Microbiome and colorectal carcinoma: Insights from germ-free and conventional animal models

Cancer Journal (United States)

Volumn 20, Issue 3, 2014, Pages 217-224

  Tlaskalova Hogenova, Helena ^a,b   Vannucci, Luca ^a   Klimesova, Klara ^a,c   Stepankova, Renata ^a   Krizan, Jiri ^a   Kverka, Miloslav ^a  

^a INSTITUTE OF MICROBIOLOGY   (Czech Republic)

^b CHARLES UNIVERSITY   (Czech Republic)

^c UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

Author keywords

carcinogens; colorectal cancer; germ free animals; inflammation; inflammatory bowel diseases; microbiome; Microbiota; mucosal immunity; probiotics; tumor microenvironment

Indexed keywords

CARCINOGEN; CYTOSTATIC AGENT; ESSENTIAL AMINO ACID; ESTERASE; GAMMA INTERFERON; GLYCOSIDASE; INFLAMMASOME; INTERLEUKIN 10; INTERLEUKIN 17; INTERLEUKIN 22; INTERLEUKIN 23; INTERLEUKIN 6; PATTERN RECOGNITION RECEPTOR; POLYSACCHARIDE; PREBIOTIC AGENT; PROBIOTIC AGENT; REACTIVE OXYGEN METABOLITE; SHORT CHAIN FATTY ACID; STAT3 PROTEIN; SYNBIOTIC AGENT; TUMOR NECROSIS FACTOR ALPHA; VITAMIN;

ANGIOGENESIS; ANIMAL MODEL; ANTIBIOTIC THERAPY; APOPTOSIS; BACTEROIDES FRAGILIS; BACTEROIDETES; CARCINOGENESIS; CELL DIFFERENTIATION; CELL PROLIFERATION; CHRONIC INFLAMMATION; COLITIS; COLORECTAL ADENOMA; COLORECTAL CARCINOMA; COMMENSAL; COMMENSAL ESCHERICHIA COLI; DIABETES MELLITUS; DIETARY FIBER; DIETARY INTAKE; DYSBIOSIS; ENTEROCOCCUS FAECALIS; EUBACTERIUM; FAECALIBACTERIUM PRAUSNITZII; FERMENTATION; FIRMICUTES; FUSOBACTERIUM NUCLEATUM; GENE INACTIVATION; GENE TARGETING; GENOTOXICITY; GERMFREE ANIMAL; GNOTOBIOTICS; HELICOBACTER PYLORI; HUMAN; INFLAMMATION; INFLAMMATORY BOWEL DISEASE; INTESTINE FLORA; INTESTINE MUCOSA; LACTOBACILLUS ACIDOPHILUS; MICROBIOME; MUCOSAL IMMUNITY; NONHUMAN; PRIORITY JOURNAL; PROTEOBACTERIA; REVIEW; ROSEBURIA; TRANSGENIC ANIMAL; TUMOR MICROENVIRONMENT; ANIMAL; COLORECTAL TUMOR; DISEASE MODEL; MICROBIOLOGY; MICROFLORA;

ANIMALS; COLORECTAL NEOPLASMS; DISEASE MODELS, ANIMAL; GERM-FREE LIFE; HUMANS; INFLAMMATION; MICROBIOTA; TUMOR MICROENVIRONMENT;

EID: 84901503024     PISSN: 15289117     EISSN: 1540336X     Source Type: Journal    
DOI: 10.1097/PPO.0000000000000052     Document Type: Review

References (123)

1. Lagier JC, Armougom F, Million M, et al. Microbial culturomics: paradigm shift in the human gut microbiome study. Clin Microbiol Infect. 2012;18;1185-1193.
2. Hooper LV, Wong MH, Thelin A, et al. Molecular analysis of commensal host-microbial relationships in the intestine. Science 2001;291;881-884. (Pubitemid 32120760)
3. Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010;464;59-65.
4. Lozupone CA, Stombaugh JI, Gordon JI, et al. Diversity, stability and resilience of the human gut microbiota. Nature 2012;489;220-230.
5. Plottel CS, Blaser MJ. Microbiome and malignancy. Cell Host Microbe. 2011;10;324-335 6.
6. Sommer F, Backhed F. The gut microbiota-masters of host development and physiology. Nat Rev Microbiol. 2013;11;227-238.
7. Tlaskalova-Hogenova H, Stepankova R, Hudcovic T, et al. Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases. Immunol Lett. 2004;93;97-108. (Pubitemid 38678650)
8. Falk PG, Hooper LV, Midtvedt T, et al. Creating and maintaining the gastrointestinal ecosystem: what we know and need to know from gnotobiology. Microbiol Mol Biol Rev. 1998;62;1157-1170. (Pubitemid 28558295)
9. Faith JJ, Rey FE, O'Donnell D, et al. Creating and characterizing communities of human gut microbes in gnotobiotic mice. ISME J. 2010;4; 1094-1098.
10. Tlaskalova-Hogenova H, Stepankova R, Kozakova H, et al. The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases. Cell Mol Immunol. 2011;8;110-120.
11. Cebra JJ, Jiang H-Q, Boiko N, et al. The role of mucosal microbiota in the development, maintenance, and pathologies of the mucosal immune system. In: Mestecky J, Bienenstock J, Lamm ME, et al., eds. Mucosal Immunology. 3rd ed. Amsterdam, The Netherlands: Elsevier-Academic Press; 2005:335-368.
12. Inzunza J, Midtvedt T, Fartoo M, et al. Germfree status of mice obtained by embryo transfer in an isolator environment. Lab Anim. 2005;39; 421-427. (Pubitemid 41565463)
13. Tlaskalova-Hogenova H, Sterzl J. Gnotobiological models. In: Lefkovits I, ed. Immunology Methods Manual: The Comprehensive Sourcebook of Techniques. 1st ed. San Diego, CA: Academic Press; 1997:1521-1561.
14. Packey CD, Shanahan MT, Manick S, et al. Molecular detection of bacterial contamination in gnotobiotic rodent units. Gut Microbes. 2013;4.
15. Arthur JC, Jobin C. The struggle within: microbial influences on colorectal cancer. Inflamm Bowel Dis. 2011;17;396-409.
16. Wen L, Ley RE, Volchkov PY, et al. Innate immunity and intestinal microbiota in the development of type 1 diabetes. Nature 2008;455;1109-1113.
17. Marchesi JR, Dutilh BE, Hall N, et al. Towards the human colorectal cancer microbiome. PLoS One 2011;6;e20447.
18. Shen XJ, Rawls JF, Randall T, et al. Molecular characterization of mucosal adherent bacteria and associations with colorectal adenomas. Gut Microbes. 2010;1;138-147.
19. Ahn J, Sinha R, Pei Z, et al. Human gut microbiome and risk for colorectal cancer. J Natl Cancer Inst. 2013;105;1907-1911.
20. Kostic AD, Chun E, Robertson L, et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe. 2013;14;207-215.
21. Kumar M, Nagpal R, Verma V, et al. Probiotic metabolites as epigenetic targets in the prevention of colon cancer. Nutr Rev. 2013;71;23-34.
22. Hirayama A, Kami K, Sugimoto M, et al. Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry. Cancer Res. 2009;69;4918-4925.
23. Tanaka T, Kohno H, Suzuki R, et al. A novel inflammation-related mouse colon carcinogenesis model induced by azoxymethane and dextran sodium sulfate. Cancer Sci. 2003;94;965-973. (Pubitemid 37508979)
24. Vannucci L, Huggins CB, Mosca F. A new experimental model for colorectal carcinogenesis in the rat. J Environ Pathol Toxicol Oncol. 1994;13;59-61. (Pubitemid 24273450)
25. Goldin BR, Gorbach SL. Alterations of the intestinal microflora by diet, oral antibiotics, and Lactobacillus: decreased production of free amines from aromatic nitro compounds, azo dyes, and glucuronides. J Natl Cancer Inst. 1984;73;689-695. (Pubitemid 14000202)
26. Fiala E. Investigations into the metabolism and mode of action of the colon carcinogen 1, 2-dimethylhydrazine. Cancer 1975;36;2407-2412.
27. Vannucci L, Stepankova R, Kozakova H, et al. Colorectal carcinogenesis in germ-free and conventionally reared rats: different intestinal environments affect the systemic immunity. Int J Oncol. 2008;32;609-617. (Pubitemid 351330467)
28. Klimesova K, Kverka M, Zakostelska Z, et al. Altered gut microbiota promotes colitis-associated cancer in IL-1 receptor-associated kinase M-deficient mice. Inflamm Bowel Dis. 2013;19;1266-1277.
29. Sayin SI, Wahlstrom A, Felin J, et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab. 2013;17;225-235.
30. Tlaskalova-Hogenova H, Sterzl J, Stepankova R, et al. Development of immunological capacity under germfree and conventional conditions. Ann N Y Acad Sci. 1983;409;96-113. (Pubitemid 13057638)
31. Hansen CH, Nielsen DS, Kverka M, et al. Patterns of early gut colonization shape future immune responses of the host. PLoS One 2012;7; e34043.
32. Narushima S, Itoh K, Mitsuoka T, et al. Effect ofmouse intestinal bacteria on incidence of colorectal tumors induced by 1,2-dimethylhydrazine injection in gnotobiotic transgenic mice harboring human prototype c-Ha-ras genes. Exp Anim. 1998;47;111-117. (Pubitemid 128439299)
33. Reddy BS,Watanabe K. Effect of intestinal microflora on 2,2'-dimethyl-4-aminobiphenyl-induced carcinogenesis in F344 rats.J NatlCancer Inst. 1978;61;1269-1271.
34. Uronis JM, Muhlbauer M, Herfarth HH, et al. Modulation of the intestinal microbiota alters colitis-associated colorectal cancer susceptibility. PLoS One 2009;4;e6026.
35. Vannucci L, Stepankova R, Grobarova V, et al. Colorectal carcinoma: Importance of colonic environment for anti-cancer response and systemic immunity. J Immunotoxicol. 2009;6;217-226.
36. Huycke MM, Abrams V, Moore DR. Enterococcus faecalis produces extracellular superoxide and hydrogen peroxide that damages colonic epithelial cell DNA. Carcinogenesis 2002;23;529-536. (Pubitemid 34257634)
37. Arthur JC, Perez-Chanona E,Muhlbauer M, et al. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 2012;338;120-123.
38. McCoy AN, Araujo-Perez F, Azcarate-Peril A, et al. Fusobacterium is associated with colorectal adenomas. PLoS One 2013;8;e53653.
39. Strauss J, Kaplan GG, Beck PL, et al. Invasive potential of gut mucosaderived Fusobacterium nucleatum positively correlates with IBD status of the host. Inflamm Bowel Dis. 2011;17;1971-1978.
40. Wu S, Rhee KJ, Albesiano E, et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med. 2009;15;1016-1022.
41. Darfeuille-Michaud A, Boudeau J, Bulois P, et al. High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease. Gastroenterology 2004;127;412-421. (Pubitemid 39091889)
42. Stepankova R, Powrie F, Kofronova O, et al. Segmented filamentous bacteria in a defined bacterial cocktail induce intestinal inflammation in SCID mice reconstituted with CD45RBhigh CD4+ T cells. Inflamm Bowel Dis. 2007;13;1202-1211. (Pubitemid 47597767)
43. Davis CD, Milner JA. Gastrointestinal microflora, food components and colon cancer prevention. J Nutr Biochem. 2009;20;743-752.
44. Hrncir T, Stepankova R, Kozakova H, et al. Gut microbiota and lipopolysaccharide content of the diet influence development of regulatory T cells: studies in germ-free mice. BMC Immunol. 2008;9;65.
45. Candela M, Turroni S, Biagi E, et al. Inflammation and colorectal cancer, when microbiota-host mutualism breaks. World J Gastroenterol. 2014;20;908-922.
46. Mykkanen H, Tikka J, Pitkanen T, et al. Fecal bacterial enzyme activities in infants increase with age and adoption of adult-type diet. J Pediatr Gastroenterol Nutr. 1997;25;312-316. (Pubitemid 27375423)
47. David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014;505;559-563.
48. Zoetendal EG, de Vos WM. Effect of diet on the intestinal microbiota and its activity. Curr Opin Gastroenterol. 2014;30;189-195.
49. Wang D, DuBois RN. An inflammatory mediator, prostaglandin E2, in colorectal cancer. Cancer J. 2013;19;502-510.
50. Larsson SC, Wolk A. Meat consumption and risk of colorectal cancer: a meta-analysis of prospective studies. Int J Cancer 2006;119;2657-2664. (Pubitemid 44691322)
51. Reddy BS, Narisawa T, Weisburger JH. Effect of a diet with high levels of protein and fat on colon carcinogenesis in F344 rats treated with 1,2-dimethylhydrazine. J Natl Cancer Inst. 1976;57;567-569.
52. Cross AJ, Pollock JR, Bingham SA. Haem, not protein or inorganic iron, is responsible for endogenous intestinal N-nitrosation arising from red meat. Cancer Res. 2003;63;2358-2360. (Pubitemid 36605167)
53. Macfarlane GT, Macfarlane S. Bacteria, colonic fermentation, and gastrointestinal health. J AOAC Int. 2012;95;50-60.
54. Calmels S, Ohshima H, Henry Y, et al. Characterization of bacterial cytochrome cd(1)-nitrite reductase as one enzyme responsible for catalysis of nitrosation of secondary amines. Carcinogenesis 1996;17;533-536. (Pubitemid 26085334)
55. Lewin MH, Bailey N, Bandaletova T, et al. Red meat enhances the colonic formation of the DNA adduct O6-carboxymethyl guanine: implications for colorectal cancer risk. Cancer Res. 2006;66;1859-1865. (Pubitemid 43259973)
56. Attene-Ramos MS, Wagner ED, Gaskins HR, et al. Hydrogen sulfide induces direct radical-associated DNA damage. Mol Cancer Res. 2007;5;455-459. (Pubitemid 46903954)
57. Ramasamy S, Singh S, Taniere P, et al. Sulfide-detoxifying enzymes in the human colon are decreased in cancer and upregulated in differentiation. Am J Physiol Gastrointest Liver Physiol. 2006;291;G288-G296. (Pubitemid 44024689)
58. Dabek M, McCrae SI, Stevens VJ, et al. Distribution of betaglucosidase and beta-glucuronidase activity and of beta-glucuronidase gene gus in human colonic bacteria. FEMS Microbiol Ecol. 2008;66; 487-495.
59. Gadelle D, Raibaud P, Sacquet E. beta-Glucuronidase activities of intestinal bacteria determined both in vitro and in vivo in gnotobiotic rats. Appl Environ Microbiol. 1985;49;682-685. (Pubitemid 15138062)
60. Gloux K, Berteau O, El Oumami H, et al. A metagenomic betaglucuronidase uncovers a core adaptive function of the human intestinal microbiome. Proc Natl Acad Sci USA. 2011;108(suppl 1);4539-4546.
61. Carman RJ, Van Tassell RL, Kingston DG, et al. Conversion of IQ, a dietary pyrolysis carcinogen to a direct-acting mutagen by normal intestinal bacteria of humans. Mutat Res. 1988;206;335-342.
62. Wu T, Zhang Z, Liu B, et al. Gut microbiota dysbiosis and bacterial community assembly associated with cholesterol gallstones in largescale study. BMC Genomics. 2013;14;669.
63. Duboc H, Rajca S, Rainteau D, et al. Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut. 2013;62;531-539.
64. Murphy N, Norat T, Ferrari P, et al. Dietary fibre intake and risks of cancers of the colon and rectum in the European prospective investigation into cancer and nutrition (EPIC). PLoS One 2012;7;e39361.
65. Gill SR, Pop M, Deboy RT, et al. Metagenomic analysis of the human distal gut microbiome. Science 2006;312;1355-1359. (Pubitemid 43839542)
66. Fung KY, Cosgrove L, Lockett T, et al. A review of the potential mechanisms for the lowering of colorectal oncogenesis by butyrate. Br J Nutr. 2012;108;820-831.
67. Singh N, Gurav A, Sivaprakasam S, et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 2014;40;128-139.
68. Louis P, Young P, Holtrop G, et al. Diversity of human colonic butyrateproducing bacteria revealed by analysis of the butyryl-CoA:acetate CoA-transferase gene. Environ Microbiol. 2010;12;304-314.
69. Canani RB, Costanzo MD, Leone L, et al. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J Gastroenterol. 2011;17;1519-1528.
70. Leng SL, Leeding KS, Gibson PR, et al. Insulin-like growth factor-II renders LIM 2405 human colon cancer cells resistant to butyrateinduced apoptosis: a potential mechanism for colon cancer cell survival in vivo. Carcinogenesis 2001;22;1625-1631. (Pubitemid 32952139)
71. Mandal M, Wu X, Kumar R. Bcl-2 deregulation leads to inhibition of sodium butyrate-induced apoptosis in human colorectal carcinoma cells. Carcinogenesis 1997;18;229-232. (Pubitemid 28134638)
72. Scharlau D, Borowicki A, Habermann N, et al. Mechanisms of primary cancer prevention by butyrate and other products formed during gut floramediated fermentation of dietary fibre. Mutat Res. 2009;682;39-53.
73. Bordonaro M, Lazarova DL, Sartorelli AC. Butyrate and Wnt signaling: a possible solution to the puzzle of dietary fiber and colon cancer risk? Cell Cycle. 2008;7;1178-1183. (Pubitemid 351749270)
74. Ishikawa H, Akedo I, Otani T, et al. Randomized trial of dietary fiber and Lactobacillus casei administration for prevention of colorectal tumors. Int J Cancer 2005;116;762-767. (Pubitemid 41099707)
75. Rafter J, Bennett M, Caderni G, et al. Dietary synbiotics reduce cancer risk factors in polypectomized and colon cancer patients. Am J Clin Nutr. 2007;85;488-496. (Pubitemid 46220953)
76. Capurso G, Marignani M, Delle Fave G. Probiotics and the incidence of colorectal cancer: when evidence is not evident. Dig Liver Dis. 2006;38(Suppl 2);S277-S282. (Pubitemid 46140769)
77. Worthley DL, Le Leu RK, Whitehall VL, et al. A human, double-blind, placebo-controlled, crossover trial of prebiotic, probiotic, and synbiotic supplementation: effects on luminal, inflammatory, epigenetic, and epithelial biomarkers of colorectal cancer. Am J Clin Nutr. 2009;90; 578-586.
78. Arthur JC, Gharaibeh RZ, Uronis JM, et al. VSL#3 probiotic modifies mucosal microbial composition but does not reduce colitis-associated colorectal cancer. Sci Rep. 2013;3;2868.
79. Chong ES. A potential role of probiotics in colorectal cancer prevention: review of possible mechanisms of action. World J Microbiol Biotechnol. 2014;30;351-374.
80. Carroll IM, Andrus JM, Bruno-Barcena JM, et al. Anti-inflammatory properties of Lactobacillus gasseri expressing manganese superoxide dismutase using the interleukin 10-deficient mouse model of colitis. Am J Physiol Gastrointest Liver Physiol. 2007;293;G729-G738. (Pubitemid 47605922)
81. Motta JP, Bermudez-Humaran LG, Deraison C, et al. Food-grade bacteria expressing elafin protect against inflammation and restore colon homeostasis. Sci Transl Med. 2012;4;158ra144.
82. Mohamadzadeh M, Pfeiler EA, Brown JB, et al. Regulation of induced colonic inflammation by Lactobacillus acidophilus deficient in lipoteichoic acid. Proc Natl Acad Sci USA. 2011;108(Suppl 1); 4623-4630.
83. Khazaie K, Zadeh M, Khan MW, et al. Abating colon cancer polyposis by Lactobacillus acidophilus deficient in lipoteichoic acid. Proc Natl Acad Sci USA. 2012;109;10462-10467.
84. Wehkamp J, Harder J, Wehkamp K, et al. NF-kappaB-and AP-1-mediated induction of human beta defensin-2 in intestinal epithelial cells by Escherichia coli Nissle 1917: a novel effect of a probiotic bacterium. Infect Immun. 2004;72;5750-5758. (Pubitemid 39303685)
85. Konstantinov SR, Smidt H, de Vos WM, et al. S layer protein A of Lactobacillus acidophilus NCFM regulates immature dendritic cell and T cell functions. Proc Natl Acad Sci USA. 2008;105; 19474-19479.
86. Mondel M, Schroeder BO, Zimmermann K, et al. Probiotic E. coli treatment mediates antimicrobial human beta-defensin synthesis and fecal excretion in humans. Mucosal Immunol. 2009;2;166-172.
87. Zakostelska Z, Kverka M, Klimesova K, et al. Lysate of probiotic Lactobacillus casei DN-114 001 ameliorates colitis by strengthening the gut barrier function and changing the gut microenvironment. PLoS One 2011;6;e27961.
88. Kverka M, Zakostelska Z, Klimesova K, et al. Oral administration of Parabacteroides distasonis antigens attenuates experimental murine colitis through modulation of immunity and microbiota composition. Clin Exp Immunol. 2011;163;250-259.
89. 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.
90. Smith PM, Howitt MR, Panikov N, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 2013;341;569-573.
91. Sokol H, Pigneur B,Watterlot L, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci USA. 2008;105; 16731-16736.
92. Sarosiek J, Peura DA, Guerrant RL, et al. Mucolytic effects of Helicobacter pylori. Scand J Gastroenterol Suppl. 1991;187;47-55.
93. Subramani DB, Johansson ME, Dahlen G, et al. Lactobacillus and Bifidobacterium species do not secrete protease that cleaves the MUC2 mucin which organises the colon mucus. Benef Microbes. 2010;1; 343-350.
94. Li S, Huang XL, Sui JZ, et al. Meta-analysis of randomized controlled trials on the efficacy of probiotics in Helicobacter pylori eradication therapy in children. Eur J Pediatr. 2014;173;153-161.
95. Aiba Y, Suzuki N, Kabir AM, et al. Lactic acid-mediated suppression of Helicobacter pylori by the oral administration of Lactobacillus salivarius as a probiotic in a gnotobiotic murine model. Am J Gastroenterol. 1998;93;2097-2101. (Pubitemid 29076857)
96. Gomi A, Harima-Mizusawa N, Shibahara-Sone H, et al. Effect of Bifidobacterium bifidum BF-1 on gastric protection and mucin production in an acute gastric injury rat model. J Dairy Sci. 2013;96; 832-837.
97. Medellin-Pena MJ, Wang H, Johnson R, et al. Probiotics affect virulence-related gene expression in Escherichia coli O157:H7. Appl Environ Microbiol. 2007;73;4259-4267. (Pubitemid 47068166)
98. Stecher B, Hardt WD. The role of microbiota in infectious disease. Trends Microbiol. 2008;16;107-114.
99. Faridnia F, Hussin AS, Saari N, et al. In vitro binding of mutagenic heterocyclic aromatic amines by Bifidobacterium pseudocatenulatum G4. Benef Microbes. 2010;1;149-154.
100. Mantovani A, Allavena P, Sica A, et al. Cancer-related inflammation. Nature 2008;454;436-444.
101. Kverka M, Tlaskalova-Hogenova H. Two faces of microbiota in inflammatory and autoimmune diseases: triggers and drugs. APMIS. 2013;121; 403-421.
102. Trinchieri G. Cancer and inflammation: an old intuition with rapidly evolving new concepts. Annu Rev Immunol. 2012;30;677-706.
103. Hudcovic T, Stepankova R, Cebra J, et al. The role of microflora in the development of intestinal inflammation: acute and chronic colitis induced by dextran sulfate in germ-free and conventionally reared immunocompetent and immunodeficient mice. Folia Microbiol (Praha). 2001;46;565-572. (Pubitemid 33638684)
104. Blumberg RS, Saubermann LJ, Strober W. Animal models of mucosal inflammation and their relation to human inflammatory bowel disease. Curr Opin Immunol. 1999;11;648-656.
105. Hoffmann M, Messlik A, Kim SC, et al. Impact of a probiotic Enterococcus faecalis in a gnotobiotic mouse model of experimental colitis. Mol Nutr Food Res. 2011;55;703-713.
106. Elson CO. Experimental models of intestinal inflammation? New insights into mechanisms of mucosal homeostasis. In: Ogra P, Mestecky J, Lamm M, et al., eds. Mucosal Immunology. San Diego, CA: Academic Press; 1999:1007-1024.
107. Maslowski KM, Vieira AT, Ng A, et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 2009;461;1282-1286.
108. Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, et al. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 2004;118;229-241. (Pubitemid 38962578)
109. Galon J, Mlecnik B, Bindea G, et al. Towards the introduction of the 'Immunoscore' in the classification of malignant tumours. J Pathol. 2014;232;199-209.
110. Kinnebrew MA, Pamer EG. Innate immune signaling in defense against intestinal microbes. Immunol Rev. 2012;245;113-131.
111. Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 2011;34; 637-650.
112. Tlaskalova-Hogenova H, Cerna J, Mandel L. Peroral immunization of germfree piglets: appearance of antibody-forming cells and antibodies of different isotypes. Scand J Immunol. 1981;13;467-472. (Pubitemid 11143652)
113. Biswas A, Wilmanski J, Forsman H, et al. Negative regulation of Tolllike receptor signaling plays an essential role in homeostasis of the intestine. Eur J Immunol. 2011;41;182-194.
114. Elinav E, Nowarski R, Thaiss CA, et al. Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer 2013;13;759-771.
115. Rider P, Carmi Y, Voronov E, et al. Interleukin-1alpha. Semin Immunol. 2013;25;430-438.
116. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010;140;883-899.
117. Grivennikov SI, Wang K, Mucida D, et al. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 2012;491;254-258.
118. Chin KF, Kallam R, O'Boyle C, et al. Bacterial translocation may influence the long-term survival in colorectal cancer patients. Dis Colon Rectum. 2007;50;323-330. (Pubitemid 46393980)
119. Van der Sluis M, De Koning BA, De Bruijn AC, et al. Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology 2006;131;117-129. (Pubitemid 44015753)
120. Velcich A, YangW, Heyer J, et al. Colorectal cancer in mice genetically deficient in the mucin Muc2. Science 2002;295;1726-1729. (Pubitemid 34202910)
121. Whiteside TL. Regulatory T cell subsets in human cancer: are they regulating for or against tumor progression? Cancer Immunol Immunother. 2014;63;67-72.
122. Viaud S, Saccheri F, Mignot G, et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 2013;342;971-976.
123. Drexler SK, Yazdi AS. Complex roles of inflammasomes in carcinogenesis. Cancer J. 2013;19;468-472.