干燥综合征与肠道菌群相关性研究进展
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摘要
肠道菌群在人体免疫系统中发挥着重要作用,肠道菌群及其代谢物的异常与一系列免疫性疾病密切相关。干燥综合征作为自身免疫性疾病的一种,其发病可能与多种因素相关。近年来的一系列研究提示肠道菌群通过调节肠道局部与全身免疫反应,会对干燥综合征的发生与发展产生重要影响。本文中笔者对干燥综合征患者的肠道菌群改变、肠道菌群对干燥综合征的影响及二者可能的免疫学联系进行阐述。
The gut microbiota plays a critical role in the human immune system,and abnormalities of the intestinal flora and its metabolites are closely related to a series of systemic autoimmune diseases.Sjgren's syndrome is one of the most common autoimmune disease whose onset may be relevant to a variety of factors. Over the recent years,emerging studies are suggesting that gut microbiota may be correlated with the occurrence or development of Sjgren's syndrome, through profoundly affecting the local and systemic immune responses. This review describes the gut microbiota changes in patients with Sjgren's syndrome,as well as itseffects on the disease and the possible immunological pathogenesis.
The gut microbiota plays a critical role in the human immune system,and abnormalities of the intestinal flora and its metabolites are closely related to a series of systemic autoimmune diseases.Sjgren's syndrome is one of the most common autoimmune disease whose onset may be relevant to a variety of factors. Over the recent years,emerging studies are suggesting that gut microbiota may be correlated with the occurrence or development of Sjgren's syndrome, through profoundly affecting the local and systemic immune responses. This review describes the gut microbiota changes in patients with Sjgren's syndrome,as well as itseffects on the disease and the possible immunological pathogenesis.
引文
[1]Zhong D,Wu C,Zeng X,et al.The role of gut microbiota in the pathogenesis of rheumatic diseases[J].Clin Rheumatol,2018,37(1):25-34.
[2]Clemente JC,Manasson J,Scher JU.The role of the gut microbiome in systemic inflammatory disease[J].Bmj,2018,360:j5145.
[3]Fox RI.Sjogren's syndrome[J].Lancet,2005,366(9482):321-331.
[4]中华医学会风湿病学分会.干燥综合征诊断及治疗指南[J].中华风湿病学杂志,2010,14(11):766-768.
[5]Vivino FB.Sjogren's syndrome:Clinical aspects[J].Clin Immunol,2017,182:48-54.
[6]Kuklinski E,Asbell PA.Sjogren's syndrome from the perspective of ophthalmology[J].Clin Immunol,2017,182:55-61.
[7]Tapinos NI,Polihronis M,Tzioufas AG,et al.Sjogren's syndrome Autoimmune epithelitis[J].Adv Exp Med Biol,1999,455:127-134.
[8]Goules AV,Kapsogeorgou EK,Tzioufas AG.Insight into pathogenesis of sjogren's syndrome:dissection on autoimmune infiltrates and epithelial cells[J].Clin Immunol,2017,182:30-40.
[9]Takeda K,Kaisho T,Akira S.Toll-like receptors[J].Annu Rev Immunol,2003,21:335-376.
[10]Jonsson R,Gordon TP,Konttinen YT.Recent advances in understanding molecular mechanisms in the pathogenesis and antibody profile of Sjogren's syndrome[J].Curr Rheumatol Rep,2003,5(4):311-316.
[11]Sawalha AH,Potts R,Schmid WR,et al.The genetics of primary Sjogren's syndrome[J].Curr Rheumatol Rep,2003,5(4):324-332.
[12]Tzioufas AG,Kapsogeorgou EK,Manoussakis MN,et al.Pathogenetic aspects of primary sj9gren's syndrome[M].London:Springer,2011:33-53.
[13]Kverka M,Tlaskalova-Hogenova H.Intestinal microbiota:facts and fiction[J].Dig Dis,2017,35(1-2):139-147.
[14]Rajilic-Stojanovic M,de Vos WM.The first 1000 cultured species of the human gastrointestinal microbiota[J].FEMSMicrobiol Rev,2014,38(5):996-1047.
[15]Koboziev I,Reinoso WC,Furr KL,et al.Role of the enteric microbiota in intestinal homeostasis and inflammation[J].Free Radic Biol Med,2014,68:122-133.
[16]Clooney AG,Fouhy F,Sleator RD,et al.Comparing apples and oranges?next generation sequencing and Its Impact on microbiome analysis[J].PLo S One,2016,11(2):e0148028.
[17]Bouskra D,Brezillon C,Berard M,et al.Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis[J].Nature,2008,456(7221):507-510.
[18]Moreau MC,Corthier G.Effect of the gastrointestinal microflora on induction and maintenance of oral tolerance to ovalbumin in C3H/He J mice[J].Infect Immun,1988,56(10):2766-2768.
[19]Pabst O,Herbrand H,Friedrichsen M,et al.Adaptation of solitary intestinal lymphoid tissue in response to microbiota and chemokine receptor CCR7 signaling[J].J Immunol,2006,177(10):6824-6832.
[20]Ivanov,I,Frutos Rde L,Manel N,et al.Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine[J].Cell Host Microbe,2008,4(4):337-349.
[21]Ivanov,I,Atarashi K,Manel N,et al.Induction of intestinal Th17 cells by segmented filamentous bacteria[J].Cell,2009,139(3):485-498.
[22]Geuking MB,Cahenzli J,Lawson MA,et al.Intestinal bacterial colonization induces mutualistic regulatory T cell responses[J].Immunity,2011,34(5):794-806.
[23]Fagarasan S,Kawamoto S,Kanagawa O,et al.Adaptive immune regulation in the gut:T cell-dependent and T cell-independent Ig A synthesis[J].Annu Rev Immunol,2010,28:243-273.
[24]Peterson DA,Mcnulty NP,Guruge JL,et al.Ig A response to symbiotic bacteria as a mediator of gut homeostasis[J].Cell Host Microbe,2007,2(5):328-339.
[25]Mora JR,Iwata M,Eksteen B,et al.Generation of gut-homing Ig A-secreting B cells by intestinal dendritic cells[J].Science,2006,314(5802):1157-1160.
[26]Sonnenberg GF,Artis D.Innate lymphoid cell interactions with microbiota:implications for intestinal health and disease[J].Immunity,2012,37(4):601-610.
[27]Fukuda S,Toh H,Hase K,et al.Bifidobacteria can protect from enteropathogenic infection through production of acetate[J].Nature,2011,469(7331):543-547.
[28]Petersson J,Schreiber O,Hansson GC,et al.Importance and regulation of the colonic mucus barrier in a mouse model of colitis[J].Am J Physiol Gastrointest Liver Physiol,2011,300(2):G327-G333.
[29]Fagundes CT,Amaral FA,Vieira AT,et al.Transient TLRactivation restores inflammatory response and ability to control pulmonary bacterial infection in germfree mice[J].J Immunol,2012,188(3):1411-1420.
[30]Kamada N,Seo SU,Chen GY,et al.Role of the gut microbiota in immunity and inflammatory disease[J].Nat Rev Immunol,2013,13(5):321-335.
[31]Hooper LV,Littman DR,Macpherson AJ.Interactions between the microbiota and the immune system[J].Science,2012,336(6086):1268-1273.
[32]Petersen C,Round JL.Defining dysbiosis and its influence on host immunity and disease[J].Cell Microbiol,2014,16(7):1024-1033.
[33]徐凤,张焕容,张兴民,等.不同年龄山羊胃肠道乳酸菌的分离鉴定[J].黑龙江畜牧兽医,2017(3):108-110.
[34]聂远洋,邓岳,刘戎梅,等.不同年龄麦洼牦牛肠道菌群的分离鉴定及其群落结构的变化[J].中国测试,2016,42(12):53-59.
[35]黄皓,郝丽,肖向红,等.肠道菌群功能及检测技术研究进展[J].黑龙江畜牧兽医,2018,61(13):48-51.
[36]郑艺,张家超,张和平.基于高通量测序技术分析肠道菌群及其影响因素的研究进展[J].中国食品学报,2014,14(11):157-164.
[37]钟海波,伍哓锋,曾瑜,等.多重耐药鲍曼不动杆菌ERIC-PCR的分子流行病学研究[J].现代医院,2013,13(12):19.
[38]Gnat S,Malek W,Olenska E,et al.Insight into the genomic diversity and relationship of Astragalus glycyphyllos symbionts by RAPD,ERIC-PCR,and AFLP fingerprinting[J].Journal of Applied Genetics,2015,56(4):551-554.
[39]Torriani S,Clementi F,Vancanneyt M,et al.Differentiation of Lactobacillus plantarum,L.pentosus and L.paraplantarum species by RAPD-PCR and AFLP[J].Systematic&Applied Microbiology,2001,24(4):554-558.
[40]Gueimonde M,Debor L,T9lkk9 S,et al.Quantitative assessment of faecal bifidobacterial populations by real-time PCRusing lanthanide probes[J].J Appl Microbiol,2007,102(4):1116-1122.
[41]Relman DA,Schmidt TM,Macdermott RP,et al.Identification of the uncultured bacillus of Whipple's disease[J].N Engl JMed,1992,327(5):293-297.
[42]Romano KA,Dillmcfarland KA,Kasahara K,et al.Fecal Aliquot Straw Technique(FAST)allows for easy and reproducible subsampling:assessing interpersonal variation in trimethylamine-N-oxide(TMAO)accumulation[J].Microbiome,2018,6(1):91-96.
[43]Nai C,Meyer V.From axenic to mixed cultures:technological advances accelerating a paradigm shift in microbiology[J].Trends Microbiol,2018,26(6):538-554.
[44]庄琪琛,宁芮之,麻远,等.微流控技术应用于细胞分析的研究进展[J].分析化学,2016,44(4):522-532.
[45]Chiron C,Tompkins TA,Burguière P.Flow cytometry:a versatile technology for specific quantification and viability assessment of microorganisms in multi-strain probiotic products[J].Journal of Applied Microbiology,2017:572-584.
[46]de Paiva CS,Jones DB,Stern ME,et al.Altered mucosal microbiome dversity and disease severity in sjogren syndrome[J].Sci Rep,2016,6:23561.
[47]Mandl T,Marsal J,Olsson P,et al.Severe intestinal dysbiosis is prevalent in primary Sjogren's syndrome and is associated with systemic disease activity[J].Arthritis Res Ther,2017,19(1):237.
[48]Furusawa Y,Obata Y,Fukuda S,et al.Commensal microbederived butyrate induces the differentiation of colonic regulatory Tcells[J].Nature,2013,504(7480):446-450.
[49]Miquel S,Martin R,Rossi O,et al.Faecalibacterium prausnitzii and human intestinal health[J].Curr Opin Microbiol,2013,16(3):255-261.
[50]Sharma R,Zheng L,Guo X,et al.Novel animal models for Sjogren's syndrome:expression and transfer of salivary gland dysfunction from regulatory T cell-deficient mice[J].JAutoimmun,2006,27(4):289-296.
[51]Szymula A,Rosenthal J,Szczerba BM,et al.T cell epitope mimicry between sjogren's syndrome antigen A(SSA)/Ro60 and oral,gut,skin and vaginal bacteria[J].Clin Immunol,2014,152(1-2):1-9.
[52]Wang C,Zaheer M,Bian F,et al.Sjogren-like lacrimal keratoconjunctivitis in germ-free mice[J].Int J Mol Sci,2018,19(2):565-569.
[53]Zaheer M,Wang C,Bian F,et al.Protective role of commensal bacteria in sjogren syndrome[J].J Autoimmun,2018,93:45-56.
[54]He B,Hoang TK,Wang T,et al.Resetting microbiota by lactobacillus reuteri inhibits T reg deficiency-induced autoimmunity via adenosine A2A receptors[J].J Exp Med,2017,214(1):107-123.
[55]Waidmann M,Bechtold O,Frick JS,et al.Bacteroides vulgatus protects against escherichia coli-induced colitis in gnotobiotic interleukin-2-deficient mice[J].Gastroenterology,2003,125(1):162-177.
[56]van der Meulen TA,Harmsen H,Bootsma H,et al.The microbiome-systemic diseases connection[J].Oral Dis,2016,22(8):719-734.
[2]Clemente JC,Manasson J,Scher JU.The role of the gut microbiome in systemic inflammatory disease[J].Bmj,2018,360:j5145.
[3]Fox RI.Sjogren's syndrome[J].Lancet,2005,366(9482):321-331.
[4]中华医学会风湿病学分会.干燥综合征诊断及治疗指南[J].中华风湿病学杂志,2010,14(11):766-768.
[5]Vivino FB.Sjogren's syndrome:Clinical aspects[J].Clin Immunol,2017,182:48-54.
[6]Kuklinski E,Asbell PA.Sjogren's syndrome from the perspective of ophthalmology[J].Clin Immunol,2017,182:55-61.
[7]Tapinos NI,Polihronis M,Tzioufas AG,et al.Sjogren's syndrome Autoimmune epithelitis[J].Adv Exp Med Biol,1999,455:127-134.
[8]Goules AV,Kapsogeorgou EK,Tzioufas AG.Insight into pathogenesis of sjogren's syndrome:dissection on autoimmune infiltrates and epithelial cells[J].Clin Immunol,2017,182:30-40.
[9]Takeda K,Kaisho T,Akira S.Toll-like receptors[J].Annu Rev Immunol,2003,21:335-376.
[10]Jonsson R,Gordon TP,Konttinen YT.Recent advances in understanding molecular mechanisms in the pathogenesis and antibody profile of Sjogren's syndrome[J].Curr Rheumatol Rep,2003,5(4):311-316.
[11]Sawalha AH,Potts R,Schmid WR,et al.The genetics of primary Sjogren's syndrome[J].Curr Rheumatol Rep,2003,5(4):324-332.
[12]Tzioufas AG,Kapsogeorgou EK,Manoussakis MN,et al.Pathogenetic aspects of primary sj9gren's syndrome[M].London:Springer,2011:33-53.
[13]Kverka M,Tlaskalova-Hogenova H.Intestinal microbiota:facts and fiction[J].Dig Dis,2017,35(1-2):139-147.
[14]Rajilic-Stojanovic M,de Vos WM.The first 1000 cultured species of the human gastrointestinal microbiota[J].FEMSMicrobiol Rev,2014,38(5):996-1047.
[15]Koboziev I,Reinoso WC,Furr KL,et al.Role of the enteric microbiota in intestinal homeostasis and inflammation[J].Free Radic Biol Med,2014,68:122-133.
[16]Clooney AG,Fouhy F,Sleator RD,et al.Comparing apples and oranges?next generation sequencing and Its Impact on microbiome analysis[J].PLo S One,2016,11(2):e0148028.
[17]Bouskra D,Brezillon C,Berard M,et al.Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis[J].Nature,2008,456(7221):507-510.
[18]Moreau MC,Corthier G.Effect of the gastrointestinal microflora on induction and maintenance of oral tolerance to ovalbumin in C3H/He J mice[J].Infect Immun,1988,56(10):2766-2768.
[19]Pabst O,Herbrand H,Friedrichsen M,et al.Adaptation of solitary intestinal lymphoid tissue in response to microbiota and chemokine receptor CCR7 signaling[J].J Immunol,2006,177(10):6824-6832.
[20]Ivanov,I,Frutos Rde L,Manel N,et al.Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine[J].Cell Host Microbe,2008,4(4):337-349.
[21]Ivanov,I,Atarashi K,Manel N,et al.Induction of intestinal Th17 cells by segmented filamentous bacteria[J].Cell,2009,139(3):485-498.
[22]Geuking MB,Cahenzli J,Lawson MA,et al.Intestinal bacterial colonization induces mutualistic regulatory T cell responses[J].Immunity,2011,34(5):794-806.
[23]Fagarasan S,Kawamoto S,Kanagawa O,et al.Adaptive immune regulation in the gut:T cell-dependent and T cell-independent Ig A synthesis[J].Annu Rev Immunol,2010,28:243-273.
[24]Peterson DA,Mcnulty NP,Guruge JL,et al.Ig A response to symbiotic bacteria as a mediator of gut homeostasis[J].Cell Host Microbe,2007,2(5):328-339.
[25]Mora JR,Iwata M,Eksteen B,et al.Generation of gut-homing Ig A-secreting B cells by intestinal dendritic cells[J].Science,2006,314(5802):1157-1160.
[26]Sonnenberg GF,Artis D.Innate lymphoid cell interactions with microbiota:implications for intestinal health and disease[J].Immunity,2012,37(4):601-610.
[27]Fukuda S,Toh H,Hase K,et al.Bifidobacteria can protect from enteropathogenic infection through production of acetate[J].Nature,2011,469(7331):543-547.
[28]Petersson J,Schreiber O,Hansson GC,et al.Importance and regulation of the colonic mucus barrier in a mouse model of colitis[J].Am J Physiol Gastrointest Liver Physiol,2011,300(2):G327-G333.
[29]Fagundes CT,Amaral FA,Vieira AT,et al.Transient TLRactivation restores inflammatory response and ability to control pulmonary bacterial infection in germfree mice[J].J Immunol,2012,188(3):1411-1420.
[30]Kamada N,Seo SU,Chen GY,et al.Role of the gut microbiota in immunity and inflammatory disease[J].Nat Rev Immunol,2013,13(5):321-335.
[31]Hooper LV,Littman DR,Macpherson AJ.Interactions between the microbiota and the immune system[J].Science,2012,336(6086):1268-1273.
[32]Petersen C,Round JL.Defining dysbiosis and its influence on host immunity and disease[J].Cell Microbiol,2014,16(7):1024-1033.
[33]徐凤,张焕容,张兴民,等.不同年龄山羊胃肠道乳酸菌的分离鉴定[J].黑龙江畜牧兽医,2017(3):108-110.
[34]聂远洋,邓岳,刘戎梅,等.不同年龄麦洼牦牛肠道菌群的分离鉴定及其群落结构的变化[J].中国测试,2016,42(12):53-59.
[35]黄皓,郝丽,肖向红,等.肠道菌群功能及检测技术研究进展[J].黑龙江畜牧兽医,2018,61(13):48-51.
[36]郑艺,张家超,张和平.基于高通量测序技术分析肠道菌群及其影响因素的研究进展[J].中国食品学报,2014,14(11):157-164.
[37]钟海波,伍哓锋,曾瑜,等.多重耐药鲍曼不动杆菌ERIC-PCR的分子流行病学研究[J].现代医院,2013,13(12):19.
[38]Gnat S,Malek W,Olenska E,et al.Insight into the genomic diversity and relationship of Astragalus glycyphyllos symbionts by RAPD,ERIC-PCR,and AFLP fingerprinting[J].Journal of Applied Genetics,2015,56(4):551-554.
[39]Torriani S,Clementi F,Vancanneyt M,et al.Differentiation of Lactobacillus plantarum,L.pentosus and L.paraplantarum species by RAPD-PCR and AFLP[J].Systematic&Applied Microbiology,2001,24(4):554-558.
[40]Gueimonde M,Debor L,T9lkk9 S,et al.Quantitative assessment of faecal bifidobacterial populations by real-time PCRusing lanthanide probes[J].J Appl Microbiol,2007,102(4):1116-1122.
[41]Relman DA,Schmidt TM,Macdermott RP,et al.Identification of the uncultured bacillus of Whipple's disease[J].N Engl JMed,1992,327(5):293-297.
[42]Romano KA,Dillmcfarland KA,Kasahara K,et al.Fecal Aliquot Straw Technique(FAST)allows for easy and reproducible subsampling:assessing interpersonal variation in trimethylamine-N-oxide(TMAO)accumulation[J].Microbiome,2018,6(1):91-96.
[43]Nai C,Meyer V.From axenic to mixed cultures:technological advances accelerating a paradigm shift in microbiology[J].Trends Microbiol,2018,26(6):538-554.
[44]庄琪琛,宁芮之,麻远,等.微流控技术应用于细胞分析的研究进展[J].分析化学,2016,44(4):522-532.
[45]Chiron C,Tompkins TA,Burguière P.Flow cytometry:a versatile technology for specific quantification and viability assessment of microorganisms in multi-strain probiotic products[J].Journal of Applied Microbiology,2017:572-584.
[46]de Paiva CS,Jones DB,Stern ME,et al.Altered mucosal microbiome dversity and disease severity in sjogren syndrome[J].Sci Rep,2016,6:23561.
[47]Mandl T,Marsal J,Olsson P,et al.Severe intestinal dysbiosis is prevalent in primary Sjogren's syndrome and is associated with systemic disease activity[J].Arthritis Res Ther,2017,19(1):237.
[48]Furusawa Y,Obata Y,Fukuda S,et al.Commensal microbederived butyrate induces the differentiation of colonic regulatory Tcells[J].Nature,2013,504(7480):446-450.
[49]Miquel S,Martin R,Rossi O,et al.Faecalibacterium prausnitzii and human intestinal health[J].Curr Opin Microbiol,2013,16(3):255-261.
[50]Sharma R,Zheng L,Guo X,et al.Novel animal models for Sjogren's syndrome:expression and transfer of salivary gland dysfunction from regulatory T cell-deficient mice[J].JAutoimmun,2006,27(4):289-296.
[51]Szymula A,Rosenthal J,Szczerba BM,et al.T cell epitope mimicry between sjogren's syndrome antigen A(SSA)/Ro60 and oral,gut,skin and vaginal bacteria[J].Clin Immunol,2014,152(1-2):1-9.
[52]Wang C,Zaheer M,Bian F,et al.Sjogren-like lacrimal keratoconjunctivitis in germ-free mice[J].Int J Mol Sci,2018,19(2):565-569.
[53]Zaheer M,Wang C,Bian F,et al.Protective role of commensal bacteria in sjogren syndrome[J].J Autoimmun,2018,93:45-56.
[54]He B,Hoang TK,Wang T,et al.Resetting microbiota by lactobacillus reuteri inhibits T reg deficiency-induced autoimmunity via adenosine A2A receptors[J].J Exp Med,2017,214(1):107-123.
[55]Waidmann M,Bechtold O,Frick JS,et al.Bacteroides vulgatus protects against escherichia coli-induced colitis in gnotobiotic interleukin-2-deficient mice[J].Gastroenterology,2003,125(1):162-177.
[56]van der Meulen TA,Harmsen H,Bootsma H,et al.The microbiome-systemic diseases connection[J].Oral Dis,2016,22(8):719-734.