The gastrointestinal microbiota and its role in oncogenesis

Best Practice and Research: Clinical Gastroenterology

Volumn 31, Issue 6, 2017, Pages 607-618

  Lam, S Y ^a   Yu, J ^b,c   Wong, S H ^b,c   Peppelenbosch, M P ^a   Fuhler, G M ^a  

^a ERASMUS MEDICAL CENTER   (Netherlands)

^b CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

^c CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

Author keywords

Cancer; Colorectal; Gastric; Gastrointestinal; Microbiome; Microbiota; Oesophageal; Oral

Indexed keywords

ANAL CANAL; BACTERIAL MICROBIOME; CARCINOGENESIS; COLORECTAL CANCER; DYSBIOSIS; HUMAN; INTESTINE FLORA; LARGE INTESTINE; MICROBIAL COMMUNITY; MOUTH CAVITY; REVIEW; STOMACH; STOMACH CANCER; TUMOR GROWTH; UPPER GASTROINTESTINAL TRACT; CELL TRANSFORMATION; GASTROINTESTINAL TUMOR; GENETICS; MICROBIOLOGY; PATHOLOGY;

CARCINOGENESIS; CELL TRANSFORMATION, NEOPLASTIC; GASTROINTESTINAL MICROBIOME; GASTROINTESTINAL NEOPLASMS; HUMANS;

EID: 85028810546     PISSN: 15216918     EISSN: 15321916     Source Type: Journal    
DOI: 10.1016/j.bpg.2017.09.010     Document Type: Review

References (162)

1. Lynch, S.V., Pedersen, O., et al. The human intestinal microbiome in health and disease. N Engl J Med 375:24 (2016), 2369–2379.
2. Tjalsma, H., Boleij, A., Marchesi, J.R., Dutilh, B.E., et al. A bacterial driver-passenger model for colorectal cancer: beyond the usual suspects. Nat Rev Microbiol 10:8 (2012), 575–582.
3. Sender, R., Fuchs, S., Milo, R., et al. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol, 14(8), 2016, e1002533.
4. Sender, R., Fuchs, S., Milo, R., et al. Are we really vastly Outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell 164:3 (2016), 337–340.
5. Cho, I., Blaser, M.J., et al. The human microbiome: at the interface of health and disease. Nat Rev Genet 13:4 (2012), 260–270.
6. Sheflin, A.M., Whitney, A.K., Weir, T.L., et al. Cancer-promoting effects of microbial dysbiosis. Curr Oncol Rep, 16(10), 2014, 406.
7. Vogtmann, E., Goedert, J.J., et al. Epidemiologic studies of the human microbiome and cancer. Br J Cancer 114:3 (2016), 237–242.
8. Costello, E.K., Lauber, C.L., Hamady, M., Fierer, N., Gordon, J.I., Knight, R., et al. Bacterial community variation in human body habitats across space and time. Science 326:5960 (2009), 1694–1697.
9. Plummer, M., de Martel, C., Vignat, J., Ferlay, J., Bray, F., Franceschi, S., et al. Global burden of cancers attributable to infections in 2012: a synthetic analysis. Lancet Glob Health 4:9 (2016), e609–e616.
10. WHO, International Agency for Research of Cancer (IARC), et al. Schistosomes, liver flukes and Helicobacter pylori. IARC working group on the evaluation of carcinogenic risks to humans. Lyon, 7-14 June 1994. IARC Monogr Eval Carcinog Risks Hum 61 (1994), 177–240.
11. Warnakulasuriya, S., et al. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 45:4–5 (2009), 309–316.
12. Chen, Y.K., Huang, H.C., Lin, L.M., Lin, C.C., et al. Primary oral squamous cell carcinoma: an analysis of 703 cases in southern Taiwan. Oral Oncol 35:2 (1999), 173–179.
13. Chocolatewala, N., Chaturvedi, P., Desale, R., et al. The role of bacteria in oral cancer. Indian J Med Paediatr Oncol 31:4 (2010), 126–131.
14. Perera, M., Al-Hebshi, N.N., Speicher, D.J., Perera, I., Johnson, N.W., et al. Emerging role of bacteria in oral carcinogenesis: a review with special reference to perio-pathogenic bacteria. J Oral Microbiol, 8, 2016, 32762.
15. Hooper, S.J., Crean, S.J., Fardy, M.J., Lewis, M.A., Spratt, D.A., Wade, W.G., et al. A molecular analysis of the bacteria present within oral squamous cell carcinoma. J Med Microbiol 56:Pt 12 (2007), 1651–1659.
16. Hooper, S.J., Crean, S.J., Lewis, M.A., Spratt, D.A., Wade, W.G., Wilson, M.J., et al. Viable bacteria present within oral squamous cell carcinoma tissue. J Clin Microbiol 44:5 (2006), 1719–1725.
17. Pushalkar, S., Ji, X., Li, Y., Estilo, C., Yegnanarayana, R., Singh, B., et al. Comparison of oral microbiota in tumor and non-tumor tissues of patients with oral squamous cell carcinoma. BMC Microbiol, 12, 2012, 144.
18. Al-Hebshi, N.N., Nasher, A.T., Idris, A.M., Chen, T., et al. Robust species taxonomy assignment algorithm for 16S rRNA NGS reads: application to oral carcinoma samples. J Oral Microbiol, 7, 2015, 28934.
19. Mager, D.L., Haffajee, A.D., Devlin, P.M., Norris, C.M., Posner, M.R., Goodson, J.M., et al. The salivary microbiota as a diagnostic indicator of oral cancer: a descriptive, non-randomized study of cancer-free and oral squamous cell carcinoma subjects. J Transl Med, 3, 2005, 27.
20. Pushalkar, S., Mane, S.P., Ji, X., Li, Y., Evans, C., Crasta, O.R., et al. Microbial diversity in saliva of oral squamous cell carcinoma. FEMS Immunol Med Microbiol 61:3 (2011), 269–277.
21. Hu, X., Zhang, Q., Hua, H., Chen, F., et al. Changes in the salivary microbiota of oral leukoplakia and oral cancer. Oral Oncol 56 (2016), e6–8.
22. Schmidt, B.L., Kuczynski, J., Bhattacharya, A., Huey, B., Corby, P.M., Queiroz, E.L., et al. Changes in abundance of oral microbiota associated with oral cancer. PLoS One, 9(6), 2014, e98741.
23. Mok, S.F., Karuthan, C., Cheah, Y.K., Ngeow, W.C., Rosnah, Z., Yap, S.F., et al. The oral microbiome community variations associated with normal, potentially malignant disorders and malignant lesions of the oral cavity. Malays J Pathol 39:1 (2017), 1–15.
24. D'Souza, G., Kreimer, A.R., Viscidi, R., Pawlita, M., Fakhry, C., Koch, W.M., et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 356:19 (2007), 1944–1956.
25. Walvik, L., Svensson, A.B., Friborg, J., Lajer, C.B., et al. The association between human papillomavirus and oropharyngeal squamous cell Carcinoma: reviewed according to the Bradford Hill criteria for causality. Oral Oncol 63 (2016), 61–65.
26. Lukes, P., Pavlik, E., Potuznikova, B., Nartova, E., Foltynova, E., Plzak, J., et al. Detection of Helicobacter pylori in oropharyngeal lymphatic tissue with real-time PCR and assessment of its carcinogenic potential. Eur Arch Otorhinolaryngol 271:2 (2014), 399–405.
27. van Baal, J.W., Diks, S.H., Wanders, R.J., Rygiel, A.M., Milano, F., Joore, J., et al. Comparison of kinome profiles of Barrett's esophagus with normal squamous esophagus and normal gastric cardia. Cancer Res 66:24 (2006), 11605–11612.
28. Ding, G.C., Ren, J.L., Chang, F.B., Li, J.L., Yuan, L., Song, X., et al. Human papillomavirus DNA and P16(INK4A) expression in concurrent esophageal and gastric cardia cancers. World J Gastroenterol 16:46 (2010), 5901–5906.
29. Rajendra, S., Wang, B., Snow, E.T., Sharma, P., Pavey, D., Merrett, N., et al. Transcriptionally active human papillomavirus is strongly associated with Barrett's dysplasia and esophageal adenocarcinoma. Am J Gastroenterol 108:7 (2013), 1082–1093.
30. Yang, L., Chaudhary, N., Baghdadi, J., Pei, Z., et al. Microbiome in reflux disorders and esophageal adenocarcinoma. Cancer J 20:3 (2014), 207–210.
31. Pei, Z., Bini, E.J., Yang, L., Zhou, M., Francois, F., Blaser, M.J., et al. Bacterial biota in the human distal esophagus. Proc Natl Acad Sci U. S. A 101:12 (2004), 4250–4255.
32. Yang, L., Lu, X., Nossa, C.W., Francois, F., Peek, R.M., Pei, Z., et al. Inflammation and intestinal metaplasia of the distal esophagus are associated with alterations in the microbiome. Gastroenterology 137:2 (2009), 588–597.
33. Rustgi, A.K., El-Serag, H.B., et al. Esophageal carcinoma. N Engl J Med 371:26 (2014), 2499–2509.
34. Baghdadi, J., Chaudhary, N., Pei, Z., Yang, L., et al. Microbiome, innate immunity, and esophageal adenocarcinoma. Clin Lab Med 34:4 (2014), 721–732.
35. Blackett, K.L., Siddhi, S.S., Cleary, S., Steed, H., Miller, M.H., Macfarlane, S., et al. Oesophageal bacterial biofilm changes in gastro-oesophageal reflux disease, Barrett's and oesophageal carcinoma: association or causality?. Aliment Pharmacol Ther 37:11 (2013), 1084–1092.
36. Gall, A., Fero, J., McCoy, C., Claywell, B.C., Sanchez, C.A., Blount, P.L., et al. Bacterial composition of the human upper gastrointestinal tract microbiome is dynamic and associated with genomic instability in a Barrett's esophagus cohort. PLoS One, 10(6), 2015, e0129055.
37. Gashi, Z., Sherifi, F., Shabani, R., et al. The prevalence of helicobacter pylori infection in patients with reflux esophagitis - our experience. Med Arch 67:6 (2013), 402–404.
38. Anderson, L.A., Murphy, S.J., Johnston, B.T., Watson, R.G., Ferguson, H.R., Bamford, K.B., et al. Relationship between Helicobacter pylori infection and gastric atrophy and the stages of the oesophageal inflammation, metaplasia, adenocarcinoma sequence: results from the FINBAR case-control study. Gut 57:6 (2008), 734–739.
39. Xie, F.J., Zhang, Y.P., Zheng, Q.Q., Jin, H.C., Wang, F.L., Chen, M., et al. Helicobacter pylori infection and esophageal cancer risk: an updated meta-analysis. World J Gastroenterol 19:36 (2013), 6098–6107.
40. Fischbach, L.A., Graham, D.Y., Kramer, J.R., Rugge, M., Verstovsek, G., Parente, P., et al. Association between Helicobacter pylori and Barrett's esophagus: a case-control study. Am J Gastroenterol 109:3 (2014), 357–368.
41. Rubenstein, J.H., Inadomi, J.M., Scheiman, J., Schoenfeld, P., Appelman, H., Zhang, M., et al. Association between Helicobacter pylori and Barrett's esophagus, erosive esophagitis, and gastroesophageal reflux symptoms. Clin Gastroenterol Hepatol 12:2 (2014), 239–245.
42. Yaghoobi, M., Farrokhyar, F., Yuan, Y., Hunt, R.H., et al. Is there an increased risk of GERD after Helicobacter pylori eradication?: a meta-analysis. Am J Gastroenterol 105:5 (2010), 1007–1013 quiz 6, 14.
43. Shahabi, S., Rasmi, Y., Jazani, N.H., Hassan, Z.M., et al. Protective effects of Helicobacter pylori against gastroesophageal reflux disease may be due to a neuroimmunological anti-inflammatory mechanism. Immunol Cell Biol 86:2 (2008), 175–178.
44. Warren, J., et al. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1:8336 (1983), 1273–1275.
45. Sanduleanu, S., Jonkers, D., De Bruine, A., Hameeteman, W., Stockbrügger, R.W., et al. Non-Helicobacter pylori bacterial flora during acid-suppressive therapy: differential findings in gastric juice and gastric mucosa. Aliment Pharmacol Ther 15:3 (2001), 379–388.
46. Vartoukian, S.R., Palmer, R.M., Wade, W.G., et al. Strategies for culture of ‘unculturable’ bacteria. FEMS Microbiol Lett 309:1 (2010), 1–7.
47. Delgado, S., Cabrera-Rubio, R., Mira, A., Suarez, A., Mayo, B., et al. Microbiological survey of the human gastric ecosystem using culturing and pyrosequencing methods. Microb Ecol 65:3 (2013), 763–772.
48. Wang, Z.K., Yang, Y.S., et al. Upper gastrointestinal microbiota and digestive diseases. World J Gastroenterol 19:10 (2013), 1541–1550.
49. Engstrand, L., Lindberg, M., et al. Helicobacter pylori and the gastric microbiota. Best Pract Res Clin Gastroenterol 27:1 (2013), 39–45.
50. Ianiro, G., Molina-Infante, J., Gasbarrini, A., et al. Gastric microbiota. Helicobacter 20:Suppl. 1 (2015), 68–71.
51. Walker, M.M., Talley, N.J., et al. Review article: bacteria and pathogenesis of disease in the upper gastrointestinal tract–beyond the era of Helicobacter pylori. Aliment Pharmacol Ther 39:8 (2014), 767–779.
52. Sung, J., Kim, N., Kim, J., Jo, H.J., Park, J.H., Nam, R.H., et al. Comparison of gastric microbiota between gastric juice and mucosa by next generation sequencing method. J Cancer Prev 21:1 (2016), 60–65.
53. Hu, Y., He, L.H., Xiao, D., Liu, G.D., Gu, Y.X., Tao, X.X., et al. Bacterial flora concurrent with Helicobacter pylori in the stomach of patients with upper gastrointestinal diseases. World J Gastroenterol 18:11 (2012), 1257–1261.
54. Bik, E.M., Eckburg, P.B., Gill, S.R., Nelson, K.E., Purdom, E.A., Francois, F., et al. Molecular analysis of the bacterial microbiota in the human stomach. Proc Natl Acad Sci U. S. A 103:3 (2006), 732–737.
55. Khosravi, Y., Dieye, Y., Poh, B.H., Ng, C.G., Loke, M.F., Goh, K.L., et al. Culturable bacterial microbiota of the stomach of Helicobacter pylori positive and negative gastric disease patients. ScientificWorldJournal, 2014, 2014, 610421.
56. Andersson, A.F., Lindberg, M., Jakobsson, H., Backhed, F., Nyren, P., Engstrand, L., et al. Comparative analysis of human gut microbiota by barcoded pyrosequencing. PLoS One, 3(7), 2008, e2836.
57. Maldonado-Contreras, A., Goldfarb, K.C., Godoy-Vitorino, F., Karaoz, U., Contreras, M., Blaser, M.J., et al. Structure of the human gastric bacterial community in relation to Helicobacter pylori status. Isme J 5:4 (2011), 574–579.
58. Ferlay, J., Soerjomataram, I., Ervik, M., Dikshit, R., Eser, S., Mathers, C., et al. GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11. 2013, International Agency for Research on Cancer, Lyon, France Available from: http://globocan.iarc.fr.
59. Helicobacter and Cancer Collaborative Group. Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts. Gut 49:3 (2001), 347–353.
60. Uemura, N., Okamoto, S., Yamamoto, S., Matsumura, N., Yamaguchi, S., Yamakido, M., et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 345:11 (2001), 784–789.
61. Ma, J.L., Zhang, L., Brown, L.M., Li, J.Y., Shen, L., Pan, K.F., et al. Fifteen-year effects of Helicobacter pylori, garlic, and vitamin treatments on gastric cancer incidence and mortality. J Natl Cancer Inst 104:6 (2012), 488–492.
62. Polk, D.B., Peek, R.M. Jr., et al. Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer 10:6 (2010), 403–414.
63. Lofgren, J.L., Whary, M.T., Ge, Z., Muthupalani, S., Taylor, N.S., Mobley, M., et al. Lack of commensal flora in Helicobacter pylori-infected INS-GAS mice reduces gastritis and delays intraepithelial neoplasia. Gastroenterology 140:1 (2011), 210–220.
64. Lertpiriyapong, K., Whary, M.T., Muthupalani, S., Lofgren, J.L., Gamazon, E.R., Feng, Y., et al. Gastric colonisation with a restricted commensal microbiota replicates the promotion of neoplastic lesions by diverse intestinal microbiota in the Helicobacter pylori INS-GAS mouse model of gastric carcinogenesis. Gut 63:1 (2014), 54–63.
65. Dicksved, J., Lindberg, M., Rosenquist, M., Enroth, H., Jansson, J.K., Engstrand, L., et al. Molecular characterization of the stomach microbiota in patients with gastric cancer and in controls. J Med Microbiol 58:Pt 4 (2009), 509–516.
66. Han, H.S., Lee, K.Y., Lim, S.D., Kim, W.S., Hwang, T.S., et al. Molecular identification of Helicobacter DNA in human gastric adenocarcinoma tissues using Helicobacter species-specific 16S rRNA PCR amplification and pyrosequencing analysis. Oncol Lett 1:3 (2010), 555–558.
67. Jo, H.J., Kim, J., Kim, N., Park, J.H., Nam, R.H., Seok, Y.J., et al. Analysis of gastric microbiota by pyrosequencing: minor role of bacteria other than Helicobacter pylori in the gastric carcinogenesis. Helicobacter 21:5 (2016), 364–374.
68. Correa, P., et al. Human gastric carcinogenesis: a multistep and multifactorial process–first American cancer society Award lecture on cancer epidemiology and prevention. Cancer Res 52:24 (1992), 6735–6740.
69. Aviles-Jimenez, F., Vazquez-Jimenez, F., Medrano-Guzman, R., Mantilla, A., Torres, J., et al. Stomach microbiota composition varies between patients with non-atrophic gastritis and patients with intestinal type of gastric cancer. Sci Rep, 4, 2014, 4202.
70. Eun, C.S., Kim, B.K., Han, D.S., Kim, S.Y., Kim, K.M., Choi, B.Y., et al. Differences in gastric mucosal microbiota profiling in patients with chronic gastritis, intestinal metaplasia, and gastric cancer using pyrosequencing methods. Helicobacter 19:6 (2014), 407–416.
71. Wang, L., Zhou, J., Xin, Y., Geng, C., Tian, Z., Yu, X., et al. Bacterial overgrowth and diversification of microbiota in gastric cancer. Eur J Gastroenterol Hepatol 28:3 (2016), 261–266.
72. Li, T.H., Qin, Y., Sham, P.C., Lau, K.S., Chu, K.M., Leung, W.K., et al. Alterations in gastric microbiota after H. Pylori eradication and in different histological stages of gastric carcinogenesis. Sci Rep, 7, 2017, 44935.
73. Coker, O.O., Dai, Z., Nie, Y., Zhao, G., Cao, L., Nakatsu, G., et al. Mucosal microbiome dysbiosis in gastric carcinogenesis. Gut, 2017, 10.1136/gutjnl-2017-314281 [Epub ahead of print].
74. Seo, I., J, B.K., Suh, S.I., Suh, M.H., Baek, W.K., et al. Microbial profile of the stomach: comparison between normal mucosa and cancer tissue in the same patient. J Bacteriol Virol 44:2 (2014), 162–169.
75. He, C., Yang, Z., Lu, N., et al. Imbalance of gastrointestinal microbiota in the pathogenesis of Helicobacter pylori-Associated diseases. Helicobacter 21:5 (2016), 337–348.
76. Cao, L., Yu, J., et al. Effect of Helicobacter pylori infection on the composition of gastric microbiota in the development of gastric cancer. Gastrointest Tumors 2:1 (2015), 14–25.
77. Dias-Jacome, E., Libanio, D., Borges-Canha, M., Galaghar, A., Pimentel-Nunes, P., et al. Gastric microbiota and carcinogenesis: the role of non-Helicobacter pylori bacteria - a systematic review. Rev Esp Enferm Dig 108:9 (2016), 530–540.
78. Nardone, G., Compare, D., et al. The human gastric microbiota: is it time to rethink the pathogenesis of stomach diseases?. Unit Eur Gastroenterol J 3:3 (2015), 255–260.
79. Sheh, A., Fox, J.G., et al. The role of the gastrointestinal microbiome in Helicobacter pylori pathogenesis. Gut Microb 4:6 (2013), 505–531.
80. Li, G., Yang, M., Zhou, K., Zhang, L., Tian, L., Lv, S., et al. Diversity of duodenal and rectal microbiota in biopsy tissues and luminal contents in healthy volunteers. J Microbiol Biotechnol 25:7 (2015), 1136–1145.
81. Giamarellos-Bourboulis, E., Tang, J., Pyleris, E., Pistiki, A., Barbatzas, C., Brown, J., et al. Molecular assessment of differences in the duodenal microbiome in subjects with irritable bowel syndrome. Scand J Gastroenterol 50:9 (2015), 1076–1087.
82. Angelakis, E., Armougom, F., Carriere, F., Bachar, D., Laugier, R., Lagier, J.C., et al. A metagenomic investigation of the duodenal microbiota reveals links with obesity. PLoS One, 10(9), 2015, e0137784.
83. Wang, M., Ahrne, S., Jeppsson, B., Molin, G., et al. Comparison of bacterial diversity along the human intestinal tract by direct cloning and sequencing of 16S rRNA genes. FEMS Microbiol Ecol 54:2 (2005), 219–231.
84. Chung, C.S., Chang, P.F., Liao, C.H., Lee, T.H., Chen, Y., Lee, Y.C., et al. Differences of microbiota in small bowel and faeces between irritable bowel syndrome patients and healthy subjects. Scand J Gastroenterol 51:4 (2016), 410–419.
85. Hayashi, H., Takahashi, R., Nishi, T., Sakamoto, M., Benno, Y., et al. Molecular analysis of jejunal, ileal, caecal and recto-sigmoidal human colonic microbiota using 16S rRNA gene libraries and terminal restriction fragment length polymorphism. J Med Microbiol 54:Pt 11 (2005), 1093–1101.
86. Booijink, C.C., El-Aidy, S., Rajilic-Stojanovic, M., Heilig, H.G., Troost, F.J., Smidt, H., et al. High temporal and inter-individual variation detected in the human ileal microbiota. Environ Microbiol 12:12 (2010), 3213–3227.
87. Eckburg, P.B., Bik, E.M., Bernstein, C.N., Purdom, E., Dethlefsen, L., Sargent, M., et al. Diversity of the human intestinal microbial flora. Science 308:5728 (2005), 1635–1638.
88. Wang, X., Heazlewood, S.P., Krause, D.O., Florin, T.H., et al. Molecular characterization of the microbial species that colonize human ileal and colonic mucosa by using 16S rDNA sequence analysis. J Appl Microbiol 95:3 (2003), 508–520.
89. Hayashi, H., Sakamoto, M., Benno, Y., et al. Phylogenetic analysis of the human gut microbiota using 16S rDNA clone libraries and strictly anaerobic culture-based methods. Microbiol Immunol 46:8 (2002), 535–548.
90. Hayashi, H., Sakamoto, M., Kitahara, M., Benno, Y., et al. Molecular analysis of fecal microbiota in elderly individuals using 16S rDNA library and T-RFLP. Microbiol Immunol 47:8 (2003), 557–570.
91. Green, G.L., Brostoff, J., Hudspith, B., Michael, M., Mylonaki, M., Rayment, N., et al. Molecular characterization of the bacteria adherent to human colorectal mucosa. J Appl Microbiol 100:3 (2006), 460–469.
92. Delgado, S., Suarez, A., Mayo, B., et al. Identification of dominant bacteria in feces and colonic mucosa from healthy Spanish adults by culturing and by 16S rDNA sequence analysis. Dig Dis Sci 51:4 (2006), 744–751.
93. Hold, G.L., Pryde, S.E., Russell, V.J., Furrie, E., Flint, H.J., et al. Assessment of microbial diversity in human colonic samples by 16S rDNA sequence analysis. FEMS Microbiol Ecol 39:1 (2002), 33–39.
94. Lu, Y., Chen, J., Zheng, J., Hu, G., Wang, J., Huang, C., et al. Mucosal adherent bacterial dysbiosis in patients with colorectal adenomas. Sci Rep, 6, 2016, 26337.
95. Vogelstein, B., Kinzler, K.W., et al. The multistep nature of cancer. Trends Genet 9:4 (1993), 138–141.
96. Fearon, E.R., Vogelstein, B., et al. A genetic model for colorectal tumorigenesis. Cell 61:5 (1990), 759–767.
97. Sears, C.L., Pardoll, D.M., et al. Perspective: alpha-bugs, their microbial partners, and the link to colon cancer. J Infect Dis 203:3 (2011), 306–311.
98. Kuipers, E.J., de Jong, A., et al. [Gastrointestinal disorders and Streptococcus bovis bacteremia] Gastro-intestinale aandoeningen en Streptococcus bovis-bacteriemie. Ned Tijdschr Geneeskd 134:28 (1990), 1337–1339.
99. Nakatsu, G., Li, X., Zhou, H., Sheng, J., Wong, S.H., Wu, W.K., et al. Gut mucosal microbiome across stages of colorectal carcinogenesis. Nat Commun, 6, 2015, 8727.
100. Zhou, Y., He, H., Xu, H., Li, Y., Li, Z., Du, Y., et al. Association of oncogenic bacteria with colorectal cancer in South China. Oncotarget 7:49 (2016), 80794–80802.
101. Gao, Z., Guo, B., Gao, R., Zhu, Q., Qin, H., et al. Microbiota disbiosis is associated with colorectal cancer. Front Microbiol, 6, 2015, 20.
102. Flemer, B., Lynch, D.B., Brown, J.M., Jeffery, I.B., Ryan, F.J., Claesson, M.J., et al. Tumour-associated and non-tumour-associated microbiota in colorectal cancer. Gut 66:4 (2017), 633–643.
103. Tsoi, H., Chu, E.S.H., Zhang, X., Sheng, J., Nakatsu, G., Ng, S.C., et al. Peptostreptococcus anaerobius induces intracellular cholesterol biosynthesis in colon cells to induce proliferation and causes dysplasia in mice. Gastroenterology 152:6 (2017), 1419–1433 e5.
104. Gagniere, J., Raisch, J., Veziant, J., Barnich, N., Bonnet, R., Buc, E., et al. Gut microbiota imbalance and colorectal cancer. World J Gastroenterol 22:2 (2016), 501–518.
105. Hold, G.L., et al. Gastrointestinal Microbiota and Colon Cancer. Dig Dis 34:3 (2016), 244–250.
106. Sears, C.L., Garrett, W.S., et al. Microbes, microbiota, and colon cancer. Cell Host Microbe 15:3 (2014), 317–328.
107. Abreu, M.T., Peek, R.M. Jr., et al. Gastrointestinal malignancy and the microbiome. Gastroenterology 146:6 (2014), 1534–1546 e3.
108. Wroblewski, L.E., Peek, R.M. Jr., Coburn, L.A., et al. The role of the microbiome in gastrointestinal cancer. Gastroenterol Clin North Am 45:3 (2016), 543–556.
109. Hajishengallis, G., Darveau, R.P., Curtis, M.A., et al. The keystone-pathogen hypothesis. Nat Rev Microbiol 10:10 (2012), 717–725.
110. Han, Y.W., et al. Fusobacterium nucleatum: a commensal-turned pathogen. Curr Opin Microbiol 23 (2015), 141–147.
111. Castellarin, M., Warren, R.L., Freeman, J.D., Dreolini, L., Krzywinski, M., Strauss, J., et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res 22:2 (2012), 299–306.
112. Kostic, A.D., Gevers, D., Pedamallu, C.S., Michaud, M., Duke, F., Earl, A.M., et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res 22:2 (2012), 292–298.
113. Mima, K., Cao, Y., Chan, A.T., Qian, Z.R., Nowak, J.A., Masugi, Y., et al. Fusobacterium nucleatum in colorectal carcinoma tissue according to tumor location. Clin Transl Gastroenterol, 7(11), 2016, e200.
114. Shen, X.J., Rawls, J.F., Randall, T., Burcal, L., Mpande, C.N., Jenkins, N., et al. Molecular characterization of mucosal adherent bacteria and associations with colorectal adenomas. Gut Microb 1:3 (2010), 138–147.
115. Sanapareddy, N., Legge, R.M., Jovov, B., McCoy, A., Burcal, L., Araujo-Perez, F., et al. Increased rectal microbial richness is associated with the presence of colorectal adenomas in humans. Isme J 6:10 (2012), 1858–1868.
116. Marchesi, J.R., Dutilh, B.E., Hall, N., Peters, W.H., Roelofs, R., Boleij, A., et al. Towards the human colorectal cancer microbiome. PLoS One, 6(5), 2011, e20447.
117. Baxter, N.T., Ruffin, MTt, Rogers, M.A., Schloss, P.D., et al. Microbiota-based model improves the sensitivity of fecal immunochemical test for detecting colonic lesions. Genome Med, 8(1), 2016, 37.
118. Zhou, Y.J., Zhao, D.D., Liu, H., Chen, H.T., Li, J.J., Mu, X.Q., et al. Cancer killers in the human gut microbiota: diverse phylogeny and broad spectra. Oncotarget 8:30 (2017), 49574–49591.
119. Eppinga, H., Fuhler, G.M., Peppelenbosch, M.P., Hecht, G.A., et al. Gut microbiota developments with emphasis on inflammatory bowel disease: report from the gut microbiota for health world summit 2016. Gastroenterology 151:2 (2016), e1–4.
120. Eppinga, H., Poortinga, S., Thio, H.B., Nijsten, T.E.C., Nuij, V., van der Woude, C.J., et al. Prevalence and phenotype of concurrent psoriasis and inflammatory bowel disease. Inflamm Bowel Dis, 2017, 10.1097/MIB.0000000000001169 [Epub ahead of print].
121. Deuring, J.J., Fuhler, G.M., Konstantinov, S.R., Peppelenbosch, M.P., Kuipers, E.J., de Haar, C., et al. Genomic ATG16L1 risk allele-restricted Paneth cell ER stress in quiescent Crohn's disease. Gut 63:7 (2014), 1081–1091.
122. Eppinga, H., Thio, H.B., Schreurs, M.W.J., Blakaj, B., Tahitu, R.I., Konstantinov, S.R., et al. Depletion of Saccharomyces cerevisiae in psoriasis patients, restored by Dimethylfumarate therapy (DMF). PLoS One, 12(5), 2017, e0176955.
123. Zackular, J.P., Rogers, M.A., Ruffin, MTt, Schloss, P.D., et al. The human gut microbiome as a screening tool for colorectal cancer. Cancer Prev Res (Phila) 7:11 (2014), 1112–1121.
124. Zeller, G., Tap, J., Voigt, A.Y., Sunagawa, S., Kultima, J.R., Costea, P.I., et al. Potential of fecal microbiota for early-stage detection of colorectal cancer. Mol Syst Biol, 10, 2014, 766.
125. Yu, J., Feng, Q., Wong, S.H., Zhang, D., Liang, Q.Y., Qin, Y., et al. Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut 66:1 (2017), 70–78.
126. Liang, Q., Chiu, J., Chen, Y., Huang, Y., Higashimori, A., Fang, J., et al. Fecal bacteria act as novel biomarkers for noninvasive diagnosis of colorectal cancer. Clin Cancer Res 23:8 (2017), 2061–2070.
127. Wong, S.H., Kwong, T.N.Y., Chow, T.C., Luk, A.K.C., Dai, R.Z.W., Nakatsu, G., et al. Quantitation of faecal Fusobacterium improves faecal immunochemical test in detecting advanced colorectal neoplasia. Gut 66:8 (2017), 1441–1448.
128. Baxter, N.T., Koumpouras, C.C., Rogers, M.A., Ruffin, MTt, Schloss, P.D., et al. DNA from fecal immunochemical test can replace stool for detection of colonic lesions using a microbiota-based model. Microbiome, 4(1), 2016, 59.
129. Louis, P., Hold, G.L., Flint, H.J., et al. The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev Microbiol 12:10 (2014), 661–672.
130. Borges-Canha, M., Portela-Cidade, J.P., Dinis-Ribeiro, M., Leite-Moreira, A.F., Pimentel-Nunes, P., et al. Role of colonic microbiota in colorectal carcinogenesis: a systematic review. Rev Esp Enferm Dig 107:11 (2015), 659–671.
131. Chen, W., Liu, F., Ling, Z., Tong, X., Xiang, C., et al. Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer. PLoS One, 7(6), 2012, e39743.
132. Smith, B.C., Zolnik, C.P., Usyk, M., Chen, Z., Kaiser, K., Nucci-Sack, A., et al. Distinct ecological niche of anal, oral, and cervical mucosal microbiomes in adolescent women. Yale J Biol Med 89:3 (2016), 277–284.
133. Yu, G., Fadrosh, D., Ma, B., Ravel, J., Goedert, J.J., et al. Anal microbiota profiles in HIV-positive and HIV-negative MSM. Aids 28:5 (2014), 753–760.
134. Hoekstra, E., Das, A.M., Swets, M., Cao, W., van der Woude, C.J., Bruno, M.J., et al. Increased PTP1B expression and phosphatase activity in colorectal cancer results in a more invasive phenotype and worse patient outcome. Oncotarget 7:16 (2016), 21922–21938.
135. Fuhler, G.M., Tyl, M.R., Olthof, S.G., Lyndsay Drayer, A., Blom, N., Vellenga, E., et al. Distinct roles of the mTOR components Rictor and Raptor in MO7e megakaryocytic cells. Eur J Haematol 83:3 (2009), 235–245.
136. Queiroz, K.C., Milani, R., Ruela-de-Sousa, R.R., Fuhler, G.M., Justo, G.Z., Zambuzzi, W.F., et al. Violacein induces death of resistant leukaemia cells via kinome reprogramming, endoplasmic reticulum stress and Golgi apparatus collapse. PLoS One, 7(10), 2012, e45362.
137. Brawner, K.M., Morrow, C.D., Smith, P.D., et al. Gastric microbiome and gastric cancer. Cancer J 20:3 (2014), 211–216.
138. Naylor, G., Axon, A., et al. Role of bacterial overgrowth in the stomach as an additional risk factor for gastritis. Can J Gastroenterol, 17(Suppl B), 2003 13B-7B.
139. Jakszyn, P., Bingham, S., Pera, G., Agudo, A., Luben, R., Welch, A., et al. Endogenous versus exogenous exposure to N-nitroso compounds and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST) study. Carcinogenesis 27:7 (2006), 1497–1501.
140. Lundberg, J.O., Weitzberg, E., Lundberg, J.M., Alving, K., et al. Intragastric nitric oxide production in humans: measurements in expelled air. Gut 35:11 (1994), 1543–1546.
141. Reed, P.I., Smith, P.L., Haines, K., House, F.R., Walters, C.L., et al. Gastric juice N-nitrosamines in health and gastroduodenal disease. Lancet 2:8246 (1981), 550–552.
142. Ruddell, W.S., Bone, E.S., Hill, M.J., Blendis, L.M., Walters, C.L., et al. Gastric-juice nitrite. A risk factor for cancer in the hypochlorhydric stomach?. Lancet 2:7994 (1976), 1037–1039.
143. Schlag, P., Bockler, R., Peter, M., et al. Nitrite and nitrosamines in gastric juice: risk factors for gastric cancer?. Scand J Gastroenterol 17:1 (1982), 145–150.
144. Kodama, K., Sumii, K., Kawano, M., Kido, T., Nojima, K., Sumii, M., et al. Gastric juice nitrite and vitamin C in patients with gastric cancer and atrophic gastritis: is low acidity solely responsible for cancer risk?. Eur J Gastroenterol Hepatol 15:9 (2003), 987–993.
145. Tseng, C.H., Lin, J.T., Ho, H.J., Lai, Z.L., Wang, C.B., Tang, S.L., et al. Gastric microbiota and predicted gene functions are altered after subtotal gastrectomy in patients with gastric cancer. Sci Rep, 6, 2016, 20701.
146. Fukata, M., Abreu, M.T., et al. Role of Toll-like receptors in gastrointestinal malignancies. Oncogene 27:2 (2008), 234–243.
147. Castano-Rodriguez, N., Kaakoush, N.O., Mitchell, H.M., et al. Pattern-recognition receptors and gastric cancer. Front Immunol, 5, 2014, 336.
148. Pimentel-Nunes, P., Afonso, L., Lopes, P., Roncon-Albuquerque, R. Jr., Goncalves, N., Henrique, R., et al. Increased expression of toll-like receptors (TLR) 2, 4 and 5 in gastric dysplasia. Pathol Oncol Res 17:3 (2011), 677–683.
149. Pimentel-Nunes, P., Goncalves, N., Boal-Carvalho, I., Afonso, L., Lopes, P., Roncon-Albuquerque, R. Jr., et al. Helicobacter pylori induces increased expression of Toll-like receptors and decreased Toll-interacting protein in gastric mucosa that persists throughout gastric carcinogenesis. Helicobacter 18:1 (2013), 22–32.
150. Schmausser, B., Andrulis, M., Endrich, S., Muller-Hermelink, H.K., Eck, M., et al. Toll-like receptors TLR4, TLR5 and TLR9 on gastric carcinoma cells: an implication for interaction with Helicobacter pylori. Int J Med Microbiol 295:3 (2005), 179–185.
151. Wu, S., Powell, J., Mathioudakis, N., Kane, S., Fernandez, E., Sears, C.L., et al. Bacteroides fragilis enterotoxin induces intestinal epithelial cell secretion of interleukin-8 through mitogen-activated protein kinases and a tyrosine kinase-regulated nuclear factor-kappaB pathway. Infect Immun 72:10 (2004), 5832–5839.
152. Goodwin, A.C., Destefano Shields, C.E., Wu, S., Huso, D.L., Wu, X., Murray-Stewart, T.R., et al. Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis. Proc Natl Acad Sci U. S. A 108:37 (2011), 15354–15359.
153. Nougayrede, J.P., Homburg, S., Taieb, F., Boury, M., Brzuszkiewicz, E., Gottschalk, G., et al. Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science 313:5788 (2006), 848–851.
154. Dalmasso, G., Cougnoux, A., Delmas, J., Darfeuille-Michaud, A., Bonnet, R., et al. The bacterial genotoxin colibactin promotes colon tumor growth by modifying the tumor microenvironment. Gut Microb 5:5 (2014), 675–680.
155. Rubinstein, M.R., Wang, X., Liu, W., Hao, Y., Cai, G., Han, Y.W., et al. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/beta-catenin signaling via its FadA adhesin. Cell Host Microbe 14:2 (2013), 195–206.
156. Pimentel-Nunes, P., Goncalves, N., Boal-Carvalho, I., Afonso, L., Lopes, P., Roncon-Albuquerque, R. Jr., et al. Decreased Toll-interacting protein and peroxisome proliferator-activated receptor gamma are associated with increased expression of Toll-like receptors in colon carcinogenesis. J Clin Pathol 65:4 (2012), 302–308.
157. Li, T.T., Ogino, S., Qian, Z.R., et al. Toll-like receptor signaling in colorectal cancer: carcinogenesis to cancer therapy. World J Gastroenterol 20:47 (2014), 17699–17708.
158. Pimentel-Nunes, P., Teixeira, A.L., Pereira, C., Gomes, M., Brandao, C., Rodrigues, C., et al. Functional polymorphisms of Toll-like receptors 2 and 4 alter the risk for colorectal carcinoma in Europeans. Dig Liver Dis 45:1 (2013), 63–69.
159. Nagao-Kitamoto, H., Kitamoto, S., Kuffa, P., Kamada, N., et al. Pathogenic role of the gut microbiota in gastrointestinal diseases. Intest Res 14:2 (2016), 127–138.
160. Anand, S., Kaur, H., Mande, S.S., et al. Comparative in silico analysis of butyrate production pathways in gut commensals and pathogens. Front Microbiol, 7, 2016, 1945.
161. Ou, J., Carbonero, F., Zoetendal, E.G., DeLany, J.P., Wang, M., Newton, K., et al. Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans. Am J Clin Nutr 98:1 (2013), 111–120.
162. Li, S., Konstantinov, S.R., Smits, R., Peppelenbosch, M.P., et al. Bacterial biofilms in colorectal cancer initiation and progression. Trends Mol Med 23:1 (2017), 18–30.