Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

A bacterial driver–passenger model for colorectal cancer: beyond the usual suspects

Nature Reviews Microbiology volume 10, pages 575–582 (2012)Cite this article

Subjects

Abstract

Cancer has long been considered a genetic disease. However, accumulating evidence supports the involvement of infectious agents in the development of cancer, especially in those organs that are continuously exposed to microorganisms, such as the large intestine. Recent next-generation sequencing studies of the intestinal microbiota now offer an unprecedented view of the aetiology of sporadic colorectal cancer and have revealed that the microbiota associated with colorectal cancer contains bacterial species that differ in their temporal associations with developing tumours. Here, we propose a bacterial driver–passenger model for microbial involvement in the development of colorectal cancer and suggest that this model be incorporated into the genetic paradigm of cancer progression.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Colorectal cancer-associated microbiomes.
Figure 2: A bacterial driver–passenger model for colorectal cancer.
Figure 3: Interaction-dependent colonization of the intestinal epithelium.

References

  1. Stratton, M. R., Campbell, P. J. & Futreal, P. A. The cancer genome. Nature 458, 719–724 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Esteller, M. Cancer epigenomics: DNA methylomes and histone-modification maps. Nature Rev. Genet. 8, 286–298 (2007).

    Article  CAS  PubMed  Google Scholar 

  3. Dalton-Griffin, L. & Kellam, P. Infectious causes of cancer and their detection. J. Biol. 8, 67 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. zur Hausen, H. The search for infectious causes of human cancers: where and why (Nobel lecture). Angew. Chem. Int. Ed. Engl. 48, 5798–5808 (2009).

    Article  CAS  PubMed  Google Scholar 

  5. Warren, J. R. Helicobacter: the ease and difficulty of a new discovery (Nobel lecture). Chem. Med. Chem. 1, 672–685 (2006).

    Article  CAS  PubMed  Google Scholar 

  6. Qin, J. J. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 59–65 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Dethlefsen, L., Eckburg, P. B., Bik, E. M. & Relman, D. A. Assembly of the human intestinal microbiota. Trends Ecol. Evol. 21, 517–523 (2006).

    Article  PubMed  Google Scholar 

  8. Claesson, M. J. et al. Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc. Natl Acad. Sci. USA 108 (Suppl. 1), 4586–4591 (2011).

    Article  CAS  PubMed  Google Scholar 

  9. Marchesi, J. R. Human distal gut microbiome. Environ. Microbiol. 13, 3088–3102 (2011).

    Article  PubMed  Google Scholar 

  10. Proctor, L. M. The human microbiome project in 2011 and beyond. Cell Host Microbe 10, 287–291 (2011).

    Article  CAS  PubMed  Google Scholar 

  11. Jemal, A. et al. Cancer statistics, 2009. CA Cancer J. Clin. 59, 225–249 (2009).

    Article  PubMed  Google Scholar 

  12. Dove, W. F. et al. Intestinal neoplasia in the ApcMin mouse: independence from the microbial and natural killer (beige locus) status. Cancer Res. 57, 812–814 (1997).

    CAS  PubMed  Google Scholar 

  13. Sellon, R. K. et al. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect. Immun. 66, 5224–5231 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Uronis, J. M. et al. Modulation of the intestinal microbiota alters colitis-associated colorectal cancer susceptibility. PLoS ONE 4, e6026 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Vogelstein, B. & Kinzler, K. W. The multistep nature of cancer. Trends Genet. 9, 138–141 (1993).

    Article  CAS  PubMed  Google Scholar 

  16. Ferlay, J. et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int. J. Cancer 127, 2893–2917 (2010).

    Article  CAS  PubMed  Google Scholar 

  17. Watson, A. J. & Collins, P. D. Colon cancer: a civilization disorder. Dig. Dis. 29, 222–228 (2011).

    Article  PubMed  Google Scholar 

  18. Fearon, E. R. Molecular genetics of colorectal cancer. Annu. Rev. Pathol. 6, 479–507 (2011).

    Article  CAS  PubMed  Google Scholar 

  19. Barker, N. et al. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457, 608–611 (2009).

    Article  CAS  PubMed  Google Scholar 

  20. Ricci-Vitiani, L., Fabrizi, E., Palio, E. & De Maria, R. Colon cancer stem cells. J. Mol. Med. 87, 1097–1104 (2009).

    Article  PubMed  Google Scholar 

  21. Lakatos, P. L. & Lakatos, L. Risk for colorectal cancer in ulcerative colitis: changes, causes and management strategies. World J. Gastroenterol. 14, 3937–3947 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Phelps, R. A., Broadbent, T. J., Stafforini, D. M. & Jones, D. A. New perspectives on APC control of cell fate and proliferation in colorectal cancer. Cell Cycle 8, 2549–2556 (2009).

    Article  CAS  PubMed  Google Scholar 

  23. Reya, T. & Clevers, H. Wnt signalling in stem cells and cancer. Nature 434, 843–850 (2005).

    Article  CAS  PubMed  Google Scholar 

  24. Sheng, H. et al. Nuclear translocation of β-catenin in hereditary and carcinogen-induced intestinal adenomas. Carcinogenesis 19, 543–549 (1998).

    Article  CAS  PubMed  Google Scholar 

  25. Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011).

    Article  CAS  PubMed  Google Scholar 

  26. Marchesi, J. R. et al. Towards the human colorectal cancer microbiome. PLoS ONE 6, e20447 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kostic, A. D. et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 22, 292–298 (2011).

    Article  CAS  PubMed  Google Scholar 

  28. Castellarin, M. et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 22, 299–306 (2011).

    Article  CAS  PubMed  Google Scholar 

  29. Sears, C. L. & Pardoll, D. M. Perspective: alpha-bugs, their microbial partners, and the link to colon cancer. J. Infect. Dis. 203, 306–311 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Gill, S. R. et al. Metagenomic analysis of the human distal gut microbiome. Science 312, 1355–1359 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Eckburg, P. B. et al. Diversity of the human intestinal microbial flora. Science 308, 1635–1638 (2005).

    PubMed  PubMed Central  Google Scholar 

  32. Green, G. L. et al. Molecular characterization of the bacteria adherent to human colorectal mucosa. J. Appl. Microbiol. 100, 460–469 (2006).

    Article  CAS  PubMed  Google Scholar 

  33. Costello, E. K. et al. Bacterial community variation in human body habitats across space and time. Science 326, 1694–1697 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Rajilić-Stojanović, M., Smidt, H. & de Vos, W. M. Diversity of the human gastrointestinal tract microbiota revisited. Environ. Microbiol. 9, 2125–2136 (2007).

    Article  PubMed  Google Scholar 

  35. Turnbaugh, P. J. & Gordon, J. I. The core gut microbiome, energy balance and obesity. J. Physiol. 587, 4153–4158 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Arumugam, M. et al. Enterotypes of the human gut microbiome. Nature 473, 174–180 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hong, P. Y., Croix, J. A., Greenberg, E., Gaskins, H. R. & Mackie, R. I. Pyrosequencing-based analysis of the mucosal microbiota in healthy individuals reveals ubiquitous bacterial groups and micro-heterogeneity. PLoS ONE 6, e25042 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Boleij, A. & Tjalsma, H. Gut bacteria in health and disease: a survey on the interface between intestinal microbiology and colorectal cancer. Biol. Rev. Camb. Philos. Soc. 2 Feb 2012 (doi:10.1111/j.1469-185X.2012.00218.x).

    Article  PubMed  Google Scholar 

  39. Huycke, M. M., Abrams, V. & Moore, D. R. Enterococcus faecalis produces extracellular superoxide and hydrogen peroxide that damages colonic epithelial cell DNA. Carcinogenesis 23, 529–536 (2002).

    Article  CAS  PubMed  Google Scholar 

  40. Wang, X. M. & Huycke, M. M. Extracellular superoxide production by Enterococcus faecalis promotes chromosomal instability in mammalian cells. Gastroenterology 132, 551–561 (2007).

    Article  CAS  PubMed  Google Scholar 

  41. Wang, X. M. et al. Enterococcus faecalis induces aneuploidy and tetraploidy in colonic epithelial cells through a bystander effect. Cancer Res. 68, 9909–9917 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Nougayrède, J. P. et al. Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science 313, 848–851 (2006).

    Article  CAS  PubMed  Google Scholar 

  43. Cuevas-Ramos, G. et al. Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells. Proc. Natl Acad. Sci. USA 107, 11537–11542 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Wu, S. et al. The Bacteroides fragilis toxin binds to a specific intestinal epithelial cell receptor. Infect. Immun. 74, 5382–5390 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Toprak, N. U. et al. A possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer. Clin. Microbiol. Infect. 12, 782–786 (2006).

    Article  CAS  PubMed  Google Scholar 

  46. Goodwin, A. C. et al. Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis. Proc. Natl Acad. Sci. USA 108, 15354–15359 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Wu, S., Rhee, K. J., Zhang, M., Franco, A. & Sears, C. L. Bacteroides fragilis toxin stimulates intestinal epithelial cell shedding and gamma-secretase-dependent E-cadherin cleavage. J. Cell Sci. 120, 1944–1952 (2007).

    Article  CAS  PubMed  Google Scholar 

  48. Wu, S. G. et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nature Med. 15, 1016–1022 (2009).

    Article  CAS  PubMed  Google Scholar 

  49. Housseau, F. & Sears, C. L. Enterotoxigenic Bacteroides fragilis (ETBF)-mediated colitis in Min (Apc+/−) mice: a human commensal-based murine model of colon carcinogenesis. Cell Cycle 9, 3–5 (2010).

    Article  CAS  PubMed  Google Scholar 

  50. Mangan, P. R. et al. Transforming growth factor-β induces development of the TH17 lineage. Nature 441, 231–234 (2006).

    CAS  PubMed  Google Scholar 

  51. DuPont, H. L. Bacterial diarrhea. N. Engl. J. Med. 361, 1560–1569 (2009).

    Article  CAS  PubMed  Google Scholar 

  52. Maggio-Price, L. et al. Bacterial infection of Smad3/Rag2 double-null mice with transforming growth factor-β dysregulation as a model for studying inflammation-associated colon cancer. Am. J. Pathol. 174, 317–329 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ahmed, S. et al. Mucosa-associated bacterial diversity in relation to human terminal ileum and colonic biopsy samples. Appl. Environ. Microbiol. 73, 7435–7442 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Shen, X. et al. Molecular characterization of mucosal adherent bacteria and associations with colorectal adenomas. Gut Microbes 1, 138–147 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Hirayama, A. et al. Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry. Cancer Res. 69, 4918–4925 (2009).

    Article  CAS  PubMed  Google Scholar 

  56. Klein, R. S. et al. Association of Streptococcus bovis with carcinoma of the colon. N. Engl. J. Med. 297, 800–802 (1977).

    Article  CAS  PubMed  Google Scholar 

  57. Boleij, A., van Gelder, M. M., Swinkels, D. W. & Tjalsma, H. Clinical Importance of Streptococcus gallolyticus infection among colorectal cancer patients: systematic review and meta-analysis. Clin. Infect. Dis. 53, 870–878 (2011).

    Article  CAS  PubMed  Google Scholar 

  58. Boleij, A. et al. Selective antibody response to Streptococcus gallolyticus pilus proteins in colorectal cancer patients. Cancer Prev. Res. 5, 260–265 (2012).

    Article  Google Scholar 

  59. Tjalsma, H. & Boleij, A. Subtyping of Streptococcus bovis group bacteria is needed to fully understand the clinical value of Streptococcus gallolyticus (S. bovis biotype I) infection as early sign of colonic malignancy. Int. J. Clin. Pract. 66, 326 (2012).

    Article  CAS  PubMed  Google Scholar 

  60. Boleij, A. et al. Novel clues on the specific association of Streptococcus gallolyticus subsp gallolyticus with colorectal cancer. J. Infect. Dis. 203, 1101–1109 (2011).

    Article  CAS  PubMed  Google Scholar 

  61. Vanrobaeys, M., De Herdt, P., Charlier, G., Ducatelle, R. & Haesebrouck, F. Ultrastructure of surface components of Streptococcus gallolytics (S. bovis) strains of differing virulence isolated from pigeons. Microbiology 145, 335–342 (1999).

    Article  CAS  PubMed  Google Scholar 

  62. Rusniok, C. et al. Genome sequence of Streptococcus gallolyticus: insights into its adaptation to the bovine rumen and its ability to cause endocarditis. J. Bacteriol. 192, 2266–2276 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Haimowitz, M. D., Hernandez, L. A. & Herron, R. M. A blood donor with bacteraemia. Lancet 365, 1596 (2005).

    Article  PubMed  Google Scholar 

  64. Wentling, G. K., Metzger, P. P., Dozois, E. J., Chua, H. K. & Krishna, M. Unusual bacterial infections and colorectal carcinoma—Streptococcus bovis and Clostridium septicum: report of three cases. Dis. Colon Rectum 49, 1223–1227 (2006).

    Article  PubMed  Google Scholar 

  65. Corredoira, J., Alonso, M. P., Pita, J. & Alonso-Mesonero, D. Association between rural residency, group D streptococcal endocarditis and colon cancer? Clin. Microbiol. Infect. 14, 190 (2008).

    Article  CAS  PubMed  Google Scholar 

  66. Boleij, A. et al. Increased exposure to bacterial antigen RpL7/L12 in early stage colorectal cancer patients. Cancer 116, 4014–4022 (2010).

    Article  CAS  PubMed  Google Scholar 

  67. Abdulamir, A. S., Hafidh, R. R. & Bakar, F. A. Molecular detection, quantification, and isolation of Streptococcus gallolyticus bacteria colonizing colorectal tumors: inflammation-driven potential of carcinogenesis via IL-1, COX-2, and IL-8. Mol. Cancer 9, 249 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Ellmerich, S. et al. Promotion of intestinal carcinogenesis by Streptococcus bovis. Carcinogenesis 21, 753–756 (2000).

    Article  CAS  PubMed  Google Scholar 

  69. Tjalsma, H. et al. Profiling the humoral immune response in colon cancer patients: diagnostic antigens from Streptococcus bovis. Int. J. Cancer 119, 2127–2135 (2006).

    Article  CAS  PubMed  Google Scholar 

  70. Jin, J. S., Kitahara, M., Sakamoto, M., Hattori, M. & Benno, Y. Slackia equolifaciens sp. nov., a human intestinal bacterium capable of producing equol. Int. J. Syst. Evol. Microbiol. 60, 1721–1724 (2010).

    Article  CAS  PubMed  Google Scholar 

  71. Hamer, H. M. et al. Review article: the role of butyrate on colonic function. Aliment. Pharmacol. Ther. 27, 104–119 (2008).

    Article  CAS  PubMed  Google Scholar 

  72. Choi, E. J., Ahn, W. S. & Bae, S. M. Equol induces apoptosis through cytochrome c-mediated caspases cascade in human breast cancer MDA-MB-453 cells. Chem. Biol. Interact. 177, 7–11 (2009).

    Article  CAS  PubMed  Google Scholar 

  73. Davis, C. D. & Milner, J. A. Gastrointestinal microflora, food components and colon cancer prevention. J. Nutr. Biochem. 20, 743–752 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Bordonaro, M., Lazarova, D. L. & Sartorelli, A. C. Butyrate and Wnt signaling: a possible solution to the puzzle of dietary fiber and colon cancer risk? Cell Cycle 7, 1178–1183 (2008).

    Article  CAS  PubMed  Google Scholar 

  75. Phelps, R. A. et al. A two-step model for colon adenoma initiation and progression caused by APC loss. Cell 137, 623–634 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Kang, H. Y. et al. Progression of atrophic gastritis and intestinal metaplasia drives Helicobacter pylori out of the gastric mucosa. Dig. Dis. Sci. 51, 2310–2315 (2006).

    Article  PubMed  Google Scholar 

  77. Sears, C. L. et al. Association of enterotoxigenic Bacteroides fragilis infection with inflammatory diarrhea. Clin. Infect. Dis. 47, 797–803 (2008).

    Article  CAS  PubMed  Google Scholar 

  78. Sears, C. L. Enterotoxigenic Bacteroides fragilis: a rogue among symbiotes. Clin. Microbiol. Rev. 22, 349–369 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Blaschitz, C. & Raffatellu, M. Th17 cytokines and the gut mucosal barrier. J. Clin. Immunol. 30, 196–203 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Goto, Y. & Kiyono, H. Epithelial barrier: an interface for the cross-communication between gut flora and immune system. Immunol. Rev. 245, 147–163 (2012).

    Article  CAS  PubMed  Google Scholar 

  81. Skaar, E. P. The battle for iron between bacterial pathogens and their vertebrate hosts. PLoS Pathog. 6, e1000949 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Kolenbrander, P. E., Palmer, R. J., Periasamy, S. & Jakubovics, N. S. Oral multispecies biofilm development and the key role of cell-cell distance. Nature Rev. Microbiol. 8, 471–480 (2010).

    Article  CAS  Google Scholar 

  83. Kaplan, C. W., Lux, R., Haake, S. K. & Shi, W. The Fusobacterium nucleatum outer membrane protein RadD is an arginine-inhibitable adhesin required for inter-species adherence and the structured architecture of multispecies biofilm. Mol. Microbiol. 71, 35–47 (2009).

    Article  CAS  PubMed  Google Scholar 

  84. Smith, P. et al. Host genetics and environmental factors regulate ecological succession of the mouse colon tissue-associated microbiota. PLoS ONE 7, e30273 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Strauss, J. et al. Invasive potential of gut mucosa-derived fusobacterium nucleatum positively correlates with IBD status of the host. Inflamm. Bowel Dis. 17, 1971–1978 (2011).

    Article  PubMed  Google Scholar 

  86. Walker, A. W. et al. Dominant and diet-responsive groups of bacteria within the human colonic microbiota. ISME J. 5, 220–230 (2011).

    Article  CAS  PubMed  Google Scholar 

  87. Lieberman, D. Clinical practice. Screening for colorectal cancer. N. Engl. J. Med. 361, 1179–1187 (2009).

    Article  CAS  PubMed  Google Scholar 

  88. Tjalsma, H. Identification of biomarkers for colorectal cancer through proteomics-based approaches. Expert Rev. Proteomics 7, 879–895 (2010).

    Article  CAS  PubMed  Google Scholar 

  89. Allen-Vercoe, E., Strauss, J. & Chadee, K. Fusobacterium nucleatum: an emerging gut pathogen? Gut Microbes 2, 294–298 (2011).

    Article  PubMed  Google Scholar 

  90. He, X. et al. Adherence to streptococci facilitates Fusobacterium nucleatum integration into an oral microbial community. Microb. Ecol. 63, 532–542 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  91. Kapatral, V. et al. Genome sequence and analysis of the oral bacterium Fusobacterium nucleatum strain ATCC 25586. J. Bacteriol. 184, 2005–2018 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank R. Roelofs, G. Kortman and I. Kato for inspiring discussions and the three anonymous referees for their excellent suggestions, which were very useful in shaping the final article. This work was in part supported by the Dutch Cancer Society (KWF; Project KUN 2006–3591) and the Dutch Digestive Diseases Foundation (MDLS; project WO 10–53). B.E.D. was supported by the Dutch Science foundation (NWO; Veni grant 016.111.075). The funding bodies had no role in the study design, data collection and analysis, the decision to publish or the preparation of the manuscript.

Author information

Author notes

  1. Annemarie Boleij

    Present address: Annemarie Boleij was previously at the Department of Laboratory Medicine, N4i & RUCO, Radboud University Medical Centre, Nijmegen, The Netherlands. Present address: Department of Medicine, Johns Hopkins University School of Medicine, 1550 Orleans Street, Baltimore, Maryland 21231, USA.,

Authors and Affiliations

  1. Harold Tjalsma is at the Department of Laboratory Medicine, Nijmegen Institute for Infection, Inflammation and Immunity (N4i) & Radboud University Centre for Oncology (RUCO), Radboud University Medical Centre, Geert Grooteplein 10 (830), 6525 GA Nijmegen, The Netherlands.,

    Harold Tjalsma

  2. Julian R. Marchesi is at the School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AT, United Kingdom.,

    Julian R. Marchesi

  3. and at the Departments of Computer Science and Biology, Bas E. Dutilh is at the Centre for Molecular and Biomolecular Informatics, Nijmegen Centre for Molecular Life Sciences, Radboud University Medical Centre, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands, San Diego State University, San Diego, California 92182, USA.,

    Bas E. Dutilh

Authors
  1. Harold Tjalsma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Annemarie Boleij
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Julian R. Marchesi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bas E. Dutilh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Harold Tjalsma or Julian R. Marchesi.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Glossary

Colonic dysbiosis

A local or disseminated change in the composition of the colonic microbiota, often leading to impaired health. Dysbiosis may be either the cause or the consequence of intestinal disease.

Commensal bacteria

Bacteria living in a mutually advantageous relationship with a host (for example, in the lumen of the gastrointestinal tract).

COX2 pathway

The regulatory pathway responsible for the formation of important biological regulator molecules, including prostaglandins. The enzyme COX2 is not detectable in most healthy tissues but is upregulated during inflammation and in carcinomas. Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, inhibit the COX2 pathway and decrease the risk of colorectal cancer development.

CXC-chemokines

A subfamily of chemokines that contain a Cys-Xaa-Cys motif. Chemokines are small secreted molecules that function in leukocyte recruitment and activation, and react to different pathological processes, including infectious disease, inflammation and tumorigenesis.

Dysplasia

An abnormal proliferation of immature cells.

Epigenetic mutations

Functionally relevant modifications of the genome that do not involve a change in the nucleotide sequence; for example, changes in DNA methylation or histone deacetylation.

Genotoxin

A compound that is capable of causing damage to, or genetic mutations in, DNA; also known as a mutagenic or carcinogenic compound.

Hyperplasia

A site (within an organ) that has an increased number of cells or an increase in cell proliferation, representing the early phases of a tumour; also known as a neoplasia, a pre-malignant lesion or a benign tumour.

Metatranscriptome

All of the genetic transcripts (RNA) within a microbiota.

Microbiome

All of the genetic material (DNA) within a microbiota. This can also be referred to as the metagenome of the microbiota.

Microbiota

The complete setof microorganisms that are present in a particular environment or community.

Probiotic organisms

Microorganisms that have effects which are thought to be beneficial to the health of the host when the microorganism in question is present in adequate amounts.

Prebiotics

Growth substrates that are preferentially (or ideally, exclusively) metabolized by a single probiotic genus or species and may thus be used as dietary supplements to promote targeted growth of these microorganisms.

Tumorigenesis

The process by which a new tumour is produced.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Tjalsma, H., Boleij, A., Marchesi, J. et al. A bacterial driver–passenger model for colorectal cancer: beyond the usual suspects. Nat Rev Microbiol 10, 575–582 (2012). https://doi.org/10.1038/nrmicro2819

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrmicro2819

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research