肠道菌群在自身免疫性甲状腺疾病中的研究进展
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摘要
肠道菌群在人体健康中发挥至关重要的作用,当菌群稳态受损导致上皮屏障功能障碍时会引发肠道及全身疾病。自身免疫性甲状腺疾病是一种器官特异性自身免疫病,病因和发病机制尚未完全阐明,这意味着自身免疫性甲状腺疾病的治疗存在局限性,并且不能预防以及进行早期疾病诊断。肠道微生物可能在自身免疫性甲状腺疾病的发病机制中发挥重要作用,并且自身免疫性甲状腺疾病患者肠道微生物的丰度与多样性均发生明显改变,这些证据可能为自身免疫性甲状腺疾病的治疗提供新的方式。
Intestinal microbiota is of great significance for human health,and intestinal and systemic diseases may be triggered due to epithelial barrier dysfunction caused by its imbalance. Autoimmune thyroid disease,an organ specific autoimmune disease,is still lack of treatment methods,early diagnosis and preventive present because the etiology and pathogenesis are still not fully elaborated. However,it is supposed that intestinal microbiota may play an important role in the pathogenesis of autoimmune thyroid,and these patients had significant changes in abundance and diversity of intestinal microbiota. Thus,these studies may provide new therapies for autoimmune thyroid.
Intestinal microbiota is of great significance for human health,and intestinal and systemic diseases may be triggered due to epithelial barrier dysfunction caused by its imbalance. Autoimmune thyroid disease,an organ specific autoimmune disease,is still lack of treatment methods,early diagnosis and preventive present because the etiology and pathogenesis are still not fully elaborated. However,it is supposed that intestinal microbiota may play an important role in the pathogenesis of autoimmune thyroid,and these patients had significant changes in abundance and diversity of intestinal microbiota. Thus,these studies may provide new therapies for autoimmune thyroid.
引文
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[14]Rajili-Stojanovi M,de Vos WM.The first 1000 cultured species of the human gastrointestinal microbiota[J].FEMS Microbiol Rev,2014,38(5):996-1047.
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[16]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.
[17]Zhang X,Zhang D,Jia H,et al.The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment[J].Nat Med,2015,21(8):895-905.
[18]Wilck N,Matus MG,Kearney SM,et al.Salt-responsive gut commensal modulates TH17 axis and disease[J].Nature,2017,551(7682):585-589.
[19]Qin J,Li Y,Cai Z,et al.A metagenome-wide association study of gut microbiota in type 2 diabetes[J].Nature,2012,490(7418):55-60.
[20]Zhao L.The gut microbiota and obesity:From correlation to causality[J].Nat Rev Microbiol,2013,11(9):639-647.
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[25]Virili C,Fallahi P,Antonelli A,et al.Gut microbiota and Hashimoto's thyroiditis[J].Rev Endocr Metab Disord,2018,19(4):293-300.
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[30]Scher JU,Bretz WA,Abramson SB.Periodontal disease and subgingival microbiota as contributors for rheumatoid arthritis pathogenesis:Modifiable risk factors?[J].Curr Opin Rheumatol,2014,26(4):424-429.
[31]Verma R,Verma AK,Ahuja V,et al.Real-time analysis of mucosal flora in patients with inflammatory bowel disease in India[J].J Clin Microbiol,2010,48(11):4279-4282.
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[34]Chen J,Chia N,Kalari KR,et al.Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls[J].Sci Rep,2016,6:28484.
[35]Kang DW,Park JG,Ilhan ZE,et al.Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children[J].PLo S One,2013,8(7):e68322.
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[42]Rajili stojanovi M,Biagi E,Heilig HG,et al.Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome[J].Gastroenterology,2011,141(5):1792-1801.
[43]Jeffery IB,O'Toole PW,Ohman L,et al.An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota[J].Gut,2012,61(7):997-1006.
[44]Penhale WJ,Young PR.The influence of the normal microbial flora on the susceptibility of rats to experimental autoimmune thyroidi tis[J].Clin Exp Immunol,1988,72(2):288-292.
[45]Burek CL,Talor MV.Environmental triggers of autoimmune thyroiditis[J].J Autoimmun,2009,33(3/4):183-189.
[46]Horie I,Abiru N,Nagayama Y,et al.T helper type 17 immune response plays an indispensable role for development of iodineinduced autoimmune thyroiditis in nonobese diabetic-H2h4 mice[J].Endocrinology,2009,150(11):5135-1542.
[47]Yu S,Maiti PK,Dyson M,et al.B cell-deficient NOD.H-2h4mice have CD4+CD25+T regulatory cells that inhibit the development of spontaneous autoimmune thyroiditis[J].J Exp Med,2006,203(2):349-258.
[48]Moshkelgosha S,Masetti G,Berchner-Pfannschmidt U,et al.Gut Microbiome in BALB/c and C57BL/6J Mice Undergoing Experimental Thyroid Autoimmunity Associate with Differences in Immunological Responses and Thyroid Function[J].Horm Metab Res,2018,50(12):932-941.
[49]Masetti G,Moshkelgosha S,Kohling HL,et al.Gut microbiota in experimental murine model of Graves'orbitopathy established in different environments may modulate clinical presentation of disease[J].Microbiome,2018,6(1):97.
[50]Goldberg EA,Venkat-Ramani T,Hewit M,et al.Epidemiology and clinical outcomes of patients with Fusobacterium bacteraemia[J].Epidemiol Infect,2013,141(2):325-329.
[51]Kostic AD,Gevers D,Pedamallu CS,et al.Genomic analysis identifies association of Fusobacterium with colorectal carcinoma[J].Genome Res,2012,22(2):292-298.
[52]Mccoy AN,Araújo-Pérez F,Azcárate-Peril A,et al.Fusobacterium is associated with colorectal adenomas[J].PLo S One,2013,8(1):e53653.
[53]He Z,Shao T,Li H,et al.Alterations of the gut microbiome in Chinese patients with systemic lupus erythematosus[J].Gut Pathog,2016,8(1):64.
[54]Huang F,Qiao HM,Yin JN,et al.Early-life exposure to clostridium leptum causes pulmonary immunosuppression[J].PLo S One,2015,10(11):e0141717.
[55]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.
[2]Chen C,Xu H,Chen Y,et al.Iodized salt intake and its association with urinary iodine,TPOAb and Tg Ab among urban Chinese[J].Thyroid,2017,27(12):1566-1573.
[3]Li L,Ding X,Wang X,et al.Polymorphisms of IKZF3 gene and autoimmune thyroid diseases:Associated with Graves'disease but not with Hashimoto's thyroiditis[J].Cell Physiol Biochem,2018,45(5):1787-1796.
[4]Guo Q,Wu D,Yu H,et al.Alterations of global DNA methylation and DNMT expression in T and B lymphocytes from patients with newly diagnosed AITD after treatment:A follow-up study[J].Thyroid,2018,28(3):377-385.
[5]Li Q,Ye H,Ding Y,et al.Clinical characteristics of moderate-tosevere thyroid associated ophthalmopathy in 354 Chinese cases[J].PLo S One,2017,12(5):e0176064.
[6]Jia M,Shi X,Gu X,et al.Smoking is positively associated with antithyroperoxidase antibodies and antithyroglobulin antibodies in populations with mildly deficient iodine intake[J].Biol Trace Elem Res,2018(8):383-391.
[7]Hajishengallis G.The inflammophilic character of the periodontitis-associated microbiota[J].Mol Oral Microbiol,2015,29(6):248-257.
[8]Scher JU,Ubeda C,Artacho A,et al.Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis,resembling dysbiosis in inflammatory bowel disease[J].Arthritis Rheumatol,2015,67(1):128-139.
[9]Brusca SB,Abramson SB,Scher JU.Microbiome and mucosal inflammation as extra-articular triggers for rheumatoid arthritis and autoimmunity[J].Curr Opin Rheumatol,2014,26(1):101-107.
[10]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.
[11]Costello ME,Ciccia F,Willner D,et al.Brief report:Intestinal dysbiosis in ankylosing spondylitis[J].Arthritis Rheumatol,2015,67(3):686-691.
[12]郑鹏,嵇武.肠道菌群与肠道疾病的研究进展[J].医学综述,2014,20(24):4479-4481.
[13]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.
[14]Rajili-Stojanovi M,de Vos WM.The first 1000 cultured species of the human gastrointestinal microbiota[J].FEMS Microbiol Rev,2014,38(5):996-1047.
[15]Nicholson JK,Holmes E,Kinross J,et al.Host-gut microbiota metabolic interactions[J].Science,2012,336(6086):1262-1267.
[16]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.
[17]Zhang X,Zhang D,Jia H,et al.The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment[J].Nat Med,2015,21(8):895-905.
[18]Wilck N,Matus MG,Kearney SM,et al.Salt-responsive gut commensal modulates TH17 axis and disease[J].Nature,2017,551(7682):585-589.
[19]Qin J,Li Y,Cai Z,et al.A metagenome-wide association study of gut microbiota in type 2 diabetes[J].Nature,2012,490(7418):55-60.
[20]Zhao L.The gut microbiota and obesity:From correlation to causality[J].Nat Rev Microbiol,2013,11(9):639-647.
[21]Zhao F,Feng J,Li J,et al.Alterations of the gut microbiota in Hashimoto's thyroiditis patients[J].Thyroid,2018,28(2):175-186.
[22]Ishaq HM,Mohammad IS,Guo H,et al.Molecular estimation of alteration in intestinal microbial composition in Hashimoto's thyroiditis patients[J].Biomed Pharmacother,2017,95:865-874.
[23]Zhou L,Li X,Ahmed A,et al.Gut microbe analysis between hyperthyroid and healthy individuals[J].Curr Microbiol,2014,69(5):675-680.
[24]Ishaq HM,Mohammad IS,Shahzad M,et al.Molecular alteration analysis of human gut microbial composition in Graves'disease patients[J].Int J Biol Sci,2018,14(11):1558-1570.
[25]Virili C,Fallahi P,Antonelli A,et al.Gut microbiota and Hashimoto's thyroiditis[J].Rev Endocr Metab Disord,2018,19(4):293-300.
[26]Benvenga S,Guarneri F.Molecular mimicry and autoimmune thyroid disease[J].Rev Endocr Metab Disord,2016,17(4):485-498.
[27]Kiseleva EP,Mikhailopulo KI,Sviridov OV,et al.The role of components of bifidobacterium and lactobacillus in pathogenesis and serologic diagnosis of autoimmune thyroid diseases[J].Benef Microbes,2011,2(2):139-154.
[28]Lv LX,Fang DQ,Shi D,et al.Alterations and correlations of the gut microbiome,metabolism and immunity in patients with primary biliary cirrhosis[J].Environ Microbiol,2016,18(7):2272-2286.
[29]Lynch SV,Pedersen O.The human intestinal microbiome in health and disease[J].N Engl J Med,2016,375(24):2369-2379.
[30]Scher JU,Bretz WA,Abramson SB.Periodontal disease and subgingival microbiota as contributors for rheumatoid arthritis pathogenesis:Modifiable risk factors?[J].Curr Opin Rheumatol,2014,26(4):424-429.
[31]Verma R,Verma AK,Ahuja V,et al.Real-time analysis of mucosal flora in patients with inflammatory bowel disease in India[J].J Clin Microbiol,2010,48(11):4279-4282.
[32]Murri M,Leiva I,Gomez-Zumaquero JM,et al.Gut microbiota in children with type 1 diabetes differs from that in healthy children:A case-control study[J].BMC Med,2013,11(1):46.
[33]Armougom F,Henry M,Vialettes B,et al.Monitoring bacterial community of human gut microbiota reveals an increase in Lactobacillus in obese patients and Methanogens in anorexic patients[J].PLo S One,2009,4(9):e7125.
[34]Chen J,Chia N,Kalari KR,et al.Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls[J].Sci Rep,2016,6:28484.
[35]Kang DW,Park JG,Ilhan ZE,et al.Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children[J].PLo S One,2013,8(7):e68322.
[36]De Filippis F,Vannini L,La Storia A,et al.The same microbiota and a potentially discriminant metabolome in the saliva of omnivore,ovo-lacto-vegetarian and Vegan individuals[J].PLo S One,2014,9(11):e112373.
[37]Amani J,Ahmadpour A,Imani Fooladi AA,et al.Detection of E.coli O157:H7 and Shigella dysenteriae toxins in clinical samples by PCR-ELISA[J].Braz J Infect Dis,2015,19(3):278-284.
[38]Kverka M,Zakostelska Z,Klimesova K,et al.Oral administration of Parabacteroides distasonis antigens attenuates experimental murine colitis through modulation of immunity and microbiota composition[J].Clin Exp Immunol,2011,163(2):250-259.
[39]Takeshita K,Mizuno S,Mikami Y,et al.A single species of clostridium subcluster XIVa decreased in ulcerative colitis patients[J].Inflamm Bowel Dis,2016,22(12):2802-2810.
[40]Krogius-Kurikka L,Lyra A,Malinen E,et al.Microbial community analysis reveals high level phylogenetic alterations in the overall gastrointestinal microbiota of diarrhoea-predominant irritable bowel syndrome sufferers[J].BMC Gastroenterol,2009,9:95.
[41]Salonen A,de Vos WM,Palva A.Gastrointestinal microbiota in irritable bowel syndrome:Present state and perspectives[J].Microbiology,2010,156(Pt 11):3205-3215.
[42]Rajili stojanovi M,Biagi E,Heilig HG,et al.Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome[J].Gastroenterology,2011,141(5):1792-1801.
[43]Jeffery IB,O'Toole PW,Ohman L,et al.An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota[J].Gut,2012,61(7):997-1006.
[44]Penhale WJ,Young PR.The influence of the normal microbial flora on the susceptibility of rats to experimental autoimmune thyroidi tis[J].Clin Exp Immunol,1988,72(2):288-292.
[45]Burek CL,Talor MV.Environmental triggers of autoimmune thyroiditis[J].J Autoimmun,2009,33(3/4):183-189.
[46]Horie I,Abiru N,Nagayama Y,et al.T helper type 17 immune response plays an indispensable role for development of iodineinduced autoimmune thyroiditis in nonobese diabetic-H2h4 mice[J].Endocrinology,2009,150(11):5135-1542.
[47]Yu S,Maiti PK,Dyson M,et al.B cell-deficient NOD.H-2h4mice have CD4+CD25+T regulatory cells that inhibit the development of spontaneous autoimmune thyroiditis[J].J Exp Med,2006,203(2):349-258.
[48]Moshkelgosha S,Masetti G,Berchner-Pfannschmidt U,et al.Gut Microbiome in BALB/c and C57BL/6J Mice Undergoing Experimental Thyroid Autoimmunity Associate with Differences in Immunological Responses and Thyroid Function[J].Horm Metab Res,2018,50(12):932-941.
[49]Masetti G,Moshkelgosha S,Kohling HL,et al.Gut microbiota in experimental murine model of Graves'orbitopathy established in different environments may modulate clinical presentation of disease[J].Microbiome,2018,6(1):97.
[50]Goldberg EA,Venkat-Ramani T,Hewit M,et al.Epidemiology and clinical outcomes of patients with Fusobacterium bacteraemia[J].Epidemiol Infect,2013,141(2):325-329.
[51]Kostic AD,Gevers D,Pedamallu CS,et al.Genomic analysis identifies association of Fusobacterium with colorectal carcinoma[J].Genome Res,2012,22(2):292-298.
[52]Mccoy AN,Araújo-Pérez F,Azcárate-Peril A,et al.Fusobacterium is associated with colorectal adenomas[J].PLo S One,2013,8(1):e53653.
[53]He Z,Shao T,Li H,et al.Alterations of the gut microbiome in Chinese patients with systemic lupus erythematosus[J].Gut Pathog,2016,8(1):64.
[54]Huang F,Qiao HM,Yin JN,et al.Early-life exposure to clostridium leptum causes pulmonary immunosuppression[J].PLo S One,2015,10(11):e0141717.
[55]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.