肠道微生态失调与强直性脊柱炎发生发展的相关性分析
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摘要
强直性脊柱炎(ankylosing spondylitis,AS)发病较为隐蔽,机制复杂。目前临床诊断方法具有明显的滞后性,因此寻求更为快速、准确的早期诊断指标对缓解甚至治愈AS显得极为重要。现有的大量研究显示肠道微生物与AS关系密切,且可能通过肠道微生物与遗传因子HLA-B27相互作用、肠道通透性改变介导的肠黏膜IgA免疫应答和炎性因子的过度表达、肠-脑轴、肠道微生物之间的相互作用等机制导致AS的发生发展。本文就AS患者肠道微生物变化及肠道微生态失调与AS的相关性作一综述。
The onset of ankylosing spondylitis(AS)is concealed and complicated.The current clinical diagnosis method is obviously lack of timeliness,so it′s very important to look for a more rapid and accurate early diagnosis index in order to relieve or even cure AS.A large number of existing researches showed that the gut microbiota is closely related to AS,and may lead to the development of AS through different mechanisms such as the interaction between gut microbiota and genetic factor HLA-B27,intestinal mucosal IgA immune response and inflammatory factor overexpression mediated by intestinal permeability changes,the interaction between brain-gut axis and intestinal microbes,and so on.This article reviews the changes of intestinal microflora in patients with AS,and the possible correlation between AS and intestinal microecology.
The onset of ankylosing spondylitis(AS)is concealed and complicated.The current clinical diagnosis method is obviously lack of timeliness,so it′s very important to look for a more rapid and accurate early diagnosis index in order to relieve or even cure AS.A large number of existing researches showed that the gut microbiota is closely related to AS,and may lead to the development of AS through different mechanisms such as the interaction between gut microbiota and genetic factor HLA-B27,intestinal mucosal IgA immune response and inflammatory factor overexpression mediated by intestinal permeability changes,the interaction between brain-gut axis and intestinal microbes,and so on.This article reviews the changes of intestinal microflora in patients with AS,and the possible correlation between AS and intestinal microecology.
引文
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[37]何伟珍,李剑松,叶志中,等.强直性脊柱炎患者泛素mRNA的表达及意义[J].广东医学,2009,30(2):215-216.
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[44]Ebringer A,Wilson C.The use of a low starch diet in the treatment of patients suffering from ankylosing spondylitis[J].Clin Rheumatol,1996,15(1):62-66.
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[2]Wen C,Zheng Z,Shao T,et al.Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis[J].Genome Biol,2017,18(1):142.
[3]TAN Xi,XU Yongyue,QIU Dongni,et al.Research progress of classification and pathogenesis in ankylosing spondylitis animal models[J].Chin J Tissue Engin Res,2017,21(11):1783-1789.(in Chinese)谭希,徐永跃,邱冬妮,等.强直性脊柱炎动物模型归类及其机制研究与进展[J].中国组织工程研究,2017,21(11):1783-1789.
[4]Zhai J,Rong J,Li Q,et al.Immunogenetic study in Chinese population with ankylosing spondylitis:Are there specific genes recently disclosed?[J].Clin Dev Immunol,2013:419357.
[5]Bremander A,Petersson I F,Bergman S,et al.Populationbased estimates of common comorbidities and cardiovascular disease in ankylosing spondylitis[J].Arthritis Care Res(Hoboken),2011,63(4):550-556.
[6]Robinson PC,Leo PJ,Pointon JJ,et al.Exome-wide study of ankylosing spondylitis demonstrates additional shared genetic background with inflammatory bowel disease[J].NPJ Genom Med.2016,1:16008.
[7]Costello M,Ciccia F,Willner D,et al.Brief report:Intestinal dysbiosis in ankylosing spondylitis[J].Arthritis Rheumatol,2015,67(3):686-691.
[8]Bowel flora and ankylosing spondylitis[J].Lancet,1986,2(8518):1259.
[9]Collins SM.A role for the gut microbiota in IBS[J].Nat Rev Gastroenterol Hepatol,2014,11(8):497-505.
[10]Qin J,Li R,Raes J,et al.A human gut microbial gene catalogue established by metagenomic sequencing[J].Nature,2010,464(7285):59-65.
[11]HUANG Xiuyan,ZENG Yaoying.Advances in pathophysiology of gut microbiota[J].Chin J Pathophysiol,2014,30(6):1127-1135.(in Chinese)黄秀艳,曾耀英.肠道微生物群的病理生理学进展[J].中国病理生理杂志,2014,30(6):1127-1135.
[12]Frey-Klett P,Burlinson P,Deveau A,et al.Bacterial-fungal interactions:Hyphens between agricultural,clinical,environmental,and food microbiologists[J].Microbiol Mol Biol Rev,2011,75(4):583-609.
[13]JIN Hongzhi,LI Kunbao.Progress in the study of human intestinal microecosystem[J].Nat Magaz,2004,26(2):88-91.(in Chinese)金红芝,李堃宝.人肠道微生态系统的研究进展[J].自然杂志,2004,26(2):88-91.
[14]Ott SJ,Kühbacher T,Musfeldt M,et al.Fungi and inflammatory bowel diseases:Alterations of composition and diversity[J].Scand J Gastroenterol,2008,43(7):831-841.
[15]Scupham AJ,Presley LL,Wei B,et al.Abundant and diverse fungal microbiota in the murine intestine[J].Appl Environl Microbiol,2006,72(1):793-801.
[16]Sokol H,Leducq V,Aschard H,et al.Fungal microbiota dysbiosis in IBD[J].Gut,2017,66(6):1039-1048.
[17]刘毅,蔡醒华.肠道炎症及细菌感染在强直性脊柱炎发病中的作用[J].中华内科杂志,1995,34(5):337-338.
[18]杨清锐,遇晓,张源潮,等.强直性脊柱炎的治疗[J].山东医药,2001,41(9):57-58.
[19]Rath HC,Wilson KH,Sartor RB.Differential induction of colitis and gastritis in HLA-B27transgenic rats selectively colonized with Bacteroides vulgatus or Escherichia coli[J].Infect Immun,1999,67(6):2969-2974.
[20]Stone MA,Payne U,Schentag C,et al.Comparative immune responses to candidate arthritogenic bacteria do not confirm a dominant role for Klebsiella pneumoniain the pathogenesis of familial ankylosing spondylitis[J].Rheumatology(Oxford),2004,43(2):148-155.
[21]Gill T,Asquith M,Rosenbaum JT,et al.The intestinal microbiome in spondyloarthritis[J].Curr Opin Rheumatol,2015,27(4):319-325.
[22]Stebbings S,Munro K,Simon MA,et al.Comparison of the faecal microflora of patients with ankylosing spondylitis and controls using molecular methods of analysis[J].Rheumatology(Oxford),2002,41(12):1395-1401.
[23]ZHANG Lilong,XU Yao,HU Yuqi,et al.Characteristics of the intestinal fungal microbiota in patients with ankylosing spondylitis based on ITS2 high-throughput sequencing[J].Chin J Microecol,2018(2):125-131.(in Chinese)张利龙,许尧,胡雨奇,等.基于ITS2高通量测序研究强直性脊柱炎患者肠道真菌特征[J].中国微生态学杂志,2018,30(2):125-131.
[24]曹雪涛.医学免疫学[M].6版.北京:人民卫生出版社,2013:73.
[25]王吉耀,廖二元,胡品津.内科学[M].北京:人民卫生出版社,2005:7.
[26]Krimpenfort P,Rudenko G,Hochstenbach F,et al.Crosses of two independently derived transgenic mice demonstrate functional complementation of the genes encoding heavy(HLAB27)and light(beta 2-microglobulin)chains of HLA class I antigens[J].EMBO J,1987,6(6):1673-1676.
[27]Taurog JD,Maika SD,Satumtira N,et al.Inflammatory disease in HLA-B27transgenic rats[J].Immunol Rev,1999,169(1):209.
[28]Rath HC,Herfarth HH,Ikeda JS,et al.Normal luminal bacteria,especially Bacteroides species,mediate chronic colitis,gastritis,and arthritis in HLA-B27/human beta2microglobulin transgenic rats[J].J Clin Invest,1996,98(4):945-953.
[29]Taurog JD,Richardson JA,Croft JT,et al.The germfree state prevents development of gut and joint inflammatory disease in HLA-B27transgenic rats[J].J Exp Med,1994,180(6):2359-2364.
[30]Rosenbaum JT,Davey MP.Time for a gut check:Evidence for the hypothesis that HLA-B27predisposes to ankylosing spondylitis by altering the microbiome[J].Arthritis Rheum,2011,63(11):3195-3198.
[31]Ebringer A,Ghuloom M.Ankylosing spondylitis,HLA-B27,and klebsiella:Cross reactivity and antibody studies[J].Ann Rheum Dis,1986,45(8):703-704.
[32]Rashid T,Ebringer A.Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry[J].Autoimmune Dis,2012:539282.
[33]冯媛.HLA-B27启动子活性及启动子激活因子参与脊柱关节病发病机制的研究[D].西安:第四军医大学,2009.
[34]Evans DM,Spencer CC,Pointon JJ,et al.Interaction between ERAP1and HLA-B27in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27in disease susceptibility[J].Nat Genet,2011,43(8):761-767.
[35]YAN Dong,CUI Xingzheng,JI Wenzhong,et al.Expression and significance of unfolded protein response related factors(GRP78,ATF6and XPB1)in human esophageal squamous cell carcinoma[J].J Diag Pathol,2014,21(5):293-296.(in Chinese)闫东,崔新征,吉文仲,等.未折叠蛋白反应相关因子GRP78、ATF6和XPB1在人食管鳞状细胞癌中的表达及其意义[J].诊断病理学杂志,2014,21(5):293-296.
[36]SUI Cong,BU Haifu.Advances in research of pathogenesis and treatment of ankylosing spondylitis[J].J Clin Orthop,2010,13(2):217-22.(in Chinese)隋聪,卜海富.强直性脊柱炎发病机制与治疗的研究进展[J].临床骨科杂志,2010,13(2):217-220.
[37]何伟珍,李剑松,叶志中,等.强直性脊柱炎患者泛素mRNA的表达及意义[J].广东医学,2009,30(2):215-216.
[38]Ciccia F,Accardo-Palumbo A,Rizzo A,et al.Evidence that autophagy,but not the unfolded protein response,regulates the expression of IL-23in the gut of patients with ankylosing spondylitis and subclinical gut inflammation[J].Ann Rheum Dis,2014,73(8):1566.
[39]Mkiikola O,NissilM,Lehtinen K,et al.IgA class serum antibodies against three different Klebsiella serotypes in ankylosing spondylitis[J].Br J Rheumatol,1998,37(12):1299-1302.
[40]吴启富,姚中强,肖长虹,等.肠道通透性与强直性脊柱炎发病机制相关性研究[C]//吴启富、叶志中.全国中西医结合强直性脊柱炎专题研讨会论文汇编,深圳,2007:112.
[41]Mielants H,De Vos M,Goemaere S,et al.Intestinal mucosal permeability in inflammatory rheumatic diseases.II.Role of disease[J].J Rheumatol,1991,18(3):394-400.
[42]Atarashi K,Honda K.Microbiota in autoimmunity and tolerance[J].Curr Opin Immunol,2011,23(6):761-768.
[43]丁轲,余祖华,王天奇.肠道黏膜免疫研究进展[J].动物医学进展,2007,28(10):67-71.
[44]Ebringer A,Wilson C.The use of a low starch diet in the treatment of patients suffering from ankylosing spondylitis[J].Clin Rheumatol,1996,15(1):62-66.
[45]Akira S,Takeda K,Kaisho T.Toll-like receptors:Critical proteins linking innate and acquired immunity[J].Nat Immunol,2001,2(8):675-680.
[46]YANG Zaixing,LIANG Yan,ZENG Xianming,et al.Analysis for expression of TLR4on leucocytes from patients with ankylosing spondylitis and its clinical significanc[J].Chin J Clin Lab Sci,2007,25(4):293-294.(in Chinese)杨再兴,梁艳,曾贤铭,等.Toll样受体4在强直性脊柱炎患者外周血白细胞中的表达及临床意义初探[J].临床检验杂志,2007,25(4):293-294.
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