肠道微生物与自身免疫性肝病研究进展与评价
|
摘要
目前,已被证实与肠道微生物有关的疾病涉及人体的多个器官系统疾病的发生与发展.肠道微生物群是微生物抗原和活化免疫细胞的蓄积体,肠道菌群组成的改变(生物障碍)可以破坏肠道和共生菌的系统免疫耐受性.肠内的Toll样受体可以识别微生物相关的分子模式和T辅助淋巴细胞的形状亚群,这些亚群可以与宿主抗原(分子模拟)交叉反应.活化的肠源性淋巴细胞可以迁移到淋巴结,肠源性微生物抗原可以转移到肠外部位.炎症小体可以在肝细胞和肝星状细胞中形成,它们可以驱动促炎、免疫介导和纤维化反应.本文就肠道微生物在自身免疫性肝病发病机制和治疗上的作用的研究作一综述和评价.
At present, it has been proved that intestinal microbialrelated disorders are involved in the development and progression of multi-organ system diseases. Intestinal microflora is the accumulation of microbial antigens and activated immune cells. Changes in the composition of intestinal microflora(biological disorders) can destroy the systemic immune tolerance of intestinal andsymbiotic bacteria. Toll-like receptors in the intestine recognize microbial-related molecular patterns and T helper lymphocyte subpopulations that can crossreact with host antigens(molecular mimics). Activated enterogenous lymphocytes can migrate to lymph nodes, and enterogenous microbial antigens can migrate to extraintestinal sites. Inflammasomes can form in hepatocytes and hepatic stellate cells, which can drive inflammatory, immune-mediated and fibrotic responses. This article reviews and evaluates the role of intestinal microorganisms in the pathogenesis and treatment of autoimmune liver disease.
At present, it has been proved that intestinal microbialrelated disorders are involved in the development and progression of multi-organ system diseases. Intestinal microflora is the accumulation of microbial antigens and activated immune cells. Changes in the composition of intestinal microflora(biological disorders) can destroy the systemic immune tolerance of intestinal andsymbiotic bacteria. Toll-like receptors in the intestine recognize microbial-related molecular patterns and T helper lymphocyte subpopulations that can crossreact with host antigens(molecular mimics). Activated enterogenous lymphocytes can migrate to lymph nodes, and enterogenous microbial antigens can migrate to extraintestinal sites. Inflammasomes can form in hepatocytes and hepatic stellate cells, which can drive inflammatory, immune-mediated and fibrotic responses. This article reviews and evaluates the role of intestinal microorganisms in the pathogenesis and treatment of autoimmune liver disease.
引文
1 Manns MP,Czaja AJ,Gorham JD,Krawitt EL,Mieli-Vergani G,Vergani D,Vierling JM;American Association for the Study of Liver Diseases.Diagnosis and management of autoimmune hepatitis.Hepatology 2010;51:2193-2213[PMID:20513004 DOI:10.1002/hep.23584]
2 Czaja AJ.Transitioning from Idiopathic to Explainable Autoimmune Hepatitis.Dig Dis Sci 2015;60:2881-2900[PMID:25999246 DOI:10.1007/s10620-015-3708-7]
3 Lin R,Zhou L,Zhang J,Wang B.Abnormal intestinal permeability and microbiota in patients with autoimmune hepatitis.Int J Clin Exp Pathol 2015;8:5153-5160[PMID:26191211]
4 Legutko L.Blood serum iron and copper content depending on the degree of progression of acute leukemia in children.Pediatr Pol 1978;53:817-821[PMID:278954 DOI:10.3748/wjg.v22.i42.9257]
5 Li B,Selmi C,Tang R,Gershwin ME,Ma X.The microbiome and autoimmunity:a paradigm from the gut-liver axis.Cell Mol Immunol 2018;15:595-609[PMID:29706647 DOI:10.1038/cmi.2018.7]
6 Tripathi A,Debelius J,Brenner DA,Karin M,Loomba R,Schnabl B,Knight R.The gut-liver axis and the intersection with the microbiome.Nat Rev Gastroenterol Hepatol 2018;15:397-411[PMID:29748586 DOI:10.1038/s41575-018-0011-z]
7 Wiest R,Garcia-Tsao G.Bacterial translocation(BT)in cirrhosis.Hepatology 2005;41:422-433[PMID:15723320 DOI:10.1002/hep.20632]
8 Seki E,Schnabl B.Role of innate immunity and the microbiota in liver fibrosis:crosstalk between the liver and gut.JPhysiol 2012;590:447-458[PMID:22124143 DOI:10.1113/jphysiol.2011.219691]
9 Son G,Kremer M,Hines IN.Contribution of gut bacteria to liver pathobiology.Gastroenterol Res Pract 2010;2010[PMID:20706692 DOI:10.1155/2010/453563]
10 Takeuchi O,Akira S.Pattern recognition receptors and inflammation.Cell 2010;140:805-820[PMID:20303872 DOI:10.1016/j.cell.2010.01.022]
11 Mejía-León ME,Barca AM.Diet,Microbiota and Immune System in Type 1 Diabetes Development and Evolution.Nutrients 2015;7:9171-9184[PMID:26561831 DOI:10.3390/nu7115461]
12 Wu GD,Chen J,Hoffmann C,Bittinger K,Chen YY,Keilbaugh SA,Bewtra M,Knights D,Walters WA,Knight R,Sinha R,Gilroy E,Gupta K,Baldassano R,Nessel L,Li H,Bushman FD,Lewis JD.Linking long-term dietary patterns with gut microbial enterotypes.Science 2011;334:105-108[PMID:21885731 DOI:10.1126/science.1208344]
13 Vieira SM,Pagovich OE,Kriegel MA.Diet,microbiota and autoimmune diseases.Lupus 2014;23:518-526[PMID:24763536DOI:10.1177/0961203313501401]
14 Konturek PC,Haziri D,Brzozowski T,Hess T,Heyman S,Kwiecien S,Konturek SJ,Koziel J.Emerging role of fecal microbiota therapy in the treatment of gastrointestinal and extra-gastrointestinal diseases.J Physiol Pharmacol 2015;66:483-491[PMID:26348073]
15 López P,González-Rodríguez I,Sánchez B,Ruas-Madiedo P,Suárez A,Margolles A,Gueimonde M.Interaction of Bifidobacterium bifidum LMG13195 with HT29 cells influences regulatory-T-cell-associated chemokine receptor expression.Appl Environ Microbiol 2012;78:2850-2857[PMID:22344636DOI:10.1128/AEM.07581-11]
16 Dolpady J,Sorini C,Di Pietro C,Cosorich I,Ferrarese R,Saita D,Clementi M,Canducci F,Falcone M.Oral Probiotic VSL#3Prevents Autoimmune Diabetes by Modulating Microbiota and Promoting Indoleamine 2,3-Dioxygenase-Enriched Tolerogenic Intestinal Environment.J Diabetes Res 2016;2016:7569431[PMID:26779542 DOI:10.1155/2016/7569431]
17 Zhang H,Liao X,Sparks JB,Luo XM.Dynamics of gut microbiota in autoimmune lupus.Appl Environ Microbiol 2014;80:7551-7560[PMID:25261516 DOI:10.1128/AEM.02676-14]
18 Hsieh CC,Lin BF.Dietary factors regulate cytokines in murine models of systemic lupus erythematosus.Autoimmun Rev 2011;11:22-27[PMID:21763466 DOI:10.1016/j.autrev.2011.06.009]
19 Francino MP.Antibiotics and the Human Gut Microbiome:Dysbioses and Accumulation of Resistances.Front Microbiol2016;6:1543[PMID:26793178 DOI:10.3389/fmicb.2015.01543]
20 Sánchez B,Hevia A,González S,Margolles A.Interaction of Intestinal Microorganisms with the Human Host in the Framework of Autoimmune Diseases.Front Immunol 2015;6:594[PMID:26635808 DOI:10.3389/fimmu.2015.00594]
21 Round JL,Mazmanian SK.Inducible Foxp3+regulatory T-cell development by a commensal bacterium of the intestinal microbiota.Proc Natl Acad Sci USA 2010;107:12204-12209[PMID:20566854 DOI:10.1073/pnas.0909122107]
22 Atarashi K,Tanoue T,Shima T,Imaoka A,Kuwahara T,Momose Y,Cheng G,Yamasaki S,Saito T,Ohba Y,Taniguchi T,Takeda K,Hori S,Ivanov II,Umesaki Y,Itoh K,Honda K.Induction of colonic regulatory T cells by indigenous Clostridium species.Science 2011;331:337-341[PMID:21205640DOI:10.1126/science.1198469]
23 Atarashi K,Tanoue T,Oshima K,Suda W,Nagano Y,Nishikawa H,Fukuda S,Saito T,Narushima S,Hase K,Kim S,Fritz JV,Wilmes P,Ueha S,Matsushima K,Ohno H,Olle B,Sakaguchi S,Taniguchi T,Morita H,Hattori M,Honda K.Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota.Nature 2013;500:232-236[PMID:23842501 DOI:10.1038/nature12331]
24 Lopetuso LR,Scaldaferri F,Bruno G,Petito V,Franceschi F,Gasbarrini A.The therapeutic management of gut barrier leaking:the emerging role for mucosal barrier protectors.Eur Rev Med Pharmacol Sci 2015;19:1068-1076[PMID:25855934]
25 Frasca G,Cardile V,Puglia C,Bonina C,Bonina F.Gelatin tannate reduces the proinflammatory effects of lipopolysaccharide in human intestinal epithelial cells.Clin Exp Gastroenterol 2012;5:61-67[PMID:22629114 DOI:10.2147/CEG.S28792]
26 Wiest R,Albillos A,Trauner M,Bajaj JS,Jalan R.Corrigendum to“Targeting the gut-liver axis in liver disease”[J Hepatol 67(2017)1084-1103].J Hepatol 2018;68:1336[PMID:29655855DOI:10.1016/j.jhep.2018.03.001]
27 Furusawa Y,Obata Y,Fukuda S,Endo TA,Nakato G,Takahashi D,Nakanishi Y,Uetake C,Kato K,Kato T,Takahashi M,Fukuda NN,Murakami S,Miyauchi E,Hino S,Atarashi K,Onawa S,Fujimura Y,Lockett T,Clarke JM,Topping DL,Tomita M,Hori S,Ohara O,Morita T,Koseki H,Kikuchi J,Honda K,Hase K,Ohno H.Commensal microbe-derived butyrate induces the differentiation of colonic regulatory Tcells.Nature 2013;504:446-450[PMID:24226770 DOI:10.1038/nature12721]
28 Manfredo Vieira S,Hiltensperger M,Kumar V,Zegarra-Ruiz D,Dehner C,Khan N,Costa FRC,Tiniakou E,Greiling T,Ruff W,Barbieri A,Kriegel C,Mehta SS,Knight JR,Jain D,Goodman AL,Kriegel MA.Translocation of a gut pathobiont drives autoimmunity in mice and humans.Science 2018;359:1156-1161[PMID:29590047 DOI:10.1126/science.aar7201]
29 Spadoni I,Zagato E,Bertocchi A,Paolinelli R,Hot E,Di Sabatino A,Caprioli F,Bottiglieri L,Oldani A,Viale G,Penna G,Dejana E,Rescigno M.A gut-vascular barrier controls the systemic dissemination of bacteria.Science 2015;350:830-834[PMID:26564856]
30 Henao-Mejia J,Elinav E,Jin C,Hao L,Mehal WZ,Strowig T,Thaiss CA,Kau AL,Eisenbarth SC,Jurczak MJ,Camporez JP,Shulman GI,Gordon JI,Hoffman HM,Flavell RA.Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity.Nature 2012;482:179-185[PMID:22297845DOI:10.1038/nature10809]
31 Haruta I,Kikuchi K,Hashimoto E,Nakamura M,Miyakawa H,Hirota K,Shibata N,Kato H,Arimura Y,Kato Y,Uchiyama T,Nagamune H,Kobayashi M,Miyake Y,Shiratori K,Yagi J.Long-term bacterial exposure can trigger nonsuppurative destructive cholangitis associated with multifocal epithelial inflammation.Lab Invest 2010;90:577-588[PMID:0142809 DOI:10.1038/labinvest.2010.40]
32 Terjung B,S?hne J,Lechtenberg B,Gottwein J,Muennich M,Herzog V,M?hler M,Sauerbruch T,Spengler U.p-ANCAs in autoimmune liver disorders recognise human beta-tubulin isotype 5 and cross-react with microbial protein FtsZ.Gut 2010;59:808-816[PMID:19951907 DOI:10.1136/gut.2008.157818]
33 Melum E,Franke A,Schramm C,Weismüller TJ,Gotthardt DN,Offner FA,Juran BD,Laerdahl JK,Labi V,Bj?rnsson E,Weersma RK,Henckaerts L,Teufel A,Rust C,Ellinghaus E,Balschun T,Boberg KM,Ellinghaus D,Bergquist A,Sauer P,Ryu E,Hov JR,Wedemeyer J,Lindkvist B,Wittig M,Porte RJ,Holm K,Gieger C,Wichmann HE,Stokkers P,Ponsioen CY,Runz H,Stiehl A,Wijmenga C,Sterneck M,Vermeire S,Beuers U,Villunger A,Schrumpf E,Lazaridis KN,Manns MP,Schreiber S,Karlsen TH.Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLAsusceptibility loci.Nat Genet 2011;43:17-19[PMID:21151127DOI:10.1038/ng.728]
34 Rupp C,Friedrich K,Folseraas T,Wannhoff A,Bode KA,Weiss KH,Schirmacher P,Sauer P,Stremmel W,Gotthardt DN.Fut2 genotype is a risk factor for dominant stenosis and biliary candida infections in primary sclerosing cholangitis.Aliment Pharmacol Ther 2014;39:873-882[PMID:24612312 DOI:10.1111/apt.12663]
35 Janse M,Lamberts LE,Franke L,Raychaudhuri S,Ellinghaus E,Muri Boberg K,Melum E,Folseraas T,Schrumpf E,Bergquist A,Bj?rnsson E,Fu J,Jan Westra H,Groen HJ,Fehrmann RS,Smolonska J,van den Berg LH,Ophoff RA,Porte RJ,Weismüller TJ,Wedemeyer J,Schramm C,Sterneck M,Günther R,Braun F,Vermeire S,Henckaerts L,Wijmenga C,Ponsioen CY,Schreiber S,Karlsen TH,Franke A,Weersma RK.Three ulcerative colitis susceptibility loci are associated with primary sclerosing cholangitis and indicate a role for IL2,REL,and CARD9.Hepatology 2011;53:1977-1985[PMID:21425313DOI:10.1002/hep.24307]
36 Li X,Shen J,Ran Z.Crosstalk between the gut and the liver via susceptibility loci:Novel advances in inflammatory bowel disease and autoimmune liver disease.Clin Immunol 2017;175:115-123[PMID:27777084 DOI:10.1016/j.clim.2016.10.006]
37 Wannhoff A,Rupp C,Friedrich K,Brune M,Knierim J,Flechtenmacher C,Sauer P,Stremmel W,Hov JR,Schirmacher P,Weiss KH,Gotthardt DN.Inflammation But Not Biliary Obstruction Is Associated With Carbohydrate Antigen 19-9Levels in Patients With Primary Sclerosing Cholangitis.Clin Gastroenterol Hepatol 2015;13:2372-2379[PMID:26192140 DOI:10.1016/j.cgh.2015.07.014]
38 Eksteen B,Grant AJ,Miles A,Curbishley SM,Lalor PF,Hübscher SG,Briskin M,Salmon M,Adams DH.Hepatic endothelial CCL25 mediates the recruitment of CCR9+guthoming lymphocytes to the liver in primary sclerosing cholangitis.J Exp Med 2004;200:1511-1517[PMID:15557349DOI:10.1084/jem.20041035]
39 Trivedi PJ,Bruns T,Ward S,Mai M,Schmidt C,Hirschfield GM,Weston CJ,Adams DH.Intestinal CCL25 expression is increased in colitis and correlates with inflammatory activity.J Autoimmun 2016;68:98-104[PMID:26873648 DOI:10.1016/j.jaut.2016.01.001]
40 Moro-Sibilot L,Blanc P,Taillardet M,Bardel E,Couillault C,Boschetti G,Traverse-Glehen A,Defrance T,Kaiserlian D,Dubois B.Mouse and Human Liver Contain Immunoglobulin A-Secreting Cells Originating From Peyer’s Patches and Directed Against Intestinal Antigens.Gastroenterology 2016;151:311-323[PMID:27132185 DOI:10.1053/j.gastro.2016.04.014]
41 Trivedi PJ,Adams DH.Mucosal immunity in liver autoimmunity:a comprehensive review.J Autoimmun 2013;46:97-111[PMID:23891169 DOI:10.1016/j.jaut.2013.06.013]
42 Wiest R,Albillos A,Trauner M,Bajaj JS,Jalan R.Targeting the gut-liver axis in liver disease.J Hepatol 2017;67:1084-1103[PMID:28526488 DOI:10.1016/j.jhep.2017.05.007]
43 Li Y,Tang R,Leung PSC,Gershwin ME,Ma X.Bile acids and intestinal microbiota in autoimmune cholestatic liver diseases.Autoimmun Rev 2017;16:885-896[PMID:28698093 DOI:10.1016/j.autrev.2017.07.002]
44 Sayin SI,Wahlstr?m A,Felin J,J?ntti S,Marschall HU,Bamberg K,Angelin B,Hy?tyl?inen T,Ore?i?M,B?ckhed F.Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid,a naturally occurring FXRantagonist.Cell Metab 2013;17:225-235[PMID:23395169 DOI:10.1016/j.cmet.2013.01.003]
45 Li F,Jiang C,Krausz KW,Li Y,Albert I,Hao H,Fabre KM,Mitchell JB,Patterson AD,Gonzalez FJ.Microbiome remodelling leads to inhibition of intestinal farnesoid Xreceptor signalling and decreased obesity.Nat Commun 2013;4:2384[PMID:24064762 DOI:10.1038/ncomms3384]
46 Jiang C,Xie C,Li F,Zhang L,Nichols RG,Krausz KW,Cai J,Qi Y,Fang ZZ,Takahashi S,Tanaka N,Desai D,Amin SG,Albert I,Patterson AD,Gonzalez FJ.Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease.J Clin Invest2015;125:386-402[PMID:25500885 DOI:10.1172/JCI76738]
47 Wahlstr?m A,Sayin SI,Marschall HU,B?ckhed F.Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism.Cell Metab 2016;24:41-50[PMID:27320064DOI:10.1016/j.cmet.2016.05.005]
48 Islam KB,Fukiya S,Hagio M,Fujii N,Ishizuka S,Ooka T,Ogura Y,Hayashi T,Yokota A.Bile acid is a host factor that regulates the composition of the cecal microbiota in rats.Gastroenterology 2011;141:1773-1781[PMID:21839040 DOI:10.1053/j.gastro.2011.07.046]
49úbeda M,Lario M,Mu?oz L,Borrero MJ,Rodríguez-Serrano M,Sánchez-Díaz AM,Del Campo R,LledóL,Pastoró,GarcíaBermejo L,Díaz D,álvarez-Mon M,Albillos A.Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats.J Hepatol 2016;64:1049-1057[PMID:26723896 DOI:10.1016/j.jhep.2015.12.010]
50 Parséus A,Sommer N,Sommer F,Caesar R,Molinaro A,St?hlman M,Greiner TU,Perkins R,B?ckhed F.Microbiotainduced obesity requires farnesoid X receptor.Gut 2017;66:429-437[PMID:26740296 DOI:10.1136/gutjnl-2015-310283]
51 Tang R,Wei Y,Li Y,Chen W,Chen H,Wang Q,Yang F,Miao Q,Xiao X,Zhang H,Lian M,Jiang X,Zhang J,Cao Q,Fan Z,Wu M,Qiu D,Fang JY,Ansari A,Gershwin ME,Ma X.Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy.Gut 2018;67:534-541[PMID:28213609 DOI:10.1136/gutjnl-2016-313332]
52 Lv LX,Fang DQ,Shi D,Chen DY,Yan R,Zhu YX,Chen YF,Shao L,Guo FF,Wu WR,Li A,Shi HY,Jiang XW,Jiang HY,Xiao YH,Zheng SS,Li LJ.Alterations and correlations of the gut microbiome,metabolism and immunity in patients with primary biliary cirrhosis.Environ Microbiol 2016;18:2272-2286[PMID:27243236 DOI:10.1111/1462-2920.13401]
53 Hov JR,Kummen M.Intestinal microbiota in primary sclerosing cholangitis.Curr Opin Gastroenterol 2017;33:85-92[PMID:28030369 DOI:10.1097/MOG.0000000000000334]
54 Torres J,Bao X,Goel A,Colombel JF,Pekow J,Jabri B,Williams KM,Castillo A,Odin JA,Meckel K,Fasihuddin F,Peter I,Itzkowitz S,Hu J.The features of mucosa-associated microbiota in primary sclerosing cholangitis.Aliment Pharmacol Ther 2016;43:790-801[PMID:26857969 DOI:10.1111/apt.13552]
55 Quraishi MN,Sergeant M,Kay G,Iqbal T,Chan J,Constantinidou C,Trivedi P,Ferguson J,Adams DH,Pallen M,Hirschfield GM.The gut-adherent microbiota of PSC-IBDis distinct to that of IBD.Gut 2017;66:386-388[PMID:27196590DOI:10.1136/gutjnl-2016-311915]
56 Rossen NG,Fuentes S,Boonstra K,D’Haens GR,Heilig HG,Zoetendal EG,de Vos WM,Ponsioen CY.The mucosaassociated microbiota of PSC patients is characterized by low diversity and low abundance of uncultured Clostridiales II.JCrohns Colitis 2015;9:342-348[PMID:25547975 DOI:10.1093/ecco-jcc/jju023]
57 Kevans D,Tyler AD,Holm K,J?rgensen KK,Vatn MH,Karlsen TH,Kaplan GG,Eksteen B,Gevers D,Hov JR,Silverberg MS.Characterization of Intestinal Microbiota in Ulcerative Colitis Patients with and without Primary Sclerosing Cholangitis.J Crohns Colitis 2016;10:330-337[PMID:26526357 DOI:10.1093/ecco-jcc/jjv204]
58 Rühlemann MC,Heinsen FA,Zenouzi R,Lieb W,Franke A,Schramm C.Faecal microbiota profiles as diagnostic biomarkers in primary sclerosing cholangitis.Gut 2017;66:753-754[PMID:27216937 DOI:10.1136/gutjnl-2016-312180]
59 Sabino J,Vieira-Silva S,Machiels K,Joossens M,Falony G,Ballet V,Ferrante M,Van Assche G,Van der Merwe S,Vermeire S,Raes J.Primary sclerosing cholangitis is characterised by intestinal dysbiosis independent from IBD.Gut 2016;65:1681-1689[PMID:27207975 DOI:10.1136/gutjnl-2015-311004]
60 Rogier R,Koenders MI,Abdollahi-Roodsaz S.Tolllike receptor mediated modulation of T cell response by commensal intestinal microbiota as a trigger for autoimmune arthritis.J Immunol Res 2015;2015:527696[PMID:25802876DOI:10.1155/2015/527696]
61 Turnbaugh PJ,Ridaura VK,Faith JJ,Rey FE,Knight R,Gordon JI.The effect of diet on the human gut microbiome:a metagenomic analysis in humanized gnotobiotic mice.Sci Transl Med 2009;1:6ra14[PMID:20368178 DOI:10.1126/scitranslmed.3000322]
62 Macpherson AJ,Harris NL.Interactions between commensal intestinal bacteria and the immune system.Nat Rev Immunol2004;4:478-485[PMID:15173836 DOI:10.1038/nri1373]
63 Macpherson AJ,Geuking MB,McCoy KD.Immune responses that adapt the intestinal mucosa to commensal intestinal bacteria.Immunology 2005;115:153-162[PMID:15885120 DOI:10.1111/j.1365-2567.2005.02159.x]
64 Round JL,Lee SM,Li J,Tran G,Jabri B,Chatila TA,Mazmanian SK.The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota.Science 2011;332:974-977[PMID:21512004 DOI:10.1126/science.1206095]
65程昉,徐沪济.转录因子FOXP3的研究进展.中国免疫学杂志2008;24:86-89
66 Ignacio A,Morales CI,Camara NO,Almeida RR.Innate Sensing of the Gut Microbiota:Modulation of Inflammatory and Autoimmune Diseases.Front Immunol 2016;7:54[PMID:26925061 DOI:10.3389/fimmu.2016.00054]
67 Miyake Y,Yamamoto K.Role of gut microbiota in liver diseases.Hepatol Res 2013;43:139-146[PMID:22970713 DOI:10.1111/j.1872-034X.2012.01088.x]
68 Strowig T,Henao-Mejia J,Elinav E,Flavell R.Inflammasomes in health and disease.Nature 2012;481:278-286[PMID:22258606 DOI:10.1038/nature10759]
69 Van Praet JT,Donovan E,Vanassche I,Drennan MB,Windels F,Dendooven A,Allais L,Cuvelier CA,van de Loo F,Norris PS,Kruglov AA,Nedospasov SA,Rabot S,Tito R,Raes J,Gaboriau-Routhiau V,Cerf-Bensussan N,Van de Wiele T,Eberl G,Ware CF,Elewaut D.Commensal microbiota influence systemic autoimmune responses.EMBO J 2015;34:466-474[PMID:25599993 DOI:10.15252/embj.201489966]
70 Singh R,Bullard J,Kalra M,Assefa S,Kaul AK,Vonfeldt K,Strom SC,Conrad RS,Sharp HL,Kaul R.Status of bacterial colonization,Toll-like receptor expression and nuclear factorkappa B activation in normal and diseased human livers.Clin Immunol 2011;138:41-49[PMID:20940109 DOI:10.1016/j.clim.2010.09.006]
71 Wu HJ,Ivanov II,Darce J,Hattori K,Shima T,Umesaki Y,Littman DR,Benoist C,Mathis D.Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper17 cells.Immunity 2010;32:815-827[PMID:20620945 DOI:10.1016/j.immuni.2010.06.001]
72 Mattner J.Impact of Microbes on the Pathogenesis of Primary Biliary Cirrhosis(PBC)and Primary Sclerosing Cholangitis(PSC).Int J Mol Sci 2016;17[PMID:27834858 DOI:10.3390/ijms17111864]
73 Manns MP,Griffin KJ,Sullivan KF,Johnson EF.LKM-1autoantibodies recognize a short linear sequence in P450IID6,a cytochrome P-450 monooxygenase.J Clin Invest 1991;88:1370-1378[PMID:1717511 DOI:10.1172/JCI115443]
74 Aitbaev KA,Murkamilov IT,Fomin VV.Liver diseases:The pathogenetic role of the gut microbiome and the potential of treatment for its modulation.Ter Arkh 2017;89:120-128[PMID:28914862 DOI:10.17116/terarkh2017898120-128]
75 Yu L,Wang L,Chen S.Endogenous toll-like receptor ligands and their biological significance.J Cell Mol Med2010;14:2592-2603[P M I D:20629986 D O I:10.1111/j.1582-4934.2010.01127.x]
76 Kuhn KA,Pedraza I,Demoruelle MK.Mucosal immune responses to microbiota in the development of autoimmune disease.Rheum Dis Clin North Am 2014;40:711-725[PMID:25437287 DOI:10.1016/j.rdc.2014.07.013]
77 Frosali S,Pagliari D,Gambassi G,Landolfi R,Pandolfi F,Cianci R.How the Intricate Interaction among Toll-Like Receptors,Microbiota,and Intestinal Immunity Can Influence Gastrointestinal Pathology.J Immunol Res 2015;2015:489821[PMID:26090491 DOI:10.1155/2015/489821]
78 Bonnert TP,Garka KE,Parnet P,Sonoda G,Testa JR,Sims JE.The cloning and characterization of human MyD88:a member of an IL-1 receptor related family.FEBS Lett 1997;402:81-84[PMID:9013863]
79 Yamamoto M,Takeda K.Current views of toll-like receptor signaling pathways.Gastroenterol Res Pract 2010;2010:240365[PMID:21197425 DOI:10.1155/2010/240365]
80 Tseng PH,Matsuzawa A,Zhang W,Mino T,Vignali DA,Karin M.Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokines.Nat Immunol 2010;11:70-75[PMID:19898473 DOI:10.1038/ni.1819]
81 Pasare C,Medzhitov R.Toll-like receptors and acquired immunity.Semin Immunol 2004;16:23-26[PMID:14751760]
82 Seki E,Tsutsui H,Nakano H,Tsuji N,Hoshino K,Adachi O,Adachi K,Futatsugi S,Kuida K,Takeuchi O,Okamura H,Fujimoto J,Akira S,Nakanishi K.Lipopolysaccharide-induced IL-18 secretion from murine Kupffer cells independently of myeloid differentiation factor 88 that is critically involved in induction of production of IL-12 and IL-1beta.J Immunol 2001;166:2651-2657[PMID:11160328]
83 Wu J,Meng Z,Jiang M,Zhang E,Trippler M,Broering R,Bucchi A,Krux F,Dittmer U,Yang D,Roggendorf M,Gerken G,Lu M,Schlaak JF.Toll-like receptor-induced innate immune responses in non-parenchymal liver cells are cell type-specific.Immunology 2010;129:363-374[PMID:19922426 DOI:10.1111/j.1365-2567.2009.03179.x]
84 Tan TG,Sefik E,Geva-Zatorsky N,Kua L,Naskar D,Teng F,Pasman L,Ortiz-Lopez A,Jupp R,Wu HJ,Kasper DL,Benoist C,Mathis D.Identifying species of symbiont bacteria from the human gut that,alone,can induce intestinal Th17 cells in mice.Proc Natl Acad Sci USA 2016;113:E8141-E8150[PMID:27911839 DOI:10.1073/pnas.1617460113]
85 Dillon S,Agrawal A,Van Dyke T,Landreth G,McCauley L,Koh A,Maliszewski C,Akira S,Pulendran B.A Tolllike receptor 2 ligand stimulates Th2 responses in vivo,via induction of extracellular signal-regulated kinase mitogenactivated protein kinase and c-Fos in dendritic cells.J Immunol2004;172:4733-4743[PMID:15067049]
86 Chow JC,Young DW,Golenbock DT,Christ WJ,Gusovsky F.Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction.J Biol Chem 1999;274:10689-10692[PMID:10196138]
87 Kabelitz D.Expression and function of Toll-like receptors in T lymphocytes.Curr Opin Immunol 2007;19:39-45[PMID:17129718 DOI:10.1016/j.coi.2006.11.007]
88 Seki E,De Minicis S,Gwak GY,Kluwe J,Inokuchi S,Bursill CA,Llovet JM,Brenner DA,Schwabe RF.CCR1 and CCR5promote hepatic fibrosis in mice.J Clin Invest 2009;119:1858-1870[PMID:19603542]
89 Roderburg C,Urban GW,Bettermann K,Vucur M,Zimmermann H,Schmidt S,Janssen J,Koppe C,Knolle P,Castoldi M,Tacke F,Trautwein C,Luedde T.Micro-RNAprofiling reveals a role for miR-29 in human and murine liver fibrosis.Hepatology 2011;53:209-218[PMID:20890893 DOI:10.1002/hep.23922]
90 Figueroa L,Xiong Y,Song C,Piao W,Vogel SN,Medvedev AE.The Asp299Gly polymorphism alters TLR4 signaling by interfering with recruitment of MyD88 and TRIF.JImmunol 2012;188:4506-4515[PMID:22474023 DOI:10.4049/jimmunol.1200202]
91 Mueller T,Beutler C,PicóAH,Shibolet O,Pratt DS,Pascher A,Neuhaus P,Wiedenmann B,Berg T,Podolsky DK.Enhanced innate immune responsiveness and intolerance to intestinal endotoxins in human biliary epithelial cells contributes to chronic cholangitis.Liver Int 2011;31:1574-1588[PMID:22093333 DOI:10.1111/j.1478-3231.2011.02635.x]
92 Gao B,Seki E,Brenner DA,Friedman S,Cohen JI,Nagy L,Szabo G,Zakhari S.Innate immunity in alcoholic liver disease.Am J Physiol Gastrointest Liver Physiol 2011;300:G516-G525[PMID:21252049 DOI:10.1152/ajpgi.00537.2010]
93 Schroder K,Tschopp J.The inflammasomes.Cell 2010;140:821-832[PMID:20303873 DOI:10.1016/j.cell.2010.01.040]
94 Davis BK,Wen H,Ting JP.The inflammasome NLRs in immunity,inflammation,and associated diseases.Annu Rev Immunol 2011;29:707-735[PMID:21219188 DOI:10.1146/annurev-immunol-031210-101405]
95 Boaru SG,Borkham-Kamphorst E,Tihaa L,Haas U,Weiskirchen R.Expression analysis of inflammasomes in experimental models of inflammatory and fibrotic liver disease.J Inflamm(Lond)2012;9:49[PMID:23192004 DOI:10.1186/1476-9255-9-49]
96 Csak T,Ganz M,Pespisa J,Kodys K,Dolganiuc A,Szabo G.Fatty acid and endotoxin activate inflammasomes in mouse hepatocytes that release danger signals to stimulate immune cells.Hepatology 2011;54:133-144[PMID:21488066 DOI:10.1002/hep.24341]
97 Henao-Mejia J,Elinav E,Strowig T,Flavell RA.Inflammasomes:far beyond inflammation.Nat Immunol 2012;13:321-324[PMID:22430784 DOI:10.1038/ni.2257]
98 Martinon F,Mayor A,Tschopp J.The inflammasomes:guardians of the body.Annu Rev Immunol 2009;27:229-265[PMID:19302040]
99 Gurung P,Li B,Subbarao Malireddi RK,Lamkanfi M,Geiger TL,Kanneganti TD.Chronic TLR Stimulation Controls NLRP3Inflammasome Activation through IL-10 Mediated Regulation of NLRP3 Expression and Caspase-8 Activation.Sci Rep 2015;5:14488[PMID:26412089]
100 Chuang SY,Yang CH,Chou CC,Chiang YP,Chuang TH,Hsu LC.TLR-induced PAI-2 expression suppresses IL-1βprocessing via increasing autophagy and NLRP3 degradation.Proc Natl Acad Sci USA 2013;110:16079-16084[PMID:24043792DOI:10.1073/pnas.1306556110]
101 B?ckhed F,Ley RE,Sonnenburg JL,Peterson DA,Gordon JI.Host-bacterial mutualism in the human intestine.Science 2005;307:1915-1920[PMID:15790844 DOI:10.1126/science.1104816]
102 Johansson ME,Phillipson M,Petersson J,Velcich A,Holm L,Hansson GC.The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria.Proc Natl Acad Sci USA 2008;105:15064-15069[PMID:18806221 DOI:10.1073/pnas.0803124105]
103 Reunanen J,Kainulainen V,Huuskonen L,Ottman N,Belzer C,Huhtinen H,de Vos WM,Satokari R.Akkermansia muciniphila Adheres to Enterocytes and Strengthens the Integrity of the Epithelial Cell Layer.Appl Environ Microbiol2015;81:3655-3662[P M I D:25795669 D O I:10.1128/AEM.04050-14]
104赵凡,李春保.肠道菌Akkermansia muciniphila的特性及其与机体健康的关系.微生物学通报2017;6:1458-1463[DOI:10.13344/j.microbiol.china.160740]
105 Mukherjee S,Hooper LV.Antimicrobial defense of the intestine.Immunity 2015;42:28-39[PMID:25607457 DOI:10.1016/j.immuni.2014.12.028]
106 Kinnebrew MA,Ubeda C,Zenewicz LA,Smith N,Flavell RA,Pamer EG.Bacterial flagellin stimulates Toll-like receptor 5-dependent defense against vancomycin-resistant Enterococcus infection.J Infect Dis 2010;201:534-543[PMID:20064069 DOI:10.1086/650203]
107 Vaishnava S,Yamamoto M,Severson KM,Ruhn KA,Yu X,Koren O,Ley R,Wakeland EK,Hooper LV.The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine.Science 2011;334:255-258[PMID:21998396 DOI:10.1126/science.1209791]
108 Barreau F,Hugot JP.Intestinal barrier dysfunction triggered by invasive bacteria.Curr Opin Microbiol 2014;17:91-98[PMID:24440560 DOI:10.1016/j.mib.2013.12.003]
109 Epstein M,Wright JM.Severe multisystem disease caused by trimethoprim-sulfamethoxazole:possible role of an in vitro lymphocyte assay.J Allergy Clin Immunol 1990;86:416-417[PMID:2212414 DOI:10.1113/jphysiol.2011.219691]
110 Tan J,McKenzie C,Potamitis M,Thorburn AN,Mackay CR,Macia L.The role of short-chain fatty acids in health and disease.Adv Immunol 2014;121:91-119[PMID:24388214 DOI:10.1016/B978-0-12-800100-4.00003-9]
111 Lewis K,Lutgendorff F,Phan V,S?derholm JD,Sherman PM,Mc Kay DM.Enhanced translocation of bacteria across metabolically stressed epithelia is reduced by butyrate.Inflamm Bowel Dis 2010;16:1138-1148[PMID:20024905 DOI:10.1002/ibd.21177]
112 Arpaia N,Campbell C,Fan X,Dikiy S,van der Veeken J,deRoos P,Liu H,Cross JR,Pfeffer K,Coffer PJ,Rudensky AY.Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation.Nature 2013;504:451-455[PMID:24226773 DOI:10.1038/nature12726]
113 Singh N,Gurav A,Sivaprakasam S,Brady E,Padia R,Shi H,Thangaraju M,Prasad PD,Manicassamy S,Munn DH,Lee JR,Offermanns S,Ganapathy V.Activation of Gpr109a,receptor for niacin and the commensal metabolite butyrate,suppresses colonic inflammation and carcinogenesis.Immunity 2014;40:128-139[PMID:24412617 DOI:10.1016/j.immuni.2013.12.007]
114 Bordonaro M,Lazarova DL,Augenlicht LH,Sartorelli AC.Cell type-and promoter-dependent modulation of the Wnt signaling pathway by sodium butyrate.Int J Cancer 2002;97:42-51[PMID:11774242]
115 Zhang J,Yi M,Zha L,Chen S,Li Z,Li C,Gong M,Deng H,Chu X,Chen J,Zhang Z,Mao L,Sun S.Sodium Butyrate Induces Endoplasmic Reticulum Stress and Autophagy in Colorectal Cells:Implications for Apoptosis.PLoS One2016;11:e0147218[PMID:26784903 DOI:10.1371/journal.pone.0147218]
116 Madrigal-Matute J,Cuervo AM.Regulation of Liver Metabolism by Autophagy.Gastroenterology 2016;150:328-339[PMID:26453774 DOI:10.1053/j.gastro.2015.09.042]
117 Tang Y,Chen Y,Jiang H,Nie D.Short-chain fatty acids induced autophagy serves as an adaptive strategy for retarding mitochondria-mediated apoptotic cell death.Cell Death Differ 2011;18:602-618[PMID:20930850 DOI:10.1038/cdd.2010.117]
118 Czaja AJ.Targeting apoptosis in autoimmune hepatitis.Dig Dis Sci 2014;59:2890-2904[PMID:25038736 DOI:10.1007/s10620-014-3284-2]
119 Duncan SH,Louis P,Flint HJ.Lactate-utilizing bacteria,isolated from human feces,that produce butyrate as a major fermentation product.Appl Environ Microbiol 2004;70:5810-5817[PMID:15466518 DOI:10.1128/AEM.70.10.5810-5817.2004]
120 Vaarala O,Atkinson MA,Neu J.The“perfect storm”for type 1diabetes:the complex interplay between intestinal microbiota,gut permeability,and mucosal immunity.Diabetes 2008;57:2555-2562[PMID:18820210 DOI:10.2337/db08-0331]
121 Bourriaud C,Robins RJ,Martin L,Kozlowski F,Tenailleau E,Cherbut C,Michel C.Lactate is mainly fermented to butyrate by human intestinal microfloras but inter-individual variation is evident.J Appl Microbiol 2005;99:201-212[PMID:15960680DOI:10.1111/j.1365-2672.2005.02605.x]
122 Hov JR,Karlsen TH.The Microbiome in Primary Sclerosing Cholangitis:Current Evidence and Potential Concepts.Semin Liver Dis 2017;37:314-331[PMID:29272894 DOI:10.1055/s-0037-1608801]
123 Korkach VI,Prudnikov VM.Effect of corticotropin and hydrocortisone on the contractility and heat production of skeletal muscles.Fiziol Zh SSSR Im I M Sechenova 1977;63:1553-1557[PMID:201509 DOI:10.1155/2010/305879]
124 Li X,Wang C,Nie J,Lv D,Wang T,Xu Y.Toll-like receptor4 increases intestinal permeability through up-regulation of membrane PKC activity in alcoholic steatohepatitis.Alcohol 2013;47:459-465[PMID:23871536 DOI:10.1016/j.alcohol.2013.05.004]
125 Fasano A.Leaky gut and autoimmune diseases.Clin Rev Allergy Immunol 2012;42:71-78[PMID:22109896 DOI:10.1007/s12016-011-8291-x]
126 Chan ER,Hester J,Kalady M,Xiao H,Li X,Serre D.A novel method for determining microflora composition using dynamic phylogenetic analysis of 16S ribosomal RNA deep sequencing data.Genomics 2011;98:253-259[PMID:21515358DOI:10.1016/j.ygeno.2011.04.002]
127 Mandal RS,Saha S,Das S.Metagenomic surveys of gut microbiota.Genomics Proteomics Bioinformatics 2015;13:148-158[PMID:26184859 DOI:10.1016/j.gpb.2015.02.005]
128 Ma Y,Shi N,Li M,Chen F,Niu H.Applications of Nextgeneration Sequencing in Systemic Autoimmune Diseases.Genomics Proteomics Bioinformatics 2015;13:242-249[PMID:26432094 DOI:10.1016/j.gpb.2015.09.004]
129 Fraher MH,O’Toole PW,Quigley EM.Techniques used to characterize the gut microbiota:a guide for the clinician.Nat Rev Gastroenterol Hepatol 2012;9:312-322[PMID:22450307DOI:10.1038/nrgastro.2012.44]
130 Tottey W,Denonfoux J,Jaziri F,Parisot N,Missaoui M,Hill D,Borrel G,Peyretaillade E,Alric M,Harris HM,Jeffery IB,Claesson MJ,O’Toole PW,Peyret P,Brugère JF.The human gut chip“HuGChip”,an explorative phylogenetic microarray for determining gut microbiome diversity at family level.PLo SOne 2013;8:e62544[PMID:23690942 DOI:10.1371/journal.pone.0062544]
131 Eisen JA.Environmental shotgun sequencing:its potential and challenges for studying the hidden world of microbes.PLo S Biol 2007;5:e82[PMID:17355177 DOI:10.1371/journal.pbio.0050082]
132 Scaldaferri F,Lopetuso LR,Petito V,Cufino V,Bilotta M,Arena V,Stigliano E,Maulucci G,Papi M,Emiliana CM,Poscia A,Franceschi F,Delogu G,Sanguinetti M,Spirito MD,Sgambato A,Gasbarrini A.Gelatin tannate ameliorates acute colitis in mice by reinforcing mucus layer and modulating gut microbiota composition:Emerging role for‘gut barrier protectors’in IBD?United European Gastroenterol J 2014;2:113-122[PMID:24918016 DOI:10.1177/2050640614520867]
133 Bomhof MR,Parnell JA,Ramay HR,Crotty P,Rioux KP,Probert CS,Jayakumar S,Raman M,Reimer RA.Histological improvement of non-alcoholic steatohepatitis with a prebiotic:a pilot clinical trial.Eur J Nutr 2018[PMID:29779170 DOI:10.1007/s00394-018-1721-2]
134 Zhang W,Gu Y,Chen Y,Deng H,Chen L,Chen S,Zhang G,Gao Z.Intestinal flora imbalance results in altered bacterial translocation and liver function in rats with experimental cirrhosis.Eur J Gastroenterol Hepatol 2010;22:1481-1486[PMID:20739895 DOI:10.1097/MEG.0b013e32833eb8b0]
135 Nardone G,Compare D,Liguori E,Di Mauro V,Rocco A,Barone M,Napoli A,Lapi D,Iovene MR,Colantuoni A.Protective effects of Lactobacillus paracasei F19 in a rat model of oxidative and metabolic hepatic injury.Am JPhysiol Gastrointest Liver Physiol 2010;299:G669-G676[PMID:20576921 DOI:10.1152/ajpgi.00188.2010]
136 Tabibian JH,Weeding E,Jorgensen RA,Petz JL,Keach JC,Talwalkar JA,Lindor KD.Randomised clinical trial:vancomycin or metronidazole in patients with primary sclerosing cholangitis-a pilot study.Aliment Pharmacol Ther2013;37:604-612[PMID:23384404 DOI:10.1111/apt.12232]
137 Hommes DW,Erkelens W,Ponsioen C,Stokkers P,Rauws E,van der Spek M,ten Kate F,van Deventer SJ.A double-blind,placebo-controlled,randomized study of infliximab in primary sclerosing cholangitis.J Clin Gastroenterol 2008;42:522-526[PMID:18344886 DOI:10.1097/MCG.0b013e3181662426]
138 Cullen S N,Chapman R W.Reviewarticle:current management of primary sclerosing cholangitis.Aliment Pharmacol Ther 2005;21:933-948[PMID:15813829 DOI:10.1111/j.1365-2036.2005.02407.x]
139 Chapman R,Fevery J,Kalloo A,Nagorney DM,Boberg KM,Shneider B,Gores GJ;American Association for the Study of Liver Diseases.Diagnosis and management of primary sclerosing cholangitis.Hepatology 2010;51:660-678[PMID:20101749 DOI:10.1002/hep.23294]
140 Bj?ro K,Brandsaeter B,Foss A,Schrumpf E.Liver transplantation in primary sclerosing cholangitis.Semin Liver Dis 2006;26:69-79[PMID:16496235 DOI:10.1055/s-2006-933565]
141 Eaton JE,Talwalkar JA,Lazaridis KN,Gores GJ,Lindor KD.Pathogenesis of primary sclerosing cholangitis and advances in diagnosis and management.Gastroenterology 2013;145:521-536[PMID:23827861 DOI:10.1053/j.gastro.2013.06.052]
2 Czaja AJ.Transitioning from Idiopathic to Explainable Autoimmune Hepatitis.Dig Dis Sci 2015;60:2881-2900[PMID:25999246 DOI:10.1007/s10620-015-3708-7]
3 Lin R,Zhou L,Zhang J,Wang B.Abnormal intestinal permeability and microbiota in patients with autoimmune hepatitis.Int J Clin Exp Pathol 2015;8:5153-5160[PMID:26191211]
4 Legutko L.Blood serum iron and copper content depending on the degree of progression of acute leukemia in children.Pediatr Pol 1978;53:817-821[PMID:278954 DOI:10.3748/wjg.v22.i42.9257]
5 Li B,Selmi C,Tang R,Gershwin ME,Ma X.The microbiome and autoimmunity:a paradigm from the gut-liver axis.Cell Mol Immunol 2018;15:595-609[PMID:29706647 DOI:10.1038/cmi.2018.7]
6 Tripathi A,Debelius J,Brenner DA,Karin M,Loomba R,Schnabl B,Knight R.The gut-liver axis and the intersection with the microbiome.Nat Rev Gastroenterol Hepatol 2018;15:397-411[PMID:29748586 DOI:10.1038/s41575-018-0011-z]
7 Wiest R,Garcia-Tsao G.Bacterial translocation(BT)in cirrhosis.Hepatology 2005;41:422-433[PMID:15723320 DOI:10.1002/hep.20632]
8 Seki E,Schnabl B.Role of innate immunity and the microbiota in liver fibrosis:crosstalk between the liver and gut.JPhysiol 2012;590:447-458[PMID:22124143 DOI:10.1113/jphysiol.2011.219691]
9 Son G,Kremer M,Hines IN.Contribution of gut bacteria to liver pathobiology.Gastroenterol Res Pract 2010;2010[PMID:20706692 DOI:10.1155/2010/453563]
10 Takeuchi O,Akira S.Pattern recognition receptors and inflammation.Cell 2010;140:805-820[PMID:20303872 DOI:10.1016/j.cell.2010.01.022]
11 Mejía-León ME,Barca AM.Diet,Microbiota and Immune System in Type 1 Diabetes Development and Evolution.Nutrients 2015;7:9171-9184[PMID:26561831 DOI:10.3390/nu7115461]
12 Wu GD,Chen J,Hoffmann C,Bittinger K,Chen YY,Keilbaugh SA,Bewtra M,Knights D,Walters WA,Knight R,Sinha R,Gilroy E,Gupta K,Baldassano R,Nessel L,Li H,Bushman FD,Lewis JD.Linking long-term dietary patterns with gut microbial enterotypes.Science 2011;334:105-108[PMID:21885731 DOI:10.1126/science.1208344]
13 Vieira SM,Pagovich OE,Kriegel MA.Diet,microbiota and autoimmune diseases.Lupus 2014;23:518-526[PMID:24763536DOI:10.1177/0961203313501401]
14 Konturek PC,Haziri D,Brzozowski T,Hess T,Heyman S,Kwiecien S,Konturek SJ,Koziel J.Emerging role of fecal microbiota therapy in the treatment of gastrointestinal and extra-gastrointestinal diseases.J Physiol Pharmacol 2015;66:483-491[PMID:26348073]
15 López P,González-Rodríguez I,Sánchez B,Ruas-Madiedo P,Suárez A,Margolles A,Gueimonde M.Interaction of Bifidobacterium bifidum LMG13195 with HT29 cells influences regulatory-T-cell-associated chemokine receptor expression.Appl Environ Microbiol 2012;78:2850-2857[PMID:22344636DOI:10.1128/AEM.07581-11]
16 Dolpady J,Sorini C,Di Pietro C,Cosorich I,Ferrarese R,Saita D,Clementi M,Canducci F,Falcone M.Oral Probiotic VSL#3Prevents Autoimmune Diabetes by Modulating Microbiota and Promoting Indoleamine 2,3-Dioxygenase-Enriched Tolerogenic Intestinal Environment.J Diabetes Res 2016;2016:7569431[PMID:26779542 DOI:10.1155/2016/7569431]
17 Zhang H,Liao X,Sparks JB,Luo XM.Dynamics of gut microbiota in autoimmune lupus.Appl Environ Microbiol 2014;80:7551-7560[PMID:25261516 DOI:10.1128/AEM.02676-14]
18 Hsieh CC,Lin BF.Dietary factors regulate cytokines in murine models of systemic lupus erythematosus.Autoimmun Rev 2011;11:22-27[PMID:21763466 DOI:10.1016/j.autrev.2011.06.009]
19 Francino MP.Antibiotics and the Human Gut Microbiome:Dysbioses and Accumulation of Resistances.Front Microbiol2016;6:1543[PMID:26793178 DOI:10.3389/fmicb.2015.01543]
20 Sánchez B,Hevia A,González S,Margolles A.Interaction of Intestinal Microorganisms with the Human Host in the Framework of Autoimmune Diseases.Front Immunol 2015;6:594[PMID:26635808 DOI:10.3389/fimmu.2015.00594]
21 Round JL,Mazmanian SK.Inducible Foxp3+regulatory T-cell development by a commensal bacterium of the intestinal microbiota.Proc Natl Acad Sci USA 2010;107:12204-12209[PMID:20566854 DOI:10.1073/pnas.0909122107]
22 Atarashi K,Tanoue T,Shima T,Imaoka A,Kuwahara T,Momose Y,Cheng G,Yamasaki S,Saito T,Ohba Y,Taniguchi T,Takeda K,Hori S,Ivanov II,Umesaki Y,Itoh K,Honda K.Induction of colonic regulatory T cells by indigenous Clostridium species.Science 2011;331:337-341[PMID:21205640DOI:10.1126/science.1198469]
23 Atarashi K,Tanoue T,Oshima K,Suda W,Nagano Y,Nishikawa H,Fukuda S,Saito T,Narushima S,Hase K,Kim S,Fritz JV,Wilmes P,Ueha S,Matsushima K,Ohno H,Olle B,Sakaguchi S,Taniguchi T,Morita H,Hattori M,Honda K.Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota.Nature 2013;500:232-236[PMID:23842501 DOI:10.1038/nature12331]
24 Lopetuso LR,Scaldaferri F,Bruno G,Petito V,Franceschi F,Gasbarrini A.The therapeutic management of gut barrier leaking:the emerging role for mucosal barrier protectors.Eur Rev Med Pharmacol Sci 2015;19:1068-1076[PMID:25855934]
25 Frasca G,Cardile V,Puglia C,Bonina C,Bonina F.Gelatin tannate reduces the proinflammatory effects of lipopolysaccharide in human intestinal epithelial cells.Clin Exp Gastroenterol 2012;5:61-67[PMID:22629114 DOI:10.2147/CEG.S28792]
26 Wiest R,Albillos A,Trauner M,Bajaj JS,Jalan R.Corrigendum to“Targeting the gut-liver axis in liver disease”[J Hepatol 67(2017)1084-1103].J Hepatol 2018;68:1336[PMID:29655855DOI:10.1016/j.jhep.2018.03.001]
27 Furusawa Y,Obata Y,Fukuda S,Endo TA,Nakato G,Takahashi D,Nakanishi Y,Uetake C,Kato K,Kato T,Takahashi M,Fukuda NN,Murakami S,Miyauchi E,Hino S,Atarashi K,Onawa S,Fujimura Y,Lockett T,Clarke JM,Topping DL,Tomita M,Hori S,Ohara O,Morita T,Koseki H,Kikuchi J,Honda K,Hase K,Ohno H.Commensal microbe-derived butyrate induces the differentiation of colonic regulatory Tcells.Nature 2013;504:446-450[PMID:24226770 DOI:10.1038/nature12721]
28 Manfredo Vieira S,Hiltensperger M,Kumar V,Zegarra-Ruiz D,Dehner C,Khan N,Costa FRC,Tiniakou E,Greiling T,Ruff W,Barbieri A,Kriegel C,Mehta SS,Knight JR,Jain D,Goodman AL,Kriegel MA.Translocation of a gut pathobiont drives autoimmunity in mice and humans.Science 2018;359:1156-1161[PMID:29590047 DOI:10.1126/science.aar7201]
29 Spadoni I,Zagato E,Bertocchi A,Paolinelli R,Hot E,Di Sabatino A,Caprioli F,Bottiglieri L,Oldani A,Viale G,Penna G,Dejana E,Rescigno M.A gut-vascular barrier controls the systemic dissemination of bacteria.Science 2015;350:830-834[PMID:26564856]
30 Henao-Mejia J,Elinav E,Jin C,Hao L,Mehal WZ,Strowig T,Thaiss CA,Kau AL,Eisenbarth SC,Jurczak MJ,Camporez JP,Shulman GI,Gordon JI,Hoffman HM,Flavell RA.Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity.Nature 2012;482:179-185[PMID:22297845DOI:10.1038/nature10809]
31 Haruta I,Kikuchi K,Hashimoto E,Nakamura M,Miyakawa H,Hirota K,Shibata N,Kato H,Arimura Y,Kato Y,Uchiyama T,Nagamune H,Kobayashi M,Miyake Y,Shiratori K,Yagi J.Long-term bacterial exposure can trigger nonsuppurative destructive cholangitis associated with multifocal epithelial inflammation.Lab Invest 2010;90:577-588[PMID:0142809 DOI:10.1038/labinvest.2010.40]
32 Terjung B,S?hne J,Lechtenberg B,Gottwein J,Muennich M,Herzog V,M?hler M,Sauerbruch T,Spengler U.p-ANCAs in autoimmune liver disorders recognise human beta-tubulin isotype 5 and cross-react with microbial protein FtsZ.Gut 2010;59:808-816[PMID:19951907 DOI:10.1136/gut.2008.157818]
33 Melum E,Franke A,Schramm C,Weismüller TJ,Gotthardt DN,Offner FA,Juran BD,Laerdahl JK,Labi V,Bj?rnsson E,Weersma RK,Henckaerts L,Teufel A,Rust C,Ellinghaus E,Balschun T,Boberg KM,Ellinghaus D,Bergquist A,Sauer P,Ryu E,Hov JR,Wedemeyer J,Lindkvist B,Wittig M,Porte RJ,Holm K,Gieger C,Wichmann HE,Stokkers P,Ponsioen CY,Runz H,Stiehl A,Wijmenga C,Sterneck M,Vermeire S,Beuers U,Villunger A,Schrumpf E,Lazaridis KN,Manns MP,Schreiber S,Karlsen TH.Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLAsusceptibility loci.Nat Genet 2011;43:17-19[PMID:21151127DOI:10.1038/ng.728]
34 Rupp C,Friedrich K,Folseraas T,Wannhoff A,Bode KA,Weiss KH,Schirmacher P,Sauer P,Stremmel W,Gotthardt DN.Fut2 genotype is a risk factor for dominant stenosis and biliary candida infections in primary sclerosing cholangitis.Aliment Pharmacol Ther 2014;39:873-882[PMID:24612312 DOI:10.1111/apt.12663]
35 Janse M,Lamberts LE,Franke L,Raychaudhuri S,Ellinghaus E,Muri Boberg K,Melum E,Folseraas T,Schrumpf E,Bergquist A,Bj?rnsson E,Fu J,Jan Westra H,Groen HJ,Fehrmann RS,Smolonska J,van den Berg LH,Ophoff RA,Porte RJ,Weismüller TJ,Wedemeyer J,Schramm C,Sterneck M,Günther R,Braun F,Vermeire S,Henckaerts L,Wijmenga C,Ponsioen CY,Schreiber S,Karlsen TH,Franke A,Weersma RK.Three ulcerative colitis susceptibility loci are associated with primary sclerosing cholangitis and indicate a role for IL2,REL,and CARD9.Hepatology 2011;53:1977-1985[PMID:21425313DOI:10.1002/hep.24307]
36 Li X,Shen J,Ran Z.Crosstalk between the gut and the liver via susceptibility loci:Novel advances in inflammatory bowel disease and autoimmune liver disease.Clin Immunol 2017;175:115-123[PMID:27777084 DOI:10.1016/j.clim.2016.10.006]
37 Wannhoff A,Rupp C,Friedrich K,Brune M,Knierim J,Flechtenmacher C,Sauer P,Stremmel W,Hov JR,Schirmacher P,Weiss KH,Gotthardt DN.Inflammation But Not Biliary Obstruction Is Associated With Carbohydrate Antigen 19-9Levels in Patients With Primary Sclerosing Cholangitis.Clin Gastroenterol Hepatol 2015;13:2372-2379[PMID:26192140 DOI:10.1016/j.cgh.2015.07.014]
38 Eksteen B,Grant AJ,Miles A,Curbishley SM,Lalor PF,Hübscher SG,Briskin M,Salmon M,Adams DH.Hepatic endothelial CCL25 mediates the recruitment of CCR9+guthoming lymphocytes to the liver in primary sclerosing cholangitis.J Exp Med 2004;200:1511-1517[PMID:15557349DOI:10.1084/jem.20041035]
39 Trivedi PJ,Bruns T,Ward S,Mai M,Schmidt C,Hirschfield GM,Weston CJ,Adams DH.Intestinal CCL25 expression is increased in colitis and correlates with inflammatory activity.J Autoimmun 2016;68:98-104[PMID:26873648 DOI:10.1016/j.jaut.2016.01.001]
40 Moro-Sibilot L,Blanc P,Taillardet M,Bardel E,Couillault C,Boschetti G,Traverse-Glehen A,Defrance T,Kaiserlian D,Dubois B.Mouse and Human Liver Contain Immunoglobulin A-Secreting Cells Originating From Peyer’s Patches and Directed Against Intestinal Antigens.Gastroenterology 2016;151:311-323[PMID:27132185 DOI:10.1053/j.gastro.2016.04.014]
41 Trivedi PJ,Adams DH.Mucosal immunity in liver autoimmunity:a comprehensive review.J Autoimmun 2013;46:97-111[PMID:23891169 DOI:10.1016/j.jaut.2013.06.013]
42 Wiest R,Albillos A,Trauner M,Bajaj JS,Jalan R.Targeting the gut-liver axis in liver disease.J Hepatol 2017;67:1084-1103[PMID:28526488 DOI:10.1016/j.jhep.2017.05.007]
43 Li Y,Tang R,Leung PSC,Gershwin ME,Ma X.Bile acids and intestinal microbiota in autoimmune cholestatic liver diseases.Autoimmun Rev 2017;16:885-896[PMID:28698093 DOI:10.1016/j.autrev.2017.07.002]
44 Sayin SI,Wahlstr?m A,Felin J,J?ntti S,Marschall HU,Bamberg K,Angelin B,Hy?tyl?inen T,Ore?i?M,B?ckhed F.Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid,a naturally occurring FXRantagonist.Cell Metab 2013;17:225-235[PMID:23395169 DOI:10.1016/j.cmet.2013.01.003]
45 Li F,Jiang C,Krausz KW,Li Y,Albert I,Hao H,Fabre KM,Mitchell JB,Patterson AD,Gonzalez FJ.Microbiome remodelling leads to inhibition of intestinal farnesoid Xreceptor signalling and decreased obesity.Nat Commun 2013;4:2384[PMID:24064762 DOI:10.1038/ncomms3384]
46 Jiang C,Xie C,Li F,Zhang L,Nichols RG,Krausz KW,Cai J,Qi Y,Fang ZZ,Takahashi S,Tanaka N,Desai D,Amin SG,Albert I,Patterson AD,Gonzalez FJ.Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease.J Clin Invest2015;125:386-402[PMID:25500885 DOI:10.1172/JCI76738]
47 Wahlstr?m A,Sayin SI,Marschall HU,B?ckhed F.Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism.Cell Metab 2016;24:41-50[PMID:27320064DOI:10.1016/j.cmet.2016.05.005]
48 Islam KB,Fukiya S,Hagio M,Fujii N,Ishizuka S,Ooka T,Ogura Y,Hayashi T,Yokota A.Bile acid is a host factor that regulates the composition of the cecal microbiota in rats.Gastroenterology 2011;141:1773-1781[PMID:21839040 DOI:10.1053/j.gastro.2011.07.046]
49úbeda M,Lario M,Mu?oz L,Borrero MJ,Rodríguez-Serrano M,Sánchez-Díaz AM,Del Campo R,LledóL,Pastoró,GarcíaBermejo L,Díaz D,álvarez-Mon M,Albillos A.Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats.J Hepatol 2016;64:1049-1057[PMID:26723896 DOI:10.1016/j.jhep.2015.12.010]
50 Parséus A,Sommer N,Sommer F,Caesar R,Molinaro A,St?hlman M,Greiner TU,Perkins R,B?ckhed F.Microbiotainduced obesity requires farnesoid X receptor.Gut 2017;66:429-437[PMID:26740296 DOI:10.1136/gutjnl-2015-310283]
51 Tang R,Wei Y,Li Y,Chen W,Chen H,Wang Q,Yang F,Miao Q,Xiao X,Zhang H,Lian M,Jiang X,Zhang J,Cao Q,Fan Z,Wu M,Qiu D,Fang JY,Ansari A,Gershwin ME,Ma X.Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy.Gut 2018;67:534-541[PMID:28213609 DOI:10.1136/gutjnl-2016-313332]
52 Lv LX,Fang DQ,Shi D,Chen DY,Yan R,Zhu YX,Chen YF,Shao L,Guo FF,Wu WR,Li A,Shi HY,Jiang XW,Jiang HY,Xiao YH,Zheng SS,Li LJ.Alterations and correlations of the gut microbiome,metabolism and immunity in patients with primary biliary cirrhosis.Environ Microbiol 2016;18:2272-2286[PMID:27243236 DOI:10.1111/1462-2920.13401]
53 Hov JR,Kummen M.Intestinal microbiota in primary sclerosing cholangitis.Curr Opin Gastroenterol 2017;33:85-92[PMID:28030369 DOI:10.1097/MOG.0000000000000334]
54 Torres J,Bao X,Goel A,Colombel JF,Pekow J,Jabri B,Williams KM,Castillo A,Odin JA,Meckel K,Fasihuddin F,Peter I,Itzkowitz S,Hu J.The features of mucosa-associated microbiota in primary sclerosing cholangitis.Aliment Pharmacol Ther 2016;43:790-801[PMID:26857969 DOI:10.1111/apt.13552]
55 Quraishi MN,Sergeant M,Kay G,Iqbal T,Chan J,Constantinidou C,Trivedi P,Ferguson J,Adams DH,Pallen M,Hirschfield GM.The gut-adherent microbiota of PSC-IBDis distinct to that of IBD.Gut 2017;66:386-388[PMID:27196590DOI:10.1136/gutjnl-2016-311915]
56 Rossen NG,Fuentes S,Boonstra K,D’Haens GR,Heilig HG,Zoetendal EG,de Vos WM,Ponsioen CY.The mucosaassociated microbiota of PSC patients is characterized by low diversity and low abundance of uncultured Clostridiales II.JCrohns Colitis 2015;9:342-348[PMID:25547975 DOI:10.1093/ecco-jcc/jju023]
57 Kevans D,Tyler AD,Holm K,J?rgensen KK,Vatn MH,Karlsen TH,Kaplan GG,Eksteen B,Gevers D,Hov JR,Silverberg MS.Characterization of Intestinal Microbiota in Ulcerative Colitis Patients with and without Primary Sclerosing Cholangitis.J Crohns Colitis 2016;10:330-337[PMID:26526357 DOI:10.1093/ecco-jcc/jjv204]
58 Rühlemann MC,Heinsen FA,Zenouzi R,Lieb W,Franke A,Schramm C.Faecal microbiota profiles as diagnostic biomarkers in primary sclerosing cholangitis.Gut 2017;66:753-754[PMID:27216937 DOI:10.1136/gutjnl-2016-312180]
59 Sabino J,Vieira-Silva S,Machiels K,Joossens M,Falony G,Ballet V,Ferrante M,Van Assche G,Van der Merwe S,Vermeire S,Raes J.Primary sclerosing cholangitis is characterised by intestinal dysbiosis independent from IBD.Gut 2016;65:1681-1689[PMID:27207975 DOI:10.1136/gutjnl-2015-311004]
60 Rogier R,Koenders MI,Abdollahi-Roodsaz S.Tolllike receptor mediated modulation of T cell response by commensal intestinal microbiota as a trigger for autoimmune arthritis.J Immunol Res 2015;2015:527696[PMID:25802876DOI:10.1155/2015/527696]
61 Turnbaugh PJ,Ridaura VK,Faith JJ,Rey FE,Knight R,Gordon JI.The effect of diet on the human gut microbiome:a metagenomic analysis in humanized gnotobiotic mice.Sci Transl Med 2009;1:6ra14[PMID:20368178 DOI:10.1126/scitranslmed.3000322]
62 Macpherson AJ,Harris NL.Interactions between commensal intestinal bacteria and the immune system.Nat Rev Immunol2004;4:478-485[PMID:15173836 DOI:10.1038/nri1373]
63 Macpherson AJ,Geuking MB,McCoy KD.Immune responses that adapt the intestinal mucosa to commensal intestinal bacteria.Immunology 2005;115:153-162[PMID:15885120 DOI:10.1111/j.1365-2567.2005.02159.x]
64 Round JL,Lee SM,Li J,Tran G,Jabri B,Chatila TA,Mazmanian SK.The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota.Science 2011;332:974-977[PMID:21512004 DOI:10.1126/science.1206095]
65程昉,徐沪济.转录因子FOXP3的研究进展.中国免疫学杂志2008;24:86-89
66 Ignacio A,Morales CI,Camara NO,Almeida RR.Innate Sensing of the Gut Microbiota:Modulation of Inflammatory and Autoimmune Diseases.Front Immunol 2016;7:54[PMID:26925061 DOI:10.3389/fimmu.2016.00054]
67 Miyake Y,Yamamoto K.Role of gut microbiota in liver diseases.Hepatol Res 2013;43:139-146[PMID:22970713 DOI:10.1111/j.1872-034X.2012.01088.x]
68 Strowig T,Henao-Mejia J,Elinav E,Flavell R.Inflammasomes in health and disease.Nature 2012;481:278-286[PMID:22258606 DOI:10.1038/nature10759]
69 Van Praet JT,Donovan E,Vanassche I,Drennan MB,Windels F,Dendooven A,Allais L,Cuvelier CA,van de Loo F,Norris PS,Kruglov AA,Nedospasov SA,Rabot S,Tito R,Raes J,Gaboriau-Routhiau V,Cerf-Bensussan N,Van de Wiele T,Eberl G,Ware CF,Elewaut D.Commensal microbiota influence systemic autoimmune responses.EMBO J 2015;34:466-474[PMID:25599993 DOI:10.15252/embj.201489966]
70 Singh R,Bullard J,Kalra M,Assefa S,Kaul AK,Vonfeldt K,Strom SC,Conrad RS,Sharp HL,Kaul R.Status of bacterial colonization,Toll-like receptor expression and nuclear factorkappa B activation in normal and diseased human livers.Clin Immunol 2011;138:41-49[PMID:20940109 DOI:10.1016/j.clim.2010.09.006]
71 Wu HJ,Ivanov II,Darce J,Hattori K,Shima T,Umesaki Y,Littman DR,Benoist C,Mathis D.Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper17 cells.Immunity 2010;32:815-827[PMID:20620945 DOI:10.1016/j.immuni.2010.06.001]
72 Mattner J.Impact of Microbes on the Pathogenesis of Primary Biliary Cirrhosis(PBC)and Primary Sclerosing Cholangitis(PSC).Int J Mol Sci 2016;17[PMID:27834858 DOI:10.3390/ijms17111864]
73 Manns MP,Griffin KJ,Sullivan KF,Johnson EF.LKM-1autoantibodies recognize a short linear sequence in P450IID6,a cytochrome P-450 monooxygenase.J Clin Invest 1991;88:1370-1378[PMID:1717511 DOI:10.1172/JCI115443]
74 Aitbaev KA,Murkamilov IT,Fomin VV.Liver diseases:The pathogenetic role of the gut microbiome and the potential of treatment for its modulation.Ter Arkh 2017;89:120-128[PMID:28914862 DOI:10.17116/terarkh2017898120-128]
75 Yu L,Wang L,Chen S.Endogenous toll-like receptor ligands and their biological significance.J Cell Mol Med2010;14:2592-2603[P M I D:20629986 D O I:10.1111/j.1582-4934.2010.01127.x]
76 Kuhn KA,Pedraza I,Demoruelle MK.Mucosal immune responses to microbiota in the development of autoimmune disease.Rheum Dis Clin North Am 2014;40:711-725[PMID:25437287 DOI:10.1016/j.rdc.2014.07.013]
77 Frosali S,Pagliari D,Gambassi G,Landolfi R,Pandolfi F,Cianci R.How the Intricate Interaction among Toll-Like Receptors,Microbiota,and Intestinal Immunity Can Influence Gastrointestinal Pathology.J Immunol Res 2015;2015:489821[PMID:26090491 DOI:10.1155/2015/489821]
78 Bonnert TP,Garka KE,Parnet P,Sonoda G,Testa JR,Sims JE.The cloning and characterization of human MyD88:a member of an IL-1 receptor related family.FEBS Lett 1997;402:81-84[PMID:9013863]
79 Yamamoto M,Takeda K.Current views of toll-like receptor signaling pathways.Gastroenterol Res Pract 2010;2010:240365[PMID:21197425 DOI:10.1155/2010/240365]
80 Tseng PH,Matsuzawa A,Zhang W,Mino T,Vignali DA,Karin M.Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokines.Nat Immunol 2010;11:70-75[PMID:19898473 DOI:10.1038/ni.1819]
81 Pasare C,Medzhitov R.Toll-like receptors and acquired immunity.Semin Immunol 2004;16:23-26[PMID:14751760]
82 Seki E,Tsutsui H,Nakano H,Tsuji N,Hoshino K,Adachi O,Adachi K,Futatsugi S,Kuida K,Takeuchi O,Okamura H,Fujimoto J,Akira S,Nakanishi K.Lipopolysaccharide-induced IL-18 secretion from murine Kupffer cells independently of myeloid differentiation factor 88 that is critically involved in induction of production of IL-12 and IL-1beta.J Immunol 2001;166:2651-2657[PMID:11160328]
83 Wu J,Meng Z,Jiang M,Zhang E,Trippler M,Broering R,Bucchi A,Krux F,Dittmer U,Yang D,Roggendorf M,Gerken G,Lu M,Schlaak JF.Toll-like receptor-induced innate immune responses in non-parenchymal liver cells are cell type-specific.Immunology 2010;129:363-374[PMID:19922426 DOI:10.1111/j.1365-2567.2009.03179.x]
84 Tan TG,Sefik E,Geva-Zatorsky N,Kua L,Naskar D,Teng F,Pasman L,Ortiz-Lopez A,Jupp R,Wu HJ,Kasper DL,Benoist C,Mathis D.Identifying species of symbiont bacteria from the human gut that,alone,can induce intestinal Th17 cells in mice.Proc Natl Acad Sci USA 2016;113:E8141-E8150[PMID:27911839 DOI:10.1073/pnas.1617460113]
85 Dillon S,Agrawal A,Van Dyke T,Landreth G,McCauley L,Koh A,Maliszewski C,Akira S,Pulendran B.A Tolllike receptor 2 ligand stimulates Th2 responses in vivo,via induction of extracellular signal-regulated kinase mitogenactivated protein kinase and c-Fos in dendritic cells.J Immunol2004;172:4733-4743[PMID:15067049]
86 Chow JC,Young DW,Golenbock DT,Christ WJ,Gusovsky F.Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction.J Biol Chem 1999;274:10689-10692[PMID:10196138]
87 Kabelitz D.Expression and function of Toll-like receptors in T lymphocytes.Curr Opin Immunol 2007;19:39-45[PMID:17129718 DOI:10.1016/j.coi.2006.11.007]
88 Seki E,De Minicis S,Gwak GY,Kluwe J,Inokuchi S,Bursill CA,Llovet JM,Brenner DA,Schwabe RF.CCR1 and CCR5promote hepatic fibrosis in mice.J Clin Invest 2009;119:1858-1870[PMID:19603542]
89 Roderburg C,Urban GW,Bettermann K,Vucur M,Zimmermann H,Schmidt S,Janssen J,Koppe C,Knolle P,Castoldi M,Tacke F,Trautwein C,Luedde T.Micro-RNAprofiling reveals a role for miR-29 in human and murine liver fibrosis.Hepatology 2011;53:209-218[PMID:20890893 DOI:10.1002/hep.23922]
90 Figueroa L,Xiong Y,Song C,Piao W,Vogel SN,Medvedev AE.The Asp299Gly polymorphism alters TLR4 signaling by interfering with recruitment of MyD88 and TRIF.JImmunol 2012;188:4506-4515[PMID:22474023 DOI:10.4049/jimmunol.1200202]
91 Mueller T,Beutler C,PicóAH,Shibolet O,Pratt DS,Pascher A,Neuhaus P,Wiedenmann B,Berg T,Podolsky DK.Enhanced innate immune responsiveness and intolerance to intestinal endotoxins in human biliary epithelial cells contributes to chronic cholangitis.Liver Int 2011;31:1574-1588[PMID:22093333 DOI:10.1111/j.1478-3231.2011.02635.x]
92 Gao B,Seki E,Brenner DA,Friedman S,Cohen JI,Nagy L,Szabo G,Zakhari S.Innate immunity in alcoholic liver disease.Am J Physiol Gastrointest Liver Physiol 2011;300:G516-G525[PMID:21252049 DOI:10.1152/ajpgi.00537.2010]
93 Schroder K,Tschopp J.The inflammasomes.Cell 2010;140:821-832[PMID:20303873 DOI:10.1016/j.cell.2010.01.040]
94 Davis BK,Wen H,Ting JP.The inflammasome NLRs in immunity,inflammation,and associated diseases.Annu Rev Immunol 2011;29:707-735[PMID:21219188 DOI:10.1146/annurev-immunol-031210-101405]
95 Boaru SG,Borkham-Kamphorst E,Tihaa L,Haas U,Weiskirchen R.Expression analysis of inflammasomes in experimental models of inflammatory and fibrotic liver disease.J Inflamm(Lond)2012;9:49[PMID:23192004 DOI:10.1186/1476-9255-9-49]
96 Csak T,Ganz M,Pespisa J,Kodys K,Dolganiuc A,Szabo G.Fatty acid and endotoxin activate inflammasomes in mouse hepatocytes that release danger signals to stimulate immune cells.Hepatology 2011;54:133-144[PMID:21488066 DOI:10.1002/hep.24341]
97 Henao-Mejia J,Elinav E,Strowig T,Flavell RA.Inflammasomes:far beyond inflammation.Nat Immunol 2012;13:321-324[PMID:22430784 DOI:10.1038/ni.2257]
98 Martinon F,Mayor A,Tschopp J.The inflammasomes:guardians of the body.Annu Rev Immunol 2009;27:229-265[PMID:19302040]
99 Gurung P,Li B,Subbarao Malireddi RK,Lamkanfi M,Geiger TL,Kanneganti TD.Chronic TLR Stimulation Controls NLRP3Inflammasome Activation through IL-10 Mediated Regulation of NLRP3 Expression and Caspase-8 Activation.Sci Rep 2015;5:14488[PMID:26412089]
100 Chuang SY,Yang CH,Chou CC,Chiang YP,Chuang TH,Hsu LC.TLR-induced PAI-2 expression suppresses IL-1βprocessing via increasing autophagy and NLRP3 degradation.Proc Natl Acad Sci USA 2013;110:16079-16084[PMID:24043792DOI:10.1073/pnas.1306556110]
101 B?ckhed F,Ley RE,Sonnenburg JL,Peterson DA,Gordon JI.Host-bacterial mutualism in the human intestine.Science 2005;307:1915-1920[PMID:15790844 DOI:10.1126/science.1104816]
102 Johansson ME,Phillipson M,Petersson J,Velcich A,Holm L,Hansson GC.The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria.Proc Natl Acad Sci USA 2008;105:15064-15069[PMID:18806221 DOI:10.1073/pnas.0803124105]
103 Reunanen J,Kainulainen V,Huuskonen L,Ottman N,Belzer C,Huhtinen H,de Vos WM,Satokari R.Akkermansia muciniphila Adheres to Enterocytes and Strengthens the Integrity of the Epithelial Cell Layer.Appl Environ Microbiol2015;81:3655-3662[P M I D:25795669 D O I:10.1128/AEM.04050-14]
104赵凡,李春保.肠道菌Akkermansia muciniphila的特性及其与机体健康的关系.微生物学通报2017;6:1458-1463[DOI:10.13344/j.microbiol.china.160740]
105 Mukherjee S,Hooper LV.Antimicrobial defense of the intestine.Immunity 2015;42:28-39[PMID:25607457 DOI:10.1016/j.immuni.2014.12.028]
106 Kinnebrew MA,Ubeda C,Zenewicz LA,Smith N,Flavell RA,Pamer EG.Bacterial flagellin stimulates Toll-like receptor 5-dependent defense against vancomycin-resistant Enterococcus infection.J Infect Dis 2010;201:534-543[PMID:20064069 DOI:10.1086/650203]
107 Vaishnava S,Yamamoto M,Severson KM,Ruhn KA,Yu X,Koren O,Ley R,Wakeland EK,Hooper LV.The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine.Science 2011;334:255-258[PMID:21998396 DOI:10.1126/science.1209791]
108 Barreau F,Hugot JP.Intestinal barrier dysfunction triggered by invasive bacteria.Curr Opin Microbiol 2014;17:91-98[PMID:24440560 DOI:10.1016/j.mib.2013.12.003]
109 Epstein M,Wright JM.Severe multisystem disease caused by trimethoprim-sulfamethoxazole:possible role of an in vitro lymphocyte assay.J Allergy Clin Immunol 1990;86:416-417[PMID:2212414 DOI:10.1113/jphysiol.2011.219691]
110 Tan J,McKenzie C,Potamitis M,Thorburn AN,Mackay CR,Macia L.The role of short-chain fatty acids in health and disease.Adv Immunol 2014;121:91-119[PMID:24388214 DOI:10.1016/B978-0-12-800100-4.00003-9]
111 Lewis K,Lutgendorff F,Phan V,S?derholm JD,Sherman PM,Mc Kay DM.Enhanced translocation of bacteria across metabolically stressed epithelia is reduced by butyrate.Inflamm Bowel Dis 2010;16:1138-1148[PMID:20024905 DOI:10.1002/ibd.21177]
112 Arpaia N,Campbell C,Fan X,Dikiy S,van der Veeken J,deRoos P,Liu H,Cross JR,Pfeffer K,Coffer PJ,Rudensky AY.Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation.Nature 2013;504:451-455[PMID:24226773 DOI:10.1038/nature12726]
113 Singh N,Gurav A,Sivaprakasam S,Brady E,Padia R,Shi H,Thangaraju M,Prasad PD,Manicassamy S,Munn DH,Lee JR,Offermanns S,Ganapathy V.Activation of Gpr109a,receptor for niacin and the commensal metabolite butyrate,suppresses colonic inflammation and carcinogenesis.Immunity 2014;40:128-139[PMID:24412617 DOI:10.1016/j.immuni.2013.12.007]
114 Bordonaro M,Lazarova DL,Augenlicht LH,Sartorelli AC.Cell type-and promoter-dependent modulation of the Wnt signaling pathway by sodium butyrate.Int J Cancer 2002;97:42-51[PMID:11774242]
115 Zhang J,Yi M,Zha L,Chen S,Li Z,Li C,Gong M,Deng H,Chu X,Chen J,Zhang Z,Mao L,Sun S.Sodium Butyrate Induces Endoplasmic Reticulum Stress and Autophagy in Colorectal Cells:Implications for Apoptosis.PLoS One2016;11:e0147218[PMID:26784903 DOI:10.1371/journal.pone.0147218]
116 Madrigal-Matute J,Cuervo AM.Regulation of Liver Metabolism by Autophagy.Gastroenterology 2016;150:328-339[PMID:26453774 DOI:10.1053/j.gastro.2015.09.042]
117 Tang Y,Chen Y,Jiang H,Nie D.Short-chain fatty acids induced autophagy serves as an adaptive strategy for retarding mitochondria-mediated apoptotic cell death.Cell Death Differ 2011;18:602-618[PMID:20930850 DOI:10.1038/cdd.2010.117]
118 Czaja AJ.Targeting apoptosis in autoimmune hepatitis.Dig Dis Sci 2014;59:2890-2904[PMID:25038736 DOI:10.1007/s10620-014-3284-2]
119 Duncan SH,Louis P,Flint HJ.Lactate-utilizing bacteria,isolated from human feces,that produce butyrate as a major fermentation product.Appl Environ Microbiol 2004;70:5810-5817[PMID:15466518 DOI:10.1128/AEM.70.10.5810-5817.2004]
120 Vaarala O,Atkinson MA,Neu J.The“perfect storm”for type 1diabetes:the complex interplay between intestinal microbiota,gut permeability,and mucosal immunity.Diabetes 2008;57:2555-2562[PMID:18820210 DOI:10.2337/db08-0331]
121 Bourriaud C,Robins RJ,Martin L,Kozlowski F,Tenailleau E,Cherbut C,Michel C.Lactate is mainly fermented to butyrate by human intestinal microfloras but inter-individual variation is evident.J Appl Microbiol 2005;99:201-212[PMID:15960680DOI:10.1111/j.1365-2672.2005.02605.x]
122 Hov JR,Karlsen TH.The Microbiome in Primary Sclerosing Cholangitis:Current Evidence and Potential Concepts.Semin Liver Dis 2017;37:314-331[PMID:29272894 DOI:10.1055/s-0037-1608801]
123 Korkach VI,Prudnikov VM.Effect of corticotropin and hydrocortisone on the contractility and heat production of skeletal muscles.Fiziol Zh SSSR Im I M Sechenova 1977;63:1553-1557[PMID:201509 DOI:10.1155/2010/305879]
124 Li X,Wang C,Nie J,Lv D,Wang T,Xu Y.Toll-like receptor4 increases intestinal permeability through up-regulation of membrane PKC activity in alcoholic steatohepatitis.Alcohol 2013;47:459-465[PMID:23871536 DOI:10.1016/j.alcohol.2013.05.004]
125 Fasano A.Leaky gut and autoimmune diseases.Clin Rev Allergy Immunol 2012;42:71-78[PMID:22109896 DOI:10.1007/s12016-011-8291-x]
126 Chan ER,Hester J,Kalady M,Xiao H,Li X,Serre D.A novel method for determining microflora composition using dynamic phylogenetic analysis of 16S ribosomal RNA deep sequencing data.Genomics 2011;98:253-259[PMID:21515358DOI:10.1016/j.ygeno.2011.04.002]
127 Mandal RS,Saha S,Das S.Metagenomic surveys of gut microbiota.Genomics Proteomics Bioinformatics 2015;13:148-158[PMID:26184859 DOI:10.1016/j.gpb.2015.02.005]
128 Ma Y,Shi N,Li M,Chen F,Niu H.Applications of Nextgeneration Sequencing in Systemic Autoimmune Diseases.Genomics Proteomics Bioinformatics 2015;13:242-249[PMID:26432094 DOI:10.1016/j.gpb.2015.09.004]
129 Fraher MH,O’Toole PW,Quigley EM.Techniques used to characterize the gut microbiota:a guide for the clinician.Nat Rev Gastroenterol Hepatol 2012;9:312-322[PMID:22450307DOI:10.1038/nrgastro.2012.44]
130 Tottey W,Denonfoux J,Jaziri F,Parisot N,Missaoui M,Hill D,Borrel G,Peyretaillade E,Alric M,Harris HM,Jeffery IB,Claesson MJ,O’Toole PW,Peyret P,Brugère JF.The human gut chip“HuGChip”,an explorative phylogenetic microarray for determining gut microbiome diversity at family level.PLo SOne 2013;8:e62544[PMID:23690942 DOI:10.1371/journal.pone.0062544]
131 Eisen JA.Environmental shotgun sequencing:its potential and challenges for studying the hidden world of microbes.PLo S Biol 2007;5:e82[PMID:17355177 DOI:10.1371/journal.pbio.0050082]
132 Scaldaferri F,Lopetuso LR,Petito V,Cufino V,Bilotta M,Arena V,Stigliano E,Maulucci G,Papi M,Emiliana CM,Poscia A,Franceschi F,Delogu G,Sanguinetti M,Spirito MD,Sgambato A,Gasbarrini A.Gelatin tannate ameliorates acute colitis in mice by reinforcing mucus layer and modulating gut microbiota composition:Emerging role for‘gut barrier protectors’in IBD?United European Gastroenterol J 2014;2:113-122[PMID:24918016 DOI:10.1177/2050640614520867]
133 Bomhof MR,Parnell JA,Ramay HR,Crotty P,Rioux KP,Probert CS,Jayakumar S,Raman M,Reimer RA.Histological improvement of non-alcoholic steatohepatitis with a prebiotic:a pilot clinical trial.Eur J Nutr 2018[PMID:29779170 DOI:10.1007/s00394-018-1721-2]
134 Zhang W,Gu Y,Chen Y,Deng H,Chen L,Chen S,Zhang G,Gao Z.Intestinal flora imbalance results in altered bacterial translocation and liver function in rats with experimental cirrhosis.Eur J Gastroenterol Hepatol 2010;22:1481-1486[PMID:20739895 DOI:10.1097/MEG.0b013e32833eb8b0]
135 Nardone G,Compare D,Liguori E,Di Mauro V,Rocco A,Barone M,Napoli A,Lapi D,Iovene MR,Colantuoni A.Protective effects of Lactobacillus paracasei F19 in a rat model of oxidative and metabolic hepatic injury.Am JPhysiol Gastrointest Liver Physiol 2010;299:G669-G676[PMID:20576921 DOI:10.1152/ajpgi.00188.2010]
136 Tabibian JH,Weeding E,Jorgensen RA,Petz JL,Keach JC,Talwalkar JA,Lindor KD.Randomised clinical trial:vancomycin or metronidazole in patients with primary sclerosing cholangitis-a pilot study.Aliment Pharmacol Ther2013;37:604-612[PMID:23384404 DOI:10.1111/apt.12232]
137 Hommes DW,Erkelens W,Ponsioen C,Stokkers P,Rauws E,van der Spek M,ten Kate F,van Deventer SJ.A double-blind,placebo-controlled,randomized study of infliximab in primary sclerosing cholangitis.J Clin Gastroenterol 2008;42:522-526[PMID:18344886 DOI:10.1097/MCG.0b013e3181662426]
138 Cullen S N,Chapman R W.Reviewarticle:current management of primary sclerosing cholangitis.Aliment Pharmacol Ther 2005;21:933-948[PMID:15813829 DOI:10.1111/j.1365-2036.2005.02407.x]
139 Chapman R,Fevery J,Kalloo A,Nagorney DM,Boberg KM,Shneider B,Gores GJ;American Association for the Study of Liver Diseases.Diagnosis and management of primary sclerosing cholangitis.Hepatology 2010;51:660-678[PMID:20101749 DOI:10.1002/hep.23294]
140 Bj?ro K,Brandsaeter B,Foss A,Schrumpf E.Liver transplantation in primary sclerosing cholangitis.Semin Liver Dis 2006;26:69-79[PMID:16496235 DOI:10.1055/s-2006-933565]
141 Eaton JE,Talwalkar JA,Lazaridis KN,Gores GJ,Lindor KD.Pathogenesis of primary sclerosing cholangitis and advances in diagnosis and management.Gastroenterology 2013;145:521-536[PMID:23827861 DOI:10.1053/j.gastro.2013.06.052]