The Impact of the Gut Microbiome on Colorectal Cancer

Literature Cited

1. Abed J, Emgard JE, Zamir G, Faroja M, Almogy G. et al. 2016. Fap2 mediates Fusobacterium nucleatum colorectal adenocarcinoma enrichment by binding to tumor-expressed Gal-GalNAc. Cell Host Microbe 20:215–25 [Google Scholar]
2. Ahn J, Sinha R, Pei Z, Dominianni C, Wu J. et al. 2013. Human gut microbiome and risk for colorectal cancer. J. Natl. Cancer Inst. 105:1907–11 [Google Scholar]
3. Alam M, Midtvedt T, Uribe A. 1994. Differential cell kinetics in the ileum and colon of germfree rats. Scand. J. Gastroenterol. 29:445–51 [Google Scholar]
4. Allen IC, Wilson JE, Schneider M, Lich JD, Roberts RA. et al. 2012. NLRP12 suppresses colon inflammation and tumorigenesis through the negative regulation of noncanonical NF-κB signaling. Immunity 36:742–54 [Google Scholar]
5. Ambalam P, Raman M, Purama RK, Doble M. 2016. Probiotics, prebiotics and colorectal cancer prevention. Best Pract. Res. Clin. Gastroenterol. 30:119–31 [Google Scholar]
6. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. 2017. Global patterns and trends in colorectal cancer incidence and mortality. Gut 66:683–91 [Google Scholar]
7. Arthur JC, Perez-Chanona E, Muhlbauer M, Tomkovich S, Uronis JM. et al. 2012. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 338:120–23 [Google Scholar]
8. Asfaha S, Hayakawa Y, Muley A, Stokes S, Graham TA. et al. 2015. Krt19⁺/Lgr5⁻ cells are radioresistant cancer-initiating stem cells in the colon and intestine. Cell Stem Cell 16:627–38 [Google Scholar]
9. Barker N. 2014. Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration. Nat. Rev. Mol. Cell Biol. 15:19–33 [Google Scholar]
10. Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H. et al. 2009. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457:608–11 [Google Scholar]
11. Barker N, van Es JH, Kuipers J, Kujala P, van den Born M. et al. 2007. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449:1003–7 [Google Scholar]
12. Becker L, Huang Q, Mashimo H. 2008. Immunostaining of Lgr5, an intestinal stem cell marker, in normal and premalignant human gastrointestinal tissue. Sci. World J. 8:1168–76 [Google Scholar]
13. Belcheva A, Irrazabal T, Robertson SJ, Streutker C, Maughan H. et al. 2014. Gut microbial metabolism drives transformation of MSH2-deficient colon epithelial cells. Cell 158:288–99 [Google Scholar]
14. Bezine E, Malaise Y, Loeuillet A, Chevalier M, Boutet-Robinet E. et al. 2016. Cell resistance to the Cytolethal Distending Toxin involves an association of DNA repair mechanisms. Sci. Rep. 6:36022 [Google Scholar]
15. Biarc J, Nguyen IS, Pini A, Gosse F, Richert S. et al. 2004. Carcinogenic properties of proteins with pro-inflammatory activity from Streptococcus infantarius (formerly S. bovis). Carcinogenesis 25:1477–84 [Google Scholar]
16. Breault DT, Min IM, Carlone DL, Farilla LG, Ambruzs DM. et al. 2008. Generation of mTert-GFP mice as a model to identify and study tissue progenitor cells. PNAS 105:10420–25 [Google Scholar]
17. Buchon N, Broderick NA, Chakrabarti S, Lemaitre B. 2009. Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila. Genes Dev 23:2333–44 [Google Scholar]
18. Buczacki SJ, Zecchini HI, Nicholson AM, Russell R, Vermeulen L. et al. 2013. Intestinal label-retaining cells are secretory precursors expressing Lgr5. Nature 495:65–69 [Google Scholar]
19. Can. Cancer Soc. 2017. Colorectal cancer statistics Canadian Cancer Society Statistics 2017 Toronto, ON: accessed May 17. http://www.cancer.ca/en/cancer-information/cancer-type/colorectal/statistics/?region=on [Google Scholar]
20. Castellarin M, Warren RL, Freeman JD, Dreolini L, Krzywinski M. et al. 2012. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res 22:299–306 [Google Scholar]
21. Chaturvedi R, Asim M, Romero-Gallo J, Barry DP, Hoge S. et al. 2011. Spermine oxidase mediates the gastric cancer risk associated with Helicobacter pylori CagA. Gastroenterology 141:1696–708.e2 [Google Scholar]
22. Chen GY, Shaw MH, Redondo G, Nunez G. 2008. The innate immune receptor Nod1 protects the intestine from inflammation-induced tumorigenesis. Cancer Res 68:10060–67 [Google Scholar]
23. Chen HD, Frankel G. 2005. Enteropathogenic Escherichia coli: unravelling pathogenesis. FEMS Microbiol. Rev. 29:83–98 [Google Scholar]
24. Chen L, Wilson JE, Koenigsknecht MJ, Chou WC, Montgomery SA. et al. 2017. NLRP12 attenuates colon inflammation by maintaining colonic microbial diversity and promoting protective commensal bacterial growth. Nat. Immunol. 18:541–51 [Google Scholar]
25. Chen W, Liu F, Ling Z, Tong X, Xiang C. 2012. Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer. PLOS ONE 7:e39743 [Google Scholar]
26. Cheng H, Leblond CP. 1974.a Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. I. Columnar cell. Am. J. Anat. 141:461–79 [Google Scholar]
27. Cheng H, Leblond CP. 1974.b Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. III. Entero-endocrine cells. Am. J. Anat. 141:503–19 [Google Scholar]
28. Cheng H, Leblond CP. 1974.c Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. V. Unitarian Theory of the origin of the four epithelial cell types. Am. J. Anat. 141:537–61 [Google Scholar]
29. Corredoira JC, Alonso MP, Garcia JF, Casariego E, Coira A. et al. 2005. Clinical characteristics and significance of Streptococcus salivarius bacteremia and Streptococcus bovis bacteremia: a prospective 16-year study. Eur. J. Clin. Microbiol. Infect. Dis. 24:250–55 [Google Scholar]
30. Cougnoux A, Dalmasso G, Martinez R, Buc E, Delmas J. et al. 2014. Bacterial genotoxin colibactin promotes colon tumour growth by inducing a senescence-associated secretory phenotype. Gut 63:1932–42 [Google Scholar]
31. Coussens LM, Werb Z. 2002. Inflammation and cancer. Nature 420:860–67 [Google Scholar]
32. Couturier-Maillard A, Secher T, Rehman A, Normand S, De Arcangelis A. et al. 2013. NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer. J. Clin. Investig. 123:700–11 [Google Scholar]
33. Cronin SJ, Nehme NT, Limmer S, Liegeois S, Pospisilik JA. et al. 2009. Genome-wide RNAi screen identifies genes involved in intestinal pathogenic bacterial infection. Science 325:340–43 [Google Scholar]
34. Dalmasso G, Cougnoux A, Delmas J, Darfeuille-Michaud A, Bonnet R. 2014. The bacterial genotoxin colibactin promotes colon tumor growth by modifying the tumor microenvironment. Gut Microbes 5:675–80 [Google Scholar]
35. Ellmerich S, Scholler M, Duranton B, Gosse F, Galluser M. et al. 2000. Promotion of intestinal carcinogenesis by Streptococcus bovis. Carcinogenesis 21:753–56 [Google Scholar]
36. Epplein M, Pawlita M, Michel A, Peek RM, Cai Q, Blot WJ. 2013. Helicobacter pylori protein-specific antibodies and risk of colorectal cancer. Cancer Epidemiol. Biomark. Prev. 22:1964–74 [Google Scholar]
37. Erdman SE, Rao VP, Poutahidis T, Ihrig MM, Ge Z. et al. 2003. CD4⁺CD25⁺ regulatory lymphocytes require interleukin 10 to interrupt colon carcinogenesis in mice. Cancer Res 63:6042–50 [Google Scholar]
38. Erdman SE, Rao VP, Poutahidis T, Rogers AB, Taylor CL. et al. 2009. Nitric oxide and TNF-α trigger colonic inflammation and carcinogenesis in Helicobacter hepaticus-infected, Rag2-deficient mice. PNAS 106:1027–32 [Google Scholar]
39. Fedor Y, Vignard J, Nicolau-Travers ML, Boutet-Robinet E, Watrin C. et al. 2013. From single-strand breaks to double-strand breaks during S-phase: a new mode of action of the Escherichia coli Cytolethal Distending Toxin. Cell Microbiol 15:1–15 [Google Scholar]
40. Fernandes-Alnemri T, Yu JW, Datta P, Wu J, Alnemri ES. 2009. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458:509–13 [Google Scholar]
41. Franchi L, Amer A, Body-Malapel M, Kanneganti TD, Ozoren N. et al. 2006. Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1β in salmonella-infected macrophages. Nat. Immunol. 7:576–82 [Google Scholar]
42. Fritz JH, Le Bourhis L, Sellge G, Magalhaes JG, Fsihi H. et al. 2007. Nod1-mediated innate immune recognition of peptidoglycan contributes to the onset of adaptive immunity. Immunity 26:445–59 [Google Scholar]
43. Fukata M, Chen A, Vamadevan AS, Cohen J, Breglio K. et al. 2007. Toll-like receptor-4 promotes the development of colitis-associated colorectal tumors. Gastroenterology 133:1869–81 [Google Scholar]
44. Fukata M, Shang L, Santaolalla R, Sotolongo J, Pastorini C. et al. 2011. Constitutive activation of epithelial TLR4 augments inflammatory responses to mucosal injury and drives colitis-associated tumorigenesis. Inflamm. Bowel Dis. 17:1464–73 [Google Scholar]
45. Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G. et al. 2013. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504:446–50 [Google Scholar]
46. Gagniere J, Bonnin V, Jarrousse AS, Cardamone E, Agus A. et al. 2017. Interactions between microsatellite instability and human gut colonization by Escherichia coli in colorectal cancer. Clin. Sci. 131:471–85 [Google Scholar]
47. Gagniere J, Raisch J, Veziant J, Barnich N, Bonnet R. et al. 2016. Gut microbiota imbalance and colorectal cancer. World J. Gastroenterol. 22:501–18 [Google Scholar]
48. Garcia-Gonzalez AP, Ritter AD, Shrestha S, Andersen EC, Yilmaz LS, Walhout AJM. 2017. Bacterial metabolism affects the C. elegans response to cancer chemotherapeutics. Cell 169:431–41.e8 [Google Scholar]
49. Geis AL, Fan H, Wu X, Wu S, Huso DL. et al. 2015. Regulatory T-cell response to enterotoxigenic Bacteroides fragilis colonization triggers IL17-dependent colon carcinogenesis. Cancer Discov 5:1098–109 [Google Scholar]
50. Goodwin AC, Destefano Shields CE, Wu S, Huso DL, Wu X. et al. 2011. Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis. PNAS 108:15354–59 [Google Scholar]
51. Graillot V, Dormoy I, Dupuy J, Shay JW, Huc L. et al. 2016. Genotoxicity of Cytolethal Distending Toxin (CDT) on isogenic human colorectal cell lines: potential promoting effects for colorectal carcinogenesis. Front. Cell Infect. Microbiol. 6:34 [Google Scholar]
52. Greten FR, Eckmann L, Greten TF, Park JM, Li ZW. et al. 2004. IKKβ links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118:285–96 [Google Scholar]
53. Grivennikov SI, Wang K, Mucida D, Stewart CA, Schnabl B. et al. 2012. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 491:254–58 [Google Scholar]
54. Gur C, Ibrahim Y, Isaacson B, Yamin R, Abed J. et al. 2015. Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. Immunity 42:344–55 [Google Scholar]
55. Han Y, Xue X, Jiang M, Guo X, Li P. et al. 2015. LGR5, a relevant marker of cancer stem cells, indicates a poor prognosis in colorectal cancer patients: a meta-analysis. Clin. Res. Hepatol. Gastroenterol. 39:267–73 [Google Scholar]
56. Hooper LV, Gordon JI. 2001. Commensal host-bacterial relationships in the gut. Science 292:1115–18 [Google Scholar]
57. Hornung V, Ablasser A, Charrel-Dennis M, Bauernfeind F, Horvath G. et al. 2009. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458:514–18 [Google Scholar]
58. Hsu HC, Liu YS, Tseng KC, Hsu CL, Liang Y. et al. 2013. Overexpression of Lgr5 correlates with resistance to 5-FU-based chemotherapy in colorectal cancer. Int. J. Colorectal Dis. 28:1535–46 [Google Scholar]
59. Hu B, Elinav E, Huber S, Booth CJ, Strowig T. et al. 2010. Inflammation-induced tumorigenesis in the colon is regulated by caspase-1 and NLRC4. PNAS 107:21635–40 [Google Scholar]
60. Hu B, Elinav E, Huber S, Strowig T, Hao L. et al. 2013. Microbiota-induced activation of epithelial IL-6 signaling links inflammasome-driven inflammation with transmissible cancer. PNAS 110:9862–67 [Google Scholar]
61. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP. et al. 2001. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411:599–603 [Google Scholar]
62. Itzkovitz S, Lyubimova A, Blat IC, Maynard M, van Es J. et al. 2011. Single-molecule transcript counting of stem-cell markers in the mouse intestine. Nat. Cell Biol. 14:106–14 [Google Scholar]
63. Itzkowitz SH, Yio X. 2004. Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation. Am. J. Physiol. Gastrointest. Liver Physiol. 287:G7–17 [Google Scholar]
64. Jadhav U, Saxena M, O'Neill NK, Saadatpour A, Yuan GC. et al. 2017. Dynamic reorganization of chromatin accessibility signatures during dedifferentiation of secretory precursors into Lgr5+ intestinal stem cells. Cell Stem Cell 21:65–77.e5 [Google Scholar]
65. Jiang H, Patel PH, Kohlmaier A, Grenley MO, McEwen DG, Edgar BA. 2009. Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell 137:1343–55 [Google Scholar]
66. Jones RM, Luo L, Ardita CS, Richardson AN, Kwon YM. et al. 2013. Symbiotic lactobacilli stimulate gut epithelial proliferation via Nox-mediated generation of reactive oxygen species. EMBO J 32:3017–28 [Google Scholar]
67. Kaiko GE, Ryu SH, Koues OI, Collins PL, Solnica-Krezel L. et al. 2016. The colonic crypt protects stem cells from microbiota-derived metabolites. Cell 167:1708–20 [Google Scholar]
68. Kanno T, Matsuki T, Oka M, Utsunomiya H, Inada K. et al. 2009. Gastric acid reduction leads to an alteration in lower intestinal microflora. Biochem. Biophys. Res. Commun. 381:666–70 [Google Scholar]
69. Karki R, Man SM, Malireddi RK, Kesavardhana S, Zhu Q. et al. 2016. NLRC3 is an inhibitory sensor of PI3K–mTOR pathways in cancer. Nature 540:583–87 [Google Scholar]
70. Khor B, Gardet A, Xavier RJ. 2011. Genetics and pathogenesis of inflammatory bowel disease. Nature 474:307–17 [Google Scholar]
71. Koblansky AA, Truax AD, Liu R, Montgomery SA, Ding S. et al. 2016. The innate immune receptor NLRX1 functions as a tumor suppressor by reducing colon tumorigenesis and key tumor-promoting signals. Cell Rep 14:2562–75 [Google Scholar]
72. Kostic AD, Chun E, Robertson L, Glickman JN, Gallini CA. et al. 2013. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 14:207–15 [Google Scholar]
73. Kostic AD, Gevers D, Pedamallu CS, Michaud M, Duke F. et al. 2012. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res 22:292–98 [Google Scholar]
74. Kreso A, Dick JE. 2014. Evolution of the cancer stem cell model. Cell Stem Cell 14:275–91 [Google Scholar]
75. Kreso A, van Galen P, Pedley NM, Lima-Fernandes E, Frelin C. et al. 2014. Self-renewal as a therapeutic target in human colorectal cancer. Nat. Med. 20:29–36 [Google Scholar]
76. Kryczek I, Lin Y, Nagarsheth N, Peng D, Zhao L. et al. 2014. IL-22⁺CD4⁺ T cells promote colorectal cancer stemness via STAT3 transcription factor activation and induction of the methyltransferase DOT1L. Immunity 40:772–84 [Google Scholar]
77. Li L, Clevers H. 2010. Coexistence of quiescent and active adult stem cells in mammals. Science 327:542–45 [Google Scholar]
78. Li N, Yousefi M, Nakauka-Ddamba A, Jain R, Tobias J. et al. 2014. Single-cell analysis of proxy reporter allele-marked epithelial cells establishes intestinal stem cell hierarchy. Stem Cell Rep 3:876–91 [Google Scholar]
79. Liu R, Truax AD, Chen L, Hu P, Li Z. et al. 2015. Expression profile of innate immune receptors, NLRs and AIM2, in human colorectal cancer: correlation with cancer stages and inflammasome components. Oncotarget 6:33456–69 [Google Scholar]
80. Liu Z, Dai W, Jiang L, Cheng Y. 2014. Over-expression of LGR5 correlates with poor survival of colon cancer in mice as well as in patients. Neoplasma 61:177–85 [Google Scholar]
81. Lloyd-Price J, Abu-Ali G, Huttenhower C. 2016. The healthy human microbiome. Genome Med 8:51 [Google Scholar]
82. Lowe EL, Crother TR, Rabizadeh S, Hu B, Wang H. et al. 2010. Toll-like receptor 2 signaling protects mice from tumor development in a mouse model of colitis-induced cancer. PLOS ONE 5:e13027 [Google Scholar]
83. Man SM, Zhu Q, Zhu L, Liu Z, Karki R. et al. 2015. Critical role for the DNA sensor AIM2 in stem cell proliferation and cancer. Cell 162:45–58 [Google Scholar]
84. Mariathasan S, Newton K, Monack DM, Vucic D, French DM. et al. 2004. Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature 430:213–18 [Google Scholar]
85. McCaskey SJ, Rondini EA, Clinthorne JF, Langohr IM, Gardner EM, Fenton JI. 2012. Increased presence of effector lymphocytes during Helicobacter hepaticus-induced colitis. World J. Gastroenterol. 18:1459–69 [Google Scholar]
86. Micchelli CA, Perrimon N. 2006. Evidence that stem cells reside in the adult Drosophila midgut epithelium. Nature 439:475–79 [Google Scholar]
87. Mima K, Nishihara R, Qian ZR, Cao Y, Sukawa Y. et al. 2016. Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis. Gut 65:1973–80 [Google Scholar]
88. Mima K, Sukawa Y, Nishihara R, Qian ZR, Yamauchi M. et al. 2015. Fusobacterium nucleatum and T cells in colorectal carcinoma. JAMA Oncol 1:653–61 [Google Scholar]
89. Mira-Pascual L, Cabrera-Rubio R, Ocon S, Costales P, Parra A. et al. 2015. Microbial mucosal colonic shifts associated with the development of colorectal cancer reveal the presence of different bacterial and archaeal biomarkers. J. Gastroenterol. 50:167–79 [Google Scholar]
90. Moayyedi P. 2016. Fecal transplantation: any real hope for inflammatory bowel disease. Curr. Opin. Gastroenterol. 32:282–86 [Google Scholar]
91. Monira S, Nakamura S, Gotoh K, Izutsu K, Watanabe H. et al. 2013. Metagenomic profile of gut microbiota in children during cholera and recovery. Gut Pathog 5:1 [Google Scholar]
92. Montgomery RK, Carlone DL, Richmond CA, Farilla L, Kranendonk ME. et al. 2011. Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells. PNAS 108:179–84 [Google Scholar]
93. Munoz J, Stange DE, Schepers AG, van de Wetering M, Koo BK. et al. 2012. The Lgr5 intestinal stem cell signature: robust expression of proposed quiescent ‘+4’ cell markers. EMBO J 31:3079–91 [Google Scholar]
94. Myant KB, Cammareri P, McGhee EJ, Ridgway RA, Huels DJ. et al. 2013. ROS production and NF-κB activation triggered by RAC1 facilitate WNT-driven intestinal stem cell proliferation and colorectal cancer initiation. Cell Stem Cell 12:761–73 [Google Scholar]
95. Nagamine CM, Rogers AB, Fox JG, Schauer DB. 2008.a Helicobacter hepaticus promotes azoxymethane-initiated colon tumorigenesis in BALB/c-IL10-deficient mice. Int. J. Cancer 122:832–38 [Google Scholar]
96. Nagamine CM, Sohn JJ, Rickman BH, Rogers AB, Fox JG, Schauer DB. 2008.b Helicobacter hepaticus infection promotes colon tumorigenesis in the BALB/c-Rag2^−/−Apc^Min/+ mouse. Infect. Immun. 76:2758–66 [Google Scholar]
97. Neal MD, Sodhi CP, Jia H, Dyer M, Egan CE. et al. 2012. Toll-like receptor 4 is expressed on intestinal stem cells and regulates their proliferation and apoptosis via the p53 up-regulated modulator of apoptosis. J. Biol. Chem. 287:37296–308 [Google Scholar]
98. Nicolson MC, Fennell DA, Ferry D, O'Byrne K, Shah R. et al. 2013. Thymidylate synthase expression and outcome of patients receiving pemetrexed for advanced nonsquamous non–small-cell lung cancer in a prospective blinded assessment phase II clinical trial. J. Thorac. Oncol. 8:930–39 [Google Scholar]
99. Nigro G, Rossi R, Commere PH, Jay P, Sansonetti PJ. 2014. The cytosolic bacterial peptidoglycan sensor Nod2 affords stem cell protection and links microbes to gut epithelial regeneration. Cell Host Microbe 15:792–98 [Google Scholar]
100. Nosho K, Sukawa Y, Adachi Y, Ito M, Mitsuhashi K. et al. 2016. Association of Fusobacterium nucleatum with immunity and molecular alterations in colorectal cancer. World J. Gastroenterol. 22:557–66 [Google Scholar]
101. Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF. et al. 2001. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411:603–6 [Google Scholar]
102. Olier M, Marcq I, Salvador-Cartier C, Secher T, Dobrindt U. et al. 2012. Genotoxicity of Escherichia coli Nissle 1917 strain cannot be dissociated from its probiotic activity. Gut Microbes 3:501–9 [Google Scholar]
103. Pandey S, Singh S, Anang V, Bhatt AN, Natarajan K, Dwarakanath BS. 2015. Pattern recognition receptors in cancer progression and metastasis. Cancer Growth Metastasis 8:25–34 [Google Scholar]
104. Papastergiou V, Karatapanis S, Georgopoulos SD. 2016. Helicobacter pylori and colorectal neoplasia: Is there a causal link. World J. Gastroenterol. 22:649–58 [Google Scholar]
105. Pedron T, Mulet C, Dauga C, Frangeul L, Chervaux C. et al. 2012. A crypt-specific core microbiota resides in the mouse colon. mBio 3:e00116–12 [Google Scholar]
106. Poretsky R, Rodriguez RL, Luo C, Tsementzi D, Konstantinidis KT. 2014. Strengths and limitations of 16S rRNA gene amplicon sequencing in revealing temporal microbial community dynamics. PLOS ONE 9:e93827 [Google Scholar]
107. Potten CS. 1977. Extreme sensitivity of some intestinal crypt cells to X and gamma irradiation. Nature 269:518–21 [Google Scholar]
108. Powell AE, Wang Y, Li Y, Poulin EJ, Means AL. et al. 2012. The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor. Cell 149:146–58 [Google Scholar]
109. Purcell RV, Pearson J, Aitchison A, Dixon L, Frizelle FA, Keenan JI. 2017. Colonization with enterotoxigenic Bacteroides fragilis is associated with early-stage colorectal neoplasia. PLOS ONE 12:e0171602 [Google Scholar]
110. Rakoff-Nahoum S, Medzhitov R. 2007. Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88. Science 317:124–27 [Google Scholar]
111. Rathinam VA, Jiang Z, Waggoner SN, Sharma S, Cole LE. et al. 2010. The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat. Immunol. 11:395–402 [Google Scholar]
112. Reikvam DH, Erofeev A, Sandvik A, Grcic V, Jahnsen FL. et al. 2011. Depletion of murine intestinal microbiota: effects on gut mucosa and epithelial gene expression. PLOS ONE 6:e17996 [Google Scholar]
113. Renga M, Brandi G, Paganelli GM, Calabrese C, Papa S. et al. 1997. Rectal cell proliferation and colon cancer risk in patients with hypergastrinaemia. Gut 41:330–32 [Google Scholar]
114. Robertson SJ, Zhou JY, Geddes K, Rubino SJ, Cho JH. et al. 2013. Nod1 and Nod2 signaling does not alter the composition of intestinal bacterial communities at homeostasis. Gut Microbes 4:222–31 [Google Scholar]
115. Rubinstein MR, Wang X, Liu W, Hao Y, Cai G, Han YW. 2013. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin. Cell Host Microbe 14:195–206 [Google Scholar]
116. Ruoff KL, Miller SI, Garner CV, Ferraro MJ, Calderwood SB. 1989. Bacteremia with Streptococcus bovis and Streptococcus salivarius: clinical correlates of more accurate identification of isolates. J. Clin. Microbiol. 27:305–8 [Google Scholar]
117. Salcedo R, Worschech A, Cardone M, Jones Y, Gyulai Z. et al. 2010. MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18. J. Exp. Med. 207:1625–36 [Google Scholar]
118. Sangiorgi E, Capecchi MR. 2008. Bmi1 is expressed in vivo in intestinal stem cells. Nat. Genet. 40:915–20 [Google Scholar]
119. Santaolalla R, Sussman DA, Ruiz JR, Davies JM, Pastorini C. et al. 2013. TLR4 activates the β-catenin pathway to cause intestinal neoplasia. PLOS ONE 8:e63298 [Google Scholar]
120. Sasaki N, Sachs N, Wiebrands K, Ellenbroek SI, Fumagalli A. et al. 2016. Reg4⁺ deep crypt secretory cells function as epithelial niche for Lgr5⁺ stem cells in colon. PNAS 113:E5399–407 [Google Scholar]
121. Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N. et al. 2009. Single Lgr5 stem cells build crypt–villus structures in vitro without a mesenchymal niche. Nature 459:262–65 [Google Scholar]
122. Scanlan PD. 2017. Bacteria-bacteriophage coevolution in the human gut: implications for microbial diversity and functionality. Trends Microbiol 25:614–23 [Google Scholar]
123. Schepers AG, Snippert HJ, Stange DE, van den Born M, van Es JH. et al. 2012. Lineage tracing reveals Lgr5⁺ stem cell activity in mouse intestinal adenomas. Science 337:730–35 [Google Scholar]
124. Schwabe RF, Jobin C. 2013. The microbiome and cancer. Nat. Rev. Cancer 13:800–12 [Google Scholar]
125. Schwitalla S, Fingerle AA, Cammareri P, Nebelsiek T, Goktuna SI. et al. 2013. Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties. Cell 152:25–38 [Google Scholar]
126. Scott TA, Quintaneiro LM, Norvaisas P, Lui PP, Wilson MP. et al. 2017. Host-microbe co-metabolism dictates cancer drug efficacy in C. elegans. Cell 169:442–56 [Google Scholar]
127. Sears CL, Geis AL, Housseau F. 2014. Bacteroides fragilis subverts mucosal biology: from symbiont to colon carcinogenesis. J. Clin. Investig. 124:4166–72 [Google Scholar]
128. Seregin SS, Golovchenko N, Schaf B, Chen J, Eaton KA, Chen GY. 2017. NLRP6 function in inflammatory monocytes reduces susceptibility to chemically induced intestinal injury. Mucosal Immunol 10:434–45 [Google Scholar]
129. Shazali N, Foo HL, Loh TC, Choe DW, Abdul Rahim R. 2014. Prevalence of antibiotic resistance in lactic acid bacteria isolated from the faeces of broiler chicken in Malaysia. Gut Pathog 6:1 [Google Scholar]
130. Shmuely H, Passaro D, Figer A, Niv Y, Pitlik S. et al. 2001. Relationship between Helicobacter pylori CagA status and colorectal cancer. Am. J. Gastroenterol. 96:3406–10 [Google Scholar]
131. Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K. et al. 2015. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy. Science 350:1084–89 [Google Scholar]
132. Soares F, Tattoli I, Rahman MA, Robertson SJ, Belcheva A. et al. 2014. The mitochondrial protein NLRX1 controls the balance between extrinsic and intrinsic apoptosis. J. Biol. Chem. 289:19317–30 [Google Scholar]
133. Sobhani I, Tap J, Roudot-Thoraval F, Roperch JP, Letulle S. et al. 2011. Microbial dysbiosis in colorectal cancer (CRC) patients. PLOS ONE 6:e16393 [Google Scholar]
134. Stevens CE, Leblond CP. 1947. Rate of renewal of the cells of the intestinal epithelium in the rat. Anat. Rec. 97:373 [Google Scholar]
135. Stewart BW, Wild C. 2014. World Cancer Report 2014 Lyon, Fr.: Int. Agency Res. Cancer http://www.who.int/cancer/publications/WRC_2014/en/ [Google Scholar]
136. Strauss J, Kaplan GG, Beck PL, Rioux K, Panaccione R. et al. 2011. Invasive potential of gut mucosa-derived Fusobacterium nucleatum positively correlates with IBD status of the host. Inflamm. Bowel Dis. 17:1971–78 [Google Scholar]
137. Swidsinski A, Loening-Baucke V, Lochs H, Hale LP. 2005. Spatial organization of bacterial flora in normal and inflamed intestine: a fluorescence in situ hybridization study in mice. World J. Gastroenterol. 11:1131–40 [Google Scholar]
138. Takahashi H, Ishii H, Nishida N, Takemasa I, Mizushima T. et al. 2011. Significance of Lgr5^+ve cancer stem cells in the colon and rectum. Ann. Surg. Oncol. 18:1166–74 [Google Scholar]
139. Takeda N, Jain R, LeBoeuf MR, Wang Q, Lu MM, Epstein JA. 2011. Interconversion between intestinal stem cell populations in distinct niches. Science 334:1420–24 [Google Scholar]
140. Tattoli I, Killackey SA, Foerster EG, Molinaro R, Maisonneuve C. et al. 2016. NLRX1 acts as an epithelial-intrinsic tumor suppressor through the modulation of TNF-mediated proliferation. Cell Rep 14:2576–86 [Google Scholar]
141. Tetteh PW, Farin HF, Clevers H. 2015. Plasticity within stem cell hierarchies in mammalian epithelia. Trends Cell Biol 25:100–8 [Google Scholar]
142. Tian H, Biehs B, Warming S, Leong KG, Rangell L. et al. 2011. A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature 478:255–59 [Google Scholar]
143. Tjalsma H, Boleij A, Marchesi JR, Dutilh BE. 2012. A bacterial driver–passenger model for colorectal cancer: beyond the usual suspects. Nat. Rev. Microbiol. 10:575–82 [Google Scholar]
144. Todaro M, Gaggianesi M, Catalano V, Benfante A, Iovino F. et al. 2014. CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis. Cell Stem Cell 14:342–56 [Google Scholar]
145. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. 2015. Global cancer statistics, 2012.. CA Cancer J. Clin. 65:87–108 [Google Scholar]
146. Tringe SG, Hugenholtz P. 2008. A renaissance for the pioneering 16S rRNA gene. Curr. Opin. Microbiol. 11:442–46 [Google Scholar]
147. Tsugawa H, Suzuki H, Saya H, Hatakeyama M, Hirayama T. et al. 2012. Reactive oxygen species-induced autophagic degradation of Helicobacter pylori CagA is specifically suppressed in cancer stem-like cells. Cell Host Microbe 12:764–77 [Google Scholar]
148. Udden SMN, Peng L, Gan JL, Shelton JM, Malter JS. et al. 2017. NOD2 suppresses colorectal tumorigenesis via downregulation of the TLR pathways. Cell Rep 19:2756–70 [Google Scholar]
149. Vermeulen L, De Sousa EMF, van der Heijden M, Cameron K, de Jong JH. et al. 2010. Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat. Cell Biol. 12:468–76 [Google Scholar]
150. Vermeulen L, Snippert HJ. 2014. Stem cell dynamics in homeostasis and cancer of the intestine. Nat. Rev. Cancer 14:468–80 [Google Scholar]
151. Vétizou M, Pitt JM, Daillère R, Lepage P, Waldschmitt N. et al. 2015. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350:1079–84 [Google Scholar]
152. Viaud S, Daillère R, Boneca IG, Lepage P, Langella P. et al. 2015. Gut microbiome and anticancer immune response: really hot sh*t!. Cell Death Differ 22:199–214 [Google Scholar]
153. Visvader JE. 2011. Cells of origin in cancer. Nature 469:314–22 [Google Scholar]
154. Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC. et al. 1988. Genetic alterations during colorectal-tumor development. N. Engl. J. Med. 319:525–32 [Google Scholar]
155. Wang C, Gong G, Sheh A, Muthupalani S, Bryant EM. et al. 2017. Interleukin-22 drives nitric oxide-dependent DNA damage and dysplasia in a murine model of colitis-associated cancer. Mucosal Immunol 10:61504–17 [Google Scholar]
156. Wang HF, Li LF, Guo SH, Zeng QY, Ning F. et al. 2016. Evaluation of antibody level against Fusobacterium nucleatum in the serological diagnosis of colorectal cancer. Sci. Rep. 6:33440 [Google Scholar]
157. Wang T, Cai G, Qiu Y, Fei N, Zhang M. et al. 2012. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J 6:320–29 [Google Scholar]
158. Watanabe T, Asano N, Murray PJ, Ozato K, Tailor P. et al. 2008. Muramyl dipeptide activation of nucleotide-binding oligomerization domain 2 protects mice from experimental colitis. J. Clin. Investig. 118:545–59 [Google Scholar]
159. Weir TL, Manter DK, Sheflin AM, Barnett BA, Heuberger AL, Ryan EP. 2013. Stool microbiome and metabolome differences between colorectal cancer patients and healthy adults. PLOS ONE 8:e70803 [Google Scholar]
160. Westphalen CB, Asfaha S, Hayakawa Y, Takemoto Y, Lukin DJ. et al. 2014. Long-lived intestinal tuft cells serve as colon cancer-initiating cells. J. Clin. Investig. 124:1283–95 [Google Scholar]
161. Wilson JE, Petrucelli AS, Chen L, Koblansky AA, Truax AD. et al. 2015. Inflammasome-independent role of AIM2 in suppressing colon tumorigenesis via DNA-PK and Akt. Nat. Med. 21:906–13 [Google Scholar]
162. Wirtz S, Neufert C, Weigmann B, Neurath MF. 2007. Chemically induced mouse models of intestinal inflammation. Nat. Protoc. 2:541–46 [Google Scholar]
163. Wu S, Morin PJ, Maouyo D, Sears CL. 2003. Bacteroides fragilis enterotoxin induces c-Myc expression and cellular proliferation. Gastroenterology 124:392–400 [Google Scholar]
164. Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X. et al. 2009. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat. Med. 15:1016–22 [Google Scholar]
165. Yan KS, Chia LA, Li X, Ootani A, Su J. et al. 2012. The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations. PNAS 109:466–71 [Google Scholar]
166. Yan KS, Gevaert O, Zheng GXY, Anchang B, Probert CS. et al. 2017. Intestinal enteroendocrine lineage cells possess homeostatic and injury-inducible stem cell activity. Cell Stem Cell 21:78–90.e6 [Google Scholar]
167. Yanai H, Atsumi N, Tanaka T, Nakamura N, Komai Y. et al. 2017. Intestinal cancer stem cells marked by Bmi1 or Lgr5 expression contribute to tumor propagation via clonal expansion. Sci. Rep. 7:41838 [Google Scholar]
168. Yang Y, Weng W, Peng J, Hong L, Yang L. et al. 2017. Fusobacterium nucleatum increases proliferation of colorectal cancer cells and tumor development in mice by activating Toll-like receptor 4 signaling to nuclear factor-κB, and up-regulating expression of microRNA-21. Gastroenterology 152:851–66.e24 [Google Scholar]
169. Zackular JP, Baxter NT, Iverson KD, Sadler WD, Petrosino JF. et al. 2013. The gut microbiome modulates colon tumorigenesis. mBio 4:e00692–13 [Google Scholar]
170. Zaki MH, Vogel P, Body-Malapel M, Lamkanfi M, Kanneganti TD. 2010. IL-18 production downstream of the Nlrp3 inflammasome confers protection against colorectal tumor formation. J. Immunol. 185:4912–20 [Google Scholar]
171. Zaki MH, Vogel P, Malireddi RK, Body-Malapel M, Anand PK. et al. 2011. The NOD-like receptor NLRP12 attenuates colon inflammation and tumorigenesis. Cancer Cell 20:649–60 [Google Scholar]
172. Zanello G, Goethel A, Rouquier S, Prescott D, Robertson SJ. et al. 2016. The cytosolic microbial receptor Nod2 regulates small intestinal crypt damage and epithelial regeneration following T cell–induced enteropathy. J. Immunol. 197:345–55 [Google Scholar]
173. Zhan Y, Seregin SS, Chen J, Chen GY. 2016. Nod1 limits colitis-associated tumorigenesis by regulating IFN-γ production. J. Immunol. 196:5121–29 [Google Scholar]