the SDHB/ROS pathway[J]. J Cell Physiol, 2020, 235: 6582-6591. doi:  10.1002/jcp.29518
    [19] 朱华, 李卓, 苏磊, 等. 冠心病人源肠道菌群小鼠模型的建立及评价[J]. 中国实验动物学报, 2019, 27: 716-724. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGSD201906004.htm
    [20] Zhu LL, Ma ZJ, Ren M, et al. Distinct Features of Gut Microbiota in High-Altitude Tibetan and Middle-Altitude Han Hypertensive Patients[J]. Cardiol Res Pract, 2020, 2020: 1957843.
    [21] Schneeberger M, Everard A, Gómez-Valadés AG, et al. Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice[J]. Sci Rep, 2015, 5: 16643. doi:  10.1038/srep16643
    [22] Ma Y, Zhu L, Ma Z, et al. Distinguishing feature of gut microbiota in Tibetan highland coronary artery disease patients and its link with diet[J]. Sci Rep, 2021, 11: 18486. doi:  10.1038/s41598-021-98075-9
    [23] Courtney HS, Pownall HJ. The structure and function of serum opacity factor: a unique streptococcal virulence determinant that targets high-density lipoproteins[J]. J Biomed Biotechnol, 2010, 2010: 956071.
    [24] Zhang B, Wang X, Xia R, et al. Gut microbiota in coronary artery disease: a friend or foe?[J]. Biosci Rep, 2020, 40: 1-11.
    [25] Li J, Zhao F, Wang Y, et al. Gut microbiota dysbiosis contributes to the development of hypertension[J]. Microbiome, 2017, 5: 14. doi:  10.1186/s40168-016-0222-x
    [26] Zhang M, Zhou L, Wang Y, et al. Faecalibacterium prausnitzii produces butyrate to decrease c-Myc-related metabolism and Th17 differentiation by inhibiting histone deacetylase 3[J]. Int Immunol, 2019, 31: 499-514. doi:  10.1093/intimm/dxz022
    [27] De Vadder F, Kovatcheva-Datchary P, Zitoun C, et al. Microbiota-Produced Succinate Improves Glucose Homeostasis via Intestinal Gluconeogenesis[J]. Cell Metab, 2016, 24: 151-157. doi:  10.1016/j.cmet.2016.06.013
    [28] Kelly TN, Bazzano LA, Ajami NJ, et al. Gut Microbiome Associates With Lifetime Cardiovascular Disease Risk Profile Among Bogalusa Heart Study Participants[J]. Circ Res, 2016, 1198: 956-964.
    [29] Park YE, Kim MS, Shim KW, et al. Effects of Lactobacillus plantarum Q180 on Postprandial Lipid Levels and Intestinal Environment: A Double-Blind, Randomized, Placebo-Controlled, Parallel Trial[J]. Nutrients, 2020, 12: 255. doi:  10.3390/nu12010255
    [30] Malik M, Suboc TM, Tyagi S, et al. Lactobacillus plantarum 299v Supplementation Improves Vascular Endothelial Function and Reduces Inflammatory Biomarkers in Men With Stable Coronary Artery Disease[J]. Circ Res, 2018, 123: 1091-1102. doi:  10.1161/CIRCRESAHA.118.313565
    [31] Gan XT, Ettinger G, Huang CX, et al. Probiotic administration attenuates myocardial hypertrophy and heart failure after myocardial infarction in the rat[J]. Circ Heart Fail, 2014, 7: 491-499. doi:  10.1161/CIRCHEARTFAILURE.113.000978
    [32] Liu H, Chen X, Hu X, et al. Alterations in the gut microbiome and metabolism with coronary artery disease severity[J]. Microbiome, 2019, 7: 68. doi:  10.1186/s40168-019-0683-9
  • 加载中
图(4) / 表(1)
计量
  • 文章访问数:  458
  • HTML全文浏览量:  92
  • PDF下载量:  18
  • 被引次数: 0
出版历程
  • 收稿日期:  2021-09-13
  • 录用日期:  2021-11-15
  • 网络出版日期:  2022-01-20
  • 刊出日期:  2022-03-30

目录

    /

    返回文章
    返回

    【温馨提醒】近日,《协和医学杂志》编辑部接到作者反映,有多名不法人员冒充期刊编辑发送见刊通知,鼓动作者添加微信,从而骗取版面费的行为。特提醒您,本刊与作者联系的方式均为邮件通知或电话,稿件进度通知邮箱为:mjpumch@126.com,编辑部电话为:010-69154261,请提高警惕,谨防上当受骗!如有任何疑问,请致电编辑部核实。谢谢!