肠道菌群失调引起类风湿关节炎发病的研究进展
|
摘要
肠道菌群大多与宿主共生进化,菌群结构、数量恒定形成稳态,能有效预防有害病菌的入侵和炎性疾病的发生。目前多项研究结果显示,肠道菌群失调可能与多种疾病相关联,包括2型糖尿病、肥胖症、肝硬化、结直肠癌和类风湿关节炎。有研究表明,肠道菌群是影响类风湿关节炎(rheumatoid arthritis, RA)发病的环境因素,其中涉及的机制有肠道菌群-黏膜稳态的失衡,其不利于肠道适应性免疫的形成,使得免疫系统不能识别常驻菌与致病菌,引起黏膜紊乱;另一种机制是肠道菌群失调激活免疫因子,引起全身免疫反应。由此可见,肠道菌群参与类风湿关节炎的发生、发展,既有肠道黏膜与菌群的局部调节,也有全身性免疫因子的共同参与。本文主要对肠道菌群失调诱导类风湿关节炎发病的相关性研究予以综述,为进一步研究关节炎早期预防及病因治疗提供理论依据。
Most of bacteria have co-evolved with the host in a symbiotic relationship. The structure and quantity of bacteria maintain homeostasis, which can effectively prevent the invasion of harmful bacteria and the occurrence of inflammatory diseases. A number of studies have shown that intestinal flora imbalance may be associated with a variety of diseases, including type 2 diabetes, obesity, cirrhosis, colorectal cancer and rheumatoid arthritis(RA). Studies have shown that intestinal flora is an environmental factor affecting the pathogenesis of RA, and one mechanism involved is the imbalance between intestinal flora and mucosal home-ostasis, which is not conducive to intestinal adaptive immunity. The formation of the immune system cannot identify resident and pathogenic bacteria, causing mucosal disorders. Another mechanism is that enteric dysbacteriosis will activate immune factors, causing systemic immune responses. Therefore, both local regu-lation of intestinal mucosa and flora and systemic immune factors participate in the occurrence and develop-ment of RA. Herein, the correlation between gut microbiota dysbiosis and RA was reviewed, which would provide a theoretical basis for further research on early prevention and etiological treatment of arthritis.
Most of bacteria have co-evolved with the host in a symbiotic relationship. The structure and quantity of bacteria maintain homeostasis, which can effectively prevent the invasion of harmful bacteria and the occurrence of inflammatory diseases. A number of studies have shown that intestinal flora imbalance may be associated with a variety of diseases, including type 2 diabetes, obesity, cirrhosis, colorectal cancer and rheumatoid arthritis(RA). Studies have shown that intestinal flora is an environmental factor affecting the pathogenesis of RA, and one mechanism involved is the imbalance between intestinal flora and mucosal home-ostasis, which is not conducive to intestinal adaptive immunity. The formation of the immune system cannot identify resident and pathogenic bacteria, causing mucosal disorders. Another mechanism is that enteric dysbacteriosis will activate immune factors, causing systemic immune responses. Therefore, both local regu-lation of intestinal mucosa and flora and systemic immune factors participate in the occurrence and develop-ment of RA. Herein, the correlation between gut microbiota dysbiosis and RA was reviewed, which would provide a theoretical basis for further research on early prevention and etiological treatment of arthritis.
引文
[1]李苗,孙迪,付冰冰,等.肠道菌群与自身免疫性疾病研究进展[J].中国微生态学杂志(LI Miao,SUN Di,FU Bing-bing,et al.Research on gut microbiota and autoimmune disease:progress review[J].Chinese Journal of Microecology),2015,27(10):1233-1237.
[2]ROSENBAUM J T,ASQUITH M J.The microbiome:a revolution in treatment for rheumatic diseases[J].Current Rheumatology Reports,2016,18:62.
[3]VAN DE WIELE T,VAN PRAET J T,MARZORATI M,et al.How the microbiota shapes rheumatic diseases[J].Nature Reviews Rheumatology,2016,12(7):398-411.
[4]MAEDA Y,KURAKAWA T,UMEMOTO E,et al.Dysbiosis contributes to arthritis development via activation of autoreac tive T cells in the intestine[J].Arthritis&Rheumatology,2016,68(11):2646-2661.
[5]CHEN J,WRIGHT K,DAVIS J M,et al.An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis[J].Genome Medicine,2016,8:43.
[6]ZHANG X,ZHANG D,JIA H,et al.The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment[J].Nature Medicine,2015,21(8):895-905.
[7]MARIETTA E V,MURRAY J A,LUCKEY D H,et al.Suppression of inflammatory arthritis by human gut-derived Prevotella histicola in humanized mice[J].Arthritis&Rheumatology,2016,68(12):2878-2888.
[8]COUTO N,SCHUELE L,RAANGS E C,et al.Critical steps in clinical shotgun metagenomics for the concomitant detection and typing of microbial pathogens[J].Scientific Reports,2018,8:13767.
[9]SCHROEDER B O,BACKHED F.Signals from the gut microbio ta to distant organs in physiology and disease[J].Nature Medicine,2016,22(10):1079-1089.
[10]KAMADA N,SEO S,CHEN G Y,et al.Role of the gut microbiota in immunity and inflammatory disease[J].Nature Reviews Immunology,2013,13(5):321-335.
[11]GOODRICH J K,DAVENPORT E R,BEAUMONT M,et al.Genetic determinants of the gut microbiome in UK twins[J].Cell Host&Microbe,2016,19(5):731-743.
[12]SCHER J U,SCZESNAK A,LONGMAN R S,et al.Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis[J].eLife,2013,2:e01202.
[13]刘晓飞,王志中,王勇,等.早期类风湿关节炎患者肠道微生物群落的分析[J].第三军医大学学报(LIU Xiao-fei,WANGZhi-zhong,WANG Yong,et al.Analysis of intestinal microbial community structure in patients with early rheumatoid arthritis[J].Journal of Third Military Medical University),2012,34(23):2411-2415.
[14]JUBAIR W K,HENDRICKSON J D,SEVERS E L,et al.Modulation of inflammatory arthritis in mice by gut microbiota through mucosal inflammation and autoantibody generation[J].Arthritis&Rheumatology,2018,70(8):1220-1233.
[15]RUSSELL M W,OGRA P L.Mucosal decisions:tolerance and responsiveness at mucosal surfaces[J].Immunological Investigations,2010,39(4-5):297-302.
[16]TLASKALOVA-HOGENOVAH,TU KOVAL,LODINOVA-ADNIKOVAR,et al.Mucosal immunity:its role in defense and allergy[J].International Archives of Allergy and Immunology,2002,128(2):77-89.
[17]CHUNG H,KASPER D L.Microbiota-stimulated immune mechanisms to maintain gut homeostasis[J].Current Opinion in Immunology,2010,22(4):455-460.
[18]GARRETT W S,GALLINI C A,YATSUNENKO T,et al.Enterobacteriaceae act in concert with the gut microbiota to in duce spontaneous and maternally transmitted colitis[J].Cell Host Microbe,2010,8(3):292-300.
[19]HILL D A,ARTIS D.Intestinal bacteria and the regulation of immune cell homeostasis[J].Annual Review of Immunology,2010,28:623-667.
[20]JANDHYALA S M,TALUKDAR R,SUBRAMANYAM C,et al.Role of the normal gut microbiota[J].World Journal of Gastroenterology,2015,21(29):8787-8803.
[21]谭迪.类风湿关节炎患者肠道菌群分析及致病菌筛选[D].大连:大连医科大学(Tan Di.Analysis of Intestinal Flora and Screening of Pathogenic Bacteria in Patients with Rheumatoid Arthritis[D].Dalian:Dalian Medical University),2018.
[22]LAFOREST-LAPOINTE I,ARRIETA M C.Patterns of early-life gut microbial colonization during human immune development:an ecological perspective[J].Frontisdaxers in Immunology,2017,8:788.
[23]BACKHED F,ROSWALL J,PENG Y,et al.Dynamics and stabilization of the human gut microbiome during the first year of life[J].Cell Host&Microbe,2015,17(5):690-703.
[24]SHREINER A B,KAO J Y,YOUNG V B.The gut microbiome in health and in disease[J].Current Opinion in Gastroenterology,2015,31(1):69-75.
[25]CHU H,MAZMANIAN S K.Innate immune recognition of the microbiota promotes host-microbial symbiosis[J].Nature Immunology,2013,14(7):668-675.
[26]ROUTY B,LE CHATELIER E,DEROSA L,et al.Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors[J].Science,2018,359(6371):91-97.
[27]LIU R,HONG J,XU X,et al.Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention[J].Nature Medicine,2017,23(7):859-868.
[28]TANEJA V.Arthritis susceptibility and the gut microbiome[J].FEBS Letters,2014,588(22):4244-4249.
[29]VERWOERD A,TER HAAR N M,DE ROOCK S,et al.The human microbiome and juvenile idiopathic arthritis[J].Pediatric Rheumatology,2016,14:55.
[30]JACKSON M A,GOODRICH J K,MAXAN M,et al.Proton pump inhibitors alter the composition of the gut microbiota[J].Gut,2016,65(5):749-756.
[31]FENG Q,LIANG S,JIA H,et al.Gut microbiome development along the colorectal adenoma carcinoma sequence[J].Nature Communications,2015,6:6528.
[32]ATARASHI K,TANOUE T,SHIMA T,et al.Induction of colonic regulatory T cells by indigenous Clostridium species[J].Science,2011,331(6015):337-341.
[33]TENG F,KLINGER C N,FELIX K M,et al.Gut microbiota drive autoimmune arthritis by promoting differentiation and migration of peyer’s patch T follicular helper cells[J].Immunity,2016,44(4):875-888.
[34]DENNING T L,WANG Y,PATEL S R,et al.Lamina propria macrophages and dendritic cells differentially induce regulato ry and interleukin 17 producing T cell responses[J].Nature Immunology,2007,8(10):1086-1094.
[35]KAMADA N,HISAMATSU T,OKAMOTO S,et al.Abnormally differentiated subsets of intestinal macrophage play a key role in Th1-dominant chronic colitis through excess produc tion of IL-12 and IL-23 in response to bacteria[J].The Journal of Immunology,2005,175(10):6900-6908.
[36]FRANCHI L,KAMADA N,NAKAMURA Y,et al.NLRC4-driven production of IL-1βdiscriminates between pathogenic and commensal bacteria and promotes host intestinal defense[J].Nature Immunology,2012,13(5):449-456.
[37]BORODY T J,KHORUTS A.Fecal microbiota transplantation and emerging applications[J].Nature Review Gastroenterol Hepatology,2011,9(2):88-96.
[2]ROSENBAUM J T,ASQUITH M J.The microbiome:a revolution in treatment for rheumatic diseases[J].Current Rheumatology Reports,2016,18:62.
[3]VAN DE WIELE T,VAN PRAET J T,MARZORATI M,et al.How the microbiota shapes rheumatic diseases[J].Nature Reviews Rheumatology,2016,12(7):398-411.
[4]MAEDA Y,KURAKAWA T,UMEMOTO E,et al.Dysbiosis contributes to arthritis development via activation of autoreac tive T cells in the intestine[J].Arthritis&Rheumatology,2016,68(11):2646-2661.
[5]CHEN J,WRIGHT K,DAVIS J M,et al.An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis[J].Genome Medicine,2016,8:43.
[6]ZHANG X,ZHANG D,JIA H,et al.The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment[J].Nature Medicine,2015,21(8):895-905.
[7]MARIETTA E V,MURRAY J A,LUCKEY D H,et al.Suppression of inflammatory arthritis by human gut-derived Prevotella histicola in humanized mice[J].Arthritis&Rheumatology,2016,68(12):2878-2888.
[8]COUTO N,SCHUELE L,RAANGS E C,et al.Critical steps in clinical shotgun metagenomics for the concomitant detection and typing of microbial pathogens[J].Scientific Reports,2018,8:13767.
[9]SCHROEDER B O,BACKHED F.Signals from the gut microbio ta to distant organs in physiology and disease[J].Nature Medicine,2016,22(10):1079-1089.
[10]KAMADA N,SEO S,CHEN G Y,et al.Role of the gut microbiota in immunity and inflammatory disease[J].Nature Reviews Immunology,2013,13(5):321-335.
[11]GOODRICH J K,DAVENPORT E R,BEAUMONT M,et al.Genetic determinants of the gut microbiome in UK twins[J].Cell Host&Microbe,2016,19(5):731-743.
[12]SCHER J U,SCZESNAK A,LONGMAN R S,et al.Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis[J].eLife,2013,2:e01202.
[13]刘晓飞,王志中,王勇,等.早期类风湿关节炎患者肠道微生物群落的分析[J].第三军医大学学报(LIU Xiao-fei,WANGZhi-zhong,WANG Yong,et al.Analysis of intestinal microbial community structure in patients with early rheumatoid arthritis[J].Journal of Third Military Medical University),2012,34(23):2411-2415.
[14]JUBAIR W K,HENDRICKSON J D,SEVERS E L,et al.Modulation of inflammatory arthritis in mice by gut microbiota through mucosal inflammation and autoantibody generation[J].Arthritis&Rheumatology,2018,70(8):1220-1233.
[15]RUSSELL M W,OGRA P L.Mucosal decisions:tolerance and responsiveness at mucosal surfaces[J].Immunological Investigations,2010,39(4-5):297-302.
[16]TLASKALOVA-HOGENOVAH,TU KOVAL,LODINOVA-ADNIKOVAR,et al.Mucosal immunity:its role in defense and allergy[J].International Archives of Allergy and Immunology,2002,128(2):77-89.
[17]CHUNG H,KASPER D L.Microbiota-stimulated immune mechanisms to maintain gut homeostasis[J].Current Opinion in Immunology,2010,22(4):455-460.
[18]GARRETT W S,GALLINI C A,YATSUNENKO T,et al.Enterobacteriaceae act in concert with the gut microbiota to in duce spontaneous and maternally transmitted colitis[J].Cell Host Microbe,2010,8(3):292-300.
[19]HILL D A,ARTIS D.Intestinal bacteria and the regulation of immune cell homeostasis[J].Annual Review of Immunology,2010,28:623-667.
[20]JANDHYALA S M,TALUKDAR R,SUBRAMANYAM C,et al.Role of the normal gut microbiota[J].World Journal of Gastroenterology,2015,21(29):8787-8803.
[21]谭迪.类风湿关节炎患者肠道菌群分析及致病菌筛选[D].大连:大连医科大学(Tan Di.Analysis of Intestinal Flora and Screening of Pathogenic Bacteria in Patients with Rheumatoid Arthritis[D].Dalian:Dalian Medical University),2018.
[22]LAFOREST-LAPOINTE I,ARRIETA M C.Patterns of early-life gut microbial colonization during human immune development:an ecological perspective[J].Frontisdaxers in Immunology,2017,8:788.
[23]BACKHED F,ROSWALL J,PENG Y,et al.Dynamics and stabilization of the human gut microbiome during the first year of life[J].Cell Host&Microbe,2015,17(5):690-703.
[24]SHREINER A B,KAO J Y,YOUNG V B.The gut microbiome in health and in disease[J].Current Opinion in Gastroenterology,2015,31(1):69-75.
[25]CHU H,MAZMANIAN S K.Innate immune recognition of the microbiota promotes host-microbial symbiosis[J].Nature Immunology,2013,14(7):668-675.
[26]ROUTY B,LE CHATELIER E,DEROSA L,et al.Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors[J].Science,2018,359(6371):91-97.
[27]LIU R,HONG J,XU X,et al.Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention[J].Nature Medicine,2017,23(7):859-868.
[28]TANEJA V.Arthritis susceptibility and the gut microbiome[J].FEBS Letters,2014,588(22):4244-4249.
[29]VERWOERD A,TER HAAR N M,DE ROOCK S,et al.The human microbiome and juvenile idiopathic arthritis[J].Pediatric Rheumatology,2016,14:55.
[30]JACKSON M A,GOODRICH J K,MAXAN M,et al.Proton pump inhibitors alter the composition of the gut microbiota[J].Gut,2016,65(5):749-756.
[31]FENG Q,LIANG S,JIA H,et al.Gut microbiome development along the colorectal adenoma carcinoma sequence[J].Nature Communications,2015,6:6528.
[32]ATARASHI K,TANOUE T,SHIMA T,et al.Induction of colonic regulatory T cells by indigenous Clostridium species[J].Science,2011,331(6015):337-341.
[33]TENG F,KLINGER C N,FELIX K M,et al.Gut microbiota drive autoimmune arthritis by promoting differentiation and migration of peyer’s patch T follicular helper cells[J].Immunity,2016,44(4):875-888.
[34]DENNING T L,WANG Y,PATEL S R,et al.Lamina propria macrophages and dendritic cells differentially induce regulato ry and interleukin 17 producing T cell responses[J].Nature Immunology,2007,8(10):1086-1094.
[35]KAMADA N,HISAMATSU T,OKAMOTO S,et al.Abnormally differentiated subsets of intestinal macrophage play a key role in Th1-dominant chronic colitis through excess produc tion of IL-12 and IL-23 in response to bacteria[J].The Journal of Immunology,2005,175(10):6900-6908.
[36]FRANCHI L,KAMADA N,NAKAMURA Y,et al.NLRC4-driven production of IL-1βdiscriminates between pathogenic and commensal bacteria and promotes host intestinal defense[J].Nature Immunology,2012,13(5):449-456.
[37]BORODY T J,KHORUTS A.Fecal microbiota transplantation and emerging applications[J].Nature Review Gastroenterol Hepatology,2011,9(2):88-96.