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《工程(英文)》 >> 2017年 第3卷 第1期 doi: 10.1016/J.ENG.2017.01.012

肠道不同解剖部位的菌群组成及其在结直肠癌中的作用

a Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong,Hong Kong, China
b Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, China

录用日期: 2017-02-01 发布日期: 2017-02-28

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摘要

结直肠癌是由遗传突变、表观遗传改变、慢性炎症、饮食和生活方式等多因素引起的多阶段疾病。最新研究表明,肠道菌群是结直肠癌发展过程中的重要参与者。肠道菌群稳态的失调,可通过诱发炎症、调控宿主防御、氧化应激和改变细菌代谢产物等机制促进结直肠癌的发生发展。值得注意的是,肠道横、纵截面上不同解剖部位的驻留菌群有所不同。根据细菌在肠道中定植部位的不同,可将其划分为4 种类型:肠腔共生菌、肠黏膜驻留菌、上皮驻留菌和淋巴组织驻留菌。由于结肠共生细菌的易位与结直肠癌的发展密切相关,结直肠癌相关细菌可有望成为用于结直肠癌诊断的非侵入且准确性高的新型生物标志物。本文旨在总结和概述肠道不同解剖部位中的肠道菌群在结直肠癌发生发展中的作用。

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参考文献

[ 1 ] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016;66(1):7–30 链接1

[ 2 ] Hou TY, Davidson LA, Kim E, Fan YY, Fuentes NR, Triff K, et alNutrient-gene interaction in colon cancer, from the membrane to cellular physiology. Annu Rev Nutr 2016;36:543–70 链接1

[ 3 ] Grady WM, Markowitz SD. Genetic and epigenetic alterations in colon cancer. Annu Rev Genom Hum G 2002;3(1):101–28 链接1

[ 4 ] Garrett WS. Cancer and the microbiota. Science 2015;348(6230):80–6 链接1

[ 5 ] Mima K, Nishihara R, Qian ZR, Cao Y, Sukawa Y, Nowak JA, et alFusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis. Gut. Epub 2015 Aug 26.

[ 6 ] Bhattacharya N, Yuan R, Prestwood TR, Penny HL, DiMaio MA, Reticker-Flynn NE, et alNormalizing microbiota-induced retinoic acid deficiency stimulates protective CD8 + T cell-mediated immunity in colorectal cancer. Immunity 2016;45(3):641–55 链接1

[ 7 ] Gur C, Ibrahim Y, Isaacson B, Yamin R, Abed J, Gamliel M, et alBinding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. Immunity 2015;42(2):344–55 链接1

[ 8 ] Brennan CA, Garrett WS. Gut microbiota, inflammation, and colorectal cancer. Annu Rev Microbiol 2016;70:395–411 链接1

[ 9 ] Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell 2014;157(1):121–41 链接1

[10] Arthur JC, Perez-Chanona E, Mühlbauer M, Tomkovich S, Uronis JM, Fan TJ, et alIntestinal inflammation targets cancer-inducing activity of the microbiota. Science 2012;338(6103):120–3 链接1

[11] Irrazábal T, Belcheva A, Girardin SE, Martin A, Philpott DJ. The multifaceted role of the intestinal microbiota in colon cancer. Mol Cell 2014;54(2):309–20 链接1

[12] Sears CL, Garrett WS. Microbes, microbiota, and colon cancer. Cell Host Microbe 2014;15(3):317–28 链接1

[13] Collins JW, Keeney KM, Crepin VE, Rathinam VAK, Fitzgerald KA, Finlay BB, et alCitrobacter rodentium: infection, inflammation and the microbiota. Nat Rev Microbiol 2014;12(9):612–23 链接1

[14] Chung HC, Pamp SJ, Hill JA, Surana NK, Edelman SM, Troy EB, et alGut immune maturation depends on colonization with a host-specific microbiota. Cell 2012;149(7):1578–93 链接1

[15] Duerkop BA, Vaishnava S, Hooper LV. Immune responses to the microbiota at the intestinal mucosal surface. Immunity 2009;31(3):368–76 链接1

[16] Geuking MB, Cahenzli J, Lawson MAE, Ng DCK, Slack E, Hapfelmeier S, et alIntestinal bacterial colonization induces mutualistic regulatory T cell responses. Immunity 2011;34(5):794–806 链接1

[17] Sellon RK, Tonkonogy S, Schultz M, Dieleman LA, Grenther W, Balish E, et alResident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect Immun 1998;66(11):5224–31.

[18] Zaiss MM, Rapin A, Lebon L, Dubey LK, Mosconi I, Sarter K, et alThe intestinal microbiota contributes to the ability of helminths to modulate allergic inflammation. Immunity 2015;43(5):998–1010 链接1

[19] Wang X, Yang Y, Moore DR, Nimmo SL, Lightfoot SA, Huycke MM. 4-hydroxy-2-nonenal mediates genotoxicity and bystander effects caused by Enterococcus faecalis-infected macrophages. Gastroenterology 2012;142(3):543–51 链接1

[20] Yang Y, Wang X, Huycke T, Moore DR, Lightfoot SA, Huycke MM. Colon macrophages polarized by commensal bacteria cause colitis and cancer through the bystander effect. Transl Oncol 2013;6(5):596–606 链接1

[21] Metzker ML. Sequencing technologies—the next generation. Nat Rev Genet 2010;11(1):31–46 链接1

[22] Schuster SC. Next-generation sequencing transforms today’s biology. Nat Methods 2008;5(1):16–8 链接1

[23] Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et alA human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010;464(7285):59–65 链接1

[24] Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol 2016;14(8):e1002533 链接1

[25] Evans DF, Pye G, Bramley R, Clark AG, Dyson TJ, Hardcastle JD. Measurement of gastrointestinal pH profiles in normal ambulant human subjects. Gut 1988;29(8):1035–41 链接1

[26] He G, Shankar RA, Chzhan M, Samouilov A, Kuppusamy P, Zweier JL. Noninvasive measurement of anatomic structure and intraluminal oxygenation in the gastrointestinal tract of living mice with spatial and spectral EPR imaging. Proc Natl Acad Sci USA 1999;96(8):4586–91 链接1

[27] Gallo RL, Hooper LV. Epithelial antimicrobial defence of the skin and intestine. Nat Rev Immunol 2012;12(7):503–16 链接1

[28] Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, et alRegulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 2009;461(7268):1282–6 链接1

[29] Rao SS, Kuo B, McCallum RW, Chey WD, DiBaise JK, Hasler WL, et alInvestigation of colonic and whole-gut transit with wireless motility capsule and radiopaque markers in constipation. Clin Gastroenterol Hepatol 2009;7(5):537–44 链接1

[30] Wlodarska M, Kostic AD, Xavier RJ. An integrative view of microbiome-host interactions in inflammatory bowel diseases. Cell Host Microbe 2015;17(5):577–91 链接1

[31] Bianconi E, Piovesan A, Facchin F, Beraudi A, Casadei R, Frabetti F, et alAn estimation of the number of cells in the human body. Ann Hum Biol 2013;40(6):463–71 链接1

[32] Chin KF, Kallam R, O’Boyle C, MacFie J. Bacterial translocation may influence the long-term survival in colorectal cancer patients. Dis Colon Rectum 2007;50(3):323–30 链接1

[33] Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, et alDiversity of the human intestinal microbial flora. Science 2005;308(5728):1635–8 链接1

[34] Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature 2012;489(7415):220–30 链接1

[35] Hill DA, Hoffmann C, Abt MC, Du Y, Kobuley D, Kirn TJ, et alMetagenomic analyses reveal antibiotic-induced temporal and spatial changes in intestinal microbiota with associated alterations in immune cell homeostasis. Mucosal Immunol 2010;3(2):148–58 链接1

[36] Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, et alEnterotypes of the human gut microbiome. Nature 2011;473(7346):174–80 链接1

[37] Nosho K, Sukawa Y, Adachi Y, Ito M, Mitsuhashi K, Kurihara H, et alAssociation of Fusobacterium nucleatum with immunity and molecular alterations in colorectal cancer. World J Gastroenterol 2016;22(2):557–66 链接1

[38] Abed J, Emg?rd JE, Zamir G, Faroja M, Almogy G, Grenov A, et alFap2 mediates Fusobacterium nucleatum colorectal adenocarcinoma enrichment by binding to tumor-expressed Gal-GalNAc. Cell Host Microbe 2016;20(2):215–25 链接1

[39] Huang JY, Lee SM, Mazmanian SK. The human commensal Bacteroides fragilis binds intestinal mucin. Anaerobe 2011;17(4):137–41 链接1

[40] Corfield AP. Mucins: a biologically relevant glycan barrier in mucosal protection. Bba-Gen Subjects 2015;1850(1):236–52 链接1

[41] Robertson BR, O’Rourke JL, Neilan BA, Vandamme P, On SLW, Fox JG, et alMucispirillum schaedleri gen. nov., sp nov., a spiral-shaped bacterium colonizing the mucus layer of the gastrointestinal tract of laboratory rodents. Int J Syst Evol Microbiol 2005;55(3):1199–204 链接1

[42] Li H, Limenitakis JP, Fuhrer T, Geuking MB, Lawson MA, Wyss M, et alThe outer mucus layer hosts a distinct intestinal microbial niche. Nat Commun 2015;6:8292 链接1

[43] Atarashi K, Tanoue T, Oshima K, Suda W, Nagano Y, Nishikawa H, et alTreg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 2013;500(7461):232–6 链接1

[44] Brook I, Myhal ML. Adherence of Bacteroides fragilis group species. Infect Immun 1991;59(2):742–4.

[45] Cossart P, Sansonetti PJ. Bacterial invasion: the paradigms of enteroinvasive pathogens. Science 2004;304(5668):242–8 链接1

[46] Martin HM, Campbell BJ, Hart CA, Mpofu C, Nayar M, Singh R, et alEnhanced Escherichia coli adherence and invasion in Crohn’s disease and colon cancer. Gastroenterology 2004;127(1):80–93 链接1

[47] Bonnet M, Buc E, Sauvanet P, Darcha C, Dubois D, Pereira B, et alColonization of the human gut by E. coli and colorectal cancer risk. Clin Cancer Res 2014;20(4):859–67 链接1

[48] Obata T, Goto Y, Kunisawa J, Sato S, Sakamoto M, Setoyama H, et alIndigenous opportunistic bacteria inhabit mammalian gut-associated lymphoid tissues and share a mucosal antibody-mediated symbiosis. Proc Natl Acad Sci USA 2010;107(16):7419–24 链接1

[49] Sonnenberg GF, Monticelli LA, Alenghat T, Fung TC, Hutnick NA, Kunisawa J, et alInnate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria. Science 2012;336(6086):1321–5 链接1

[50] Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, et alLinking long-term dietary patterns with gut microbial enterotypes. Science 2011;334(6052):105–8 链接1

[51] Corredoira J, Alonso MP, Coira A, Casariego E, Arias C, Alonso D, et alCharacteristics of Streptococcus bovis endocarditis and its differences with Streptococcus viridans endocarditis. Eur J Clin Microbiol Infect Dis 2008;27(4):285–91 链接1

[52] Lazarovitch T, Shango M, Levine M, Brusovansky R, Akins R, Hayakawa K, et alThe relationship between the new taxonomy of Streptococcus bovis and its clonality to colon cancer, endocarditis, and biliary disease. Infection 2013;41(2):329–37 链接1

[53] Gupta A, Madani R, Mukhtar H. Streptococcus bovis endocarditis, a silent sign for colonic tumour. Colorectal Dis 2010;12(3):164–71 链接1

[54] Harrison S, Benziger H, Koerner R. Streptococcus bovis infections, colorectal cancer and liver dysfunction. ANZ J Surg 2011;81(11):762–3 链接1

[55] McMahon AJ, Auld CD, Dale BA, Walls AD, McCormick JS. Streptococcus bovis septicaemia associated with uncomplicated colonic carcinoma. Br J Surg 1991;78(7):883–5 链接1

[56] Wending GK, Metzger PP, Dozois EJ, Chua HK, Krishna M. Unusual bacterial infections and colorectal carcinoma—Streptococcus bovis and Clostridium septicum: report of three cases. Dis Colon Rectum 2006;49(8):1223–7 链接1

[57] Klein RS, Catalano MT, Edberg SC, Casey JI, Steigbigel NH. Streptococcus bovis septicemia and carcinoma of the colon. Ann Intern Med 1979;91(4):560–2 链接1

[58] Boleij A, Roelofs R, Schaeps RM, Schülin T, Glaser P, Swinkels DW, et alIncreased exposure to bacterial antigen RpL7/L12 in early stage colorectal cancer patients. Cancer 2010;116(17):4014–22 链接1

[59] Ellmerich S, Sch?ller M, Duranton B, Gosse F, Galluser M, Klein JP, et alPromotion of intestinal carcinogenesis by Streptococcus bovis. Carcinogenesis 2000;21(4):753–6 链接1

[60] Tjalsma H, Sch?ller-Guinard M, Lasonder E, Ruers TJ, Willems HL, Swinkels DW. Profiling the humoral immune response in colon cancer patients: diagnostic antigens from Streptococcus bovis. Int J Cancer 2006;119(9):2127–35 链接1

[61] Biarc J, Nguyen IS, Pini A, Gosse F, Richert S, Thierse D, et alCarcinogenic properties of proteins with pro-inflammatory activity from Streptococcus infantarius (formerly S.bovis). Carcinogenesis 2004;25(8):1477–84 链接1

[62] Yu J, Feng Q, Wong SH, Zhang D, Liang QY, Qin Y, et alMetagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut 2017;66(1):70–8 链接1

[63] Kostic AD, Chun E, Robertson L, Glickman JN, Gallini CA, Michaud M, et alFusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 2013;14(2):207–15 链接1

[64] Tahara T, Yamamoto E, Suzuki H, Maruyama R, Chung W, Garriga J, et alFusobacterium in colonic flora and molecular features of colorectal carcinoma. Cancer Res 2014;74(5):1311–8 链接1

[65] Dharmani P, Strauss J, Ambrose C, Allen-Vercoe E, Chadee K. Fusobacteriumnucleatum infection of colonic cells stimulates MUC2 mucin and tumor necrosis factor alpha. Infect Immun 2011;79(7):2597–607 链接1

[66] Macfarlane S, Woodmansey EJ, Macfarlane GT. Colonization of mucin by human intestinal bacteria and establishment of biofilm communities in a two-stage continuous culture system. Appl Environ Microbiol 2005;71(11):7483–92 链接1

[67] Nakatsu G, Li X, Zhou H, Sheng J, Wong SH, Wu W, et alGut mucosal microbiome across stages of colorectal carcinogenesis. Nat Commun 2015;6:8727 链接1

[68] Chambers FG, Koshy SS, Saidi RF, Clark DP, Moore RD, Sears CL. Bacteroides fragilistoxin exhibits polar activity on monolayers of human intestinal epithelial cells (T84 cells) in vitro. Infect Immun 1997;65(9):3561–70.

[69] Wu S, Rhee KJ, Zhang M, Franco A, Sears CL. Bacteroides fragilis toxin stimulates intestinal epithelial cell shedding and gamma-secretase-dependent E-cadherin cleavage. J Cell Sci 2007;120:1944–52 链接1

[70] Soler AP, Miller RD, Laughlin KV, Carp NZ, Klurfeld DM, Mullin JM. Increased tight junctional permeability is associated with the development of colon cancer. Carcinogenesis 1999;20(8):1425–32 链接1

[71] Toprak NU, Yagci A, Gulluoglu BM, Akin ML, Demirkalem P, Celenk T, et alA possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer. Clin Microbiol Infect 2006;12(8):782–6 链接1

[72] Boleij A, Hechenbleikner EM, Goodwin AC, Badani R, Stein EM, Lazarev MG, et alThe Bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients. Clin Infect Dis 2015;60(2):208–15 链接1

[73] Sobhani I, Tap J, Roudot-Thoraval F, Roperch JP, Letulle S, Langella P, et alMicrobial dysbiosis in colorectal cancer (CRC) patients. PLoS One 2011;6(1):e16393 链接1

[74] Wang T, Cai G, Qiu Y, Fei N, Zhang M, Pang X, et alStructural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J 2012;6(2):320–9 链接1

[75] Goodwin AC, Destefano Shields CE, Wu S, Huso DL, Wu X, Murray-Stewart TR, et alPolyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis. Proc Natl Acad Sci USA 2011;108(37):15354–9. 10.1073/pnas.1010203108 链接1

[76] Housseau F, Sears CL. Enterotoxigenic Bacteroides fragilis (ETBF)-mediated colitis in Min (Apc+/?) mice: a human commensal-based murine model of colon carcinogenesis. Cell Cycle 2010;9(1):3–5 链接1

[77] Ubeda C, Taur Y, Jenq RR, Equinda MJ, Son T, Samstein M, et alVancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans. J Clin Invest 2010;120(12):4332–41 链接1

[78] Sonnenburg JL, Chen CT, Gordon JI. Genomic and metabolic studies of the impact of probiotics on a model gut symbiont and host. PLoS Biol 2006;4(12):e413 链接1

[79] Thompson-Chagoyán OC, Maldonado J, Gil A. Aetiology of inflammatory bowel disease (IBD): role of intestinal microbiota and gut-associated lymphoid tissue immune response. Clin Nutr 2005;24(3):339–52 链接1

[80] Corr SC, Li Y, Riedel CU, O’Toole PW, Hill C, Gahan CG. Bacteriocin production as a mechanism for the antiinfective activity of Lactobacillus salivarius UCC118. Proc Natl Acad Sci USA 2007;104(18):7617–21 链接1

[81] Dunne C, Murphy L, Flynn S, O’Mahony L, O’Halloran S, Feeney M, et alProbiotics: from myth to reality. Demonstration of functionality in animal models of disease and in human clinical trials. Antonie van Leeuwenhoek 1999;76(1):279–92 链接1

[82] Johansson MEV, Gustafsson JK, Holmén-Larsson J, Jabbar KS, Xia L, Xu H, et alBacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis. Gut 2014;63(2):281–91 链接1

[83] Johansson MEV, 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(39):15064–9 链接1

[84] Johansson MEV, Hansson GC. Immunological aspects of intestinal mucus and mucins. Nat Rev Immunol 2016;16(10):639–49 链接1

[85] Johansson ME, Jakobsson HE, Holmén-Larsson J, Schütte A, Ermund A, Rodriguez-Pi?eiro AM, et alNormalization of host intestinal mucus layers requires long-term microbial colonization. Cell Host Microbe 2015;18(5):582–92 链接1

[86] Johansson MEV. Fast renewal of the distal colonic mucus layers by the surface goblet cells as measured by in vivo labeling of mucin glycoproteins. PLoS One 2012;7(7):e41009 链接1

[87] Jakobsson HE, Rodríguez-Pi?eiro AM, Schütte A, Ermund A, Boysen P, Bemark M, et alThe composition of the gut microbiota shapes the colon mucus barrier. EMBO Rep 2015;16(2):164–77 链接1

[88] Derrien M, Collado MC, Ben-Amor K, Salminen S, de Vos WM. The mucin degrader Akkermansia muciniphila is an abundant resident of the human intestinal tract. Appl Environ Microbiol 2008;74(5):1646–8 链接1

[89] Peterson LW, Artis D. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat Rev Immunol 2014;14(3):141–53 链接1

[90] Yang Q, Bermingham NA, Finegold MJ, Zoghbi HY. Requirement of Math1 for secretory cell lineage commitment in the mouse intestine. Science 2001;294(5549):2155–8 链接1

[91] Gaboriau-Routhiau V, Rakotobe S, Lécuyer E, Mulder I, Lan A, Bridonneau C, et alThe key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 2009;31(4):677–89 链接1

[92] Rolhion N, Darfeuille-Michaud A. Adherent-invasive Escherichia coli in inflammatory bowel disease. Inflamm Bowel Dis 2007;13(10):1277–83 链接1

[93] Baumgart M, Dogan B, Rishniw M, Weitzman G, Bosworth B, Yantiss R, et alCulture independent analysis of ileal mucosa reveals a selective increase in invasive Escherichia coli of novel phylogeny relative to depletion of Clostridiales in Crohn’s disease involving the ileum. ISME J 2007;1(5):403–18 链接1

[94] Swidsinski A, Khilkin M, Kerjaschki D, Schreiber S, Ortner M, Weber J, et alAssociation between intraepithelial Escherichia coli and colorectal cancer. Gastroenterology 1998;115(2):281–6 链接1

[95] Dreux N, Denizot J, Martinez-Medina M, Mellmann A, Billig M, Kisiela D, et alPoint mutations in FimH adhesin of Crohn’s disease-associated adherent-invasive Escherichia coli enhance intestinal inflammatory response. PLoS Pathog 2013;9(1):e1003141 链接1

[96] Eaves-Pyles T, Allen CA, Taormina J, Swidsinski A, Tutt CB, Jezek GE, et alEscherichia coli isolated from a Crohn’s disease patient adheres, invades, and induces inflammatory responses in polarized intestinal epithelial cells. Int J Med Microbiol 2008;298(5–6):397–409 链接1

[97] Subramanian S, Rhodes JM, Hart CA, Tam B, Roberts CL, Smith SL, et alCharacterization, of epithelial IL8 response to inflammatory bowel disease mucosal E. coli and its inhibition by mesalamine. Inflamm Bowel Dis 2008;14(2):162–75 链接1

[98] Mimouna S, Goncalves D, Barnich N, Darfeuille-Michaud A, Hofman P, Vouret-Craviari V. Crohn disease-associated Escherichia coli promote gastrointestinal inflammatory disorders by activation of HIF-dependent responses. Gut Microbes 2011;2(6):335–46 链接1

[99] Hoesel B, Schmid JA. The complexity of NF-κB signaling in inflammation and cancer. Mol Cancer 2013;12(1):86 链接1

[100] Mcwilliams M, Phillips-Quagliata JM, Lamm ME. Characteristics of mesenteric lymph-node cells homing to gut-associated lymphoid-tissue in syngeneic mice. J Immunol 1975;115(1):54–8.

[101] Kunisawa J, Kiyono H. Alcaligenes is commensal bacteria habituating in the gut-associated lymploid tissue for the regulation of intestinal IgA responses. Front Immunol 2012;3:65 链接1

[102] Fung TC, Bessman NJ, Hepworth MR, Kumar N, Shibata N, Kobuley D, et alLymphoid-tissue-resident commensal bacteria promote members of the IL-10 cytokine family to establish mutualism. Immunity 2016;44(3):634–46 链接1

[103] Beaugerie L, Itzkowitz SH. Cancers complicating inflammatory bowel disease. N Engl J Med 2015;372(15):1441–52 链接1

[104] Deitch EA. Bacterial translocation or lymphatic drainage of toxic products from the gut: what is important in human beings? Surgery 2002;131(3):241–4 链接1

[105] Grivennikov SI, Wang K, Mucida D, Stewart CA, Schnabl B, Jauch D, et alAdenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 2012;491(7423):254–8 链接1

[106] Elinav E, Nowarski R, Thaiss CA, Hu B, Jin CC, Flavell RA. Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer 2013;13(11):759–71 链接1

[107] Karin M, Greten FR. NF-κB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol 2005;5(10):749–59 链接1

[108] Liang J, Nagahashi M, Kim EY, Harikumar KB, Yamada A, Huang W, et alSphingosine-1-phosphate links persistent STAT3 activation, chronic intestinal inflammation, and development of colitis-associated cancer. Cancer Cell 2013;23(1):107–20 链接1

[109] Madia F, Grossi V, Peserico A, Simone C. Updates from the intestinal front line: autophagic weapons against inflammation and cancer. Cells 2012;1(3):535–57 链接1

[110] Vannucci L, Stepankova R, Kozakova H, Fiserova A, Rossmann P, Tlaskalova-Hogenova H. Colorectal carcinogenesis in germ-free and conventionally reared rats: different intestinal environments affect the systemic immunity. Int J Oncol 2008;32(3):609–17 链接1

[111] Li Y, Kundu P, Seow SW, de Matos CT, Aronsson L, Chin KC, et alG ut microbiota accelerate tumor growth via c-jun and STAT3 phosphorylation in APCMin/+ mice. Carcinogenesis 2012;33(6):1231–8 链接1

[112] Louis P, Hold GL, Flint HJ. The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev Microbiol 2014;12(10):661–72 链接1

[113] Ou J, Carbonero F, Zoetendal EG, DeLany JP, Wang M, Newton K, et alDiet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans. Am J Clin Nutr 2013;98(1):111–20. 10.3945/ajcn.112.056689 链接1

[114] Russell WR, Gratz SW, Duncan SH, Holtrop G, Ince J, Scobbie L, et alHigh-protein, reduced-carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health. Am J Clin Nutr 2011;93(5):1062–72 链接1

[115] Loh YH, Jakszyn P, Luben RN, Mulligan AA, Mitrou PN, Khaw KT. N-nitroso compounds and cancer incidence: the European Prospective Investigation into Cancer and Nutrition (EPIC)- Norfolk Study. Am J Clin Nutr 2011;93(5):1053–61 链接1

[116] Windey K, De Preter V, Verbeke K. Relevance of protein fermentation to gut health. Mol Nutr Food Res 2012;56(1):184–96 链接1

[117] Marquet P, Duncan SH, Chassard C, Bernalier-Donadille A, Flint HJ. Lactate has the potential to promote hydrogen sulphide formation in the human colon. FEMS Microbiol Lett 2009;299(2):128–34 链接1

[118] Roediger WE, Moore J, Babidge W. Colonic sulfide in pathogenesis and treatment of ulcerative colitis. Dig Dis Sci 1997;42(8):1571–9 链接1

[119] Di Martino ML, Campilongo R, Casalino M, Micheli G, Colonna B, Prosseda G. Polyamines: emerging players in bacteria-host interactions. Int J Med Microbiol 2013;303(8):484–91 链接1

[120] Pegg AE. Toxicity of polyamines and their metabolic products. Chem Res Toxicol 2013;26(12):1782–800 链接1

[121] Wiseman M. The second World Cancer Research Fund/American Institute for Cancer Research expert report. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. Proc Nutr Soc 2008;67(3):253–6 链接1

[122] Homann N. Alcohol and upper gastrointestinal tract cancer: the role of local acetaldehyde production. Addict Biol 2001;6(4):309–23 链接1

[123] Lescut D, Colombel JF, Vincent P, Cortot A, Fournier L, Quandalle P, et alBacterial translocation in colorectal cancers. Gastroenterol Clin Biol 1990;14(11):811–4.

[124] Klein GL, Petschow BW, Shaw AL, Weaver E. Gut barrier dysfunction and microbial translocation in cancer cachexia: a new therapeutic target. Curr Opin Support Palliat Care 2013;7(4):361–7 链接1

[125] Liang JQ, Chiu J, Chen Y, Huang Y, Higashimori A, Fang JY, et alFecal bacteria act as novel biomarkers for non-invasive diagnosis of colorectal cancer. Clin Cancer Res. Epub 2016 Oct 3 链接1

[126] Wong SH, Kwong TN, Chow TC, Luk AK, Dai RZ, Nakatsu G, et alQuantitation of faecal Fusobacterium improves faecal immunochemical test in detecting advanced colorectal neoplasia. Gut. Epub 2016 Oct 24 链接1

[127] Wei Z, Cao S, Liu S, Yao Z, Sun T, Li Y, et alCould gut microbiota serve as prognostic biomarker associated with colorectal cancer patients’ survival? A pilot study on relevant mechanism. Oncotarget 2016;7(29):46158–72.

[128] Rubinstein MR, Wang X, Liu W, Hao Y, Cai G, Han YW. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin. Cell Host Microbe 2013;14(2):195–206 链接1

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