Fusobacterium nucleatum — symbiont, opportunist and oncobacterium

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Fusobacterium nucleatum has long been found to cause opportunistic infections and has recently been implicated in colorectal cancer; however, it is a common member of the oral microbiota and can have a symbiotic relationship with its hosts. To address this dissonance, we explore the diversity and niches of fusobacteria and reconsider historic fusobacterial taxonomy in the context of current technology. We also undertake a critical reappraisal of fusobacteria with a focus on F. nucleatum as a mutualist, infectious agent and oncogenic microorganism. In this Review, we delve into recent insights and future directions for fusobacterial research, including the current genetic toolkit, our evolving understanding of its mechanistic role in promoting colorectal cancer and the challenges of developing diagnostics and therapeutics for F. nucleatum.

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Fig. 1: The organizing role of Fusobacterium nucleatum in oral biofilms.
Fig. 2: Oral and extraoral diseases associated with Fusobacterium nucleatum.
Fig. 3: Mechanisms by which Fusobacterium nucleatum may contribute to colorectal carcinogenesis.


  1. 1.

    Hug, L. A. et al. A new view of the tree of life. Nat. Microbiol. 1, 16048 (2016).

  2. 2.

    Parks, D. H. et al. Recovery of nearly 8,000 metagenome-assembled genomes substantially expands the tree of life. Nat. Microbiol. 2, 1533–1542 (2017).

  3. 3.

    Zhao, J.-S., Manno, D. & Hawari, J. Psychrilyobacter atlanticus gen. nov., sp. nov., a marine member of the phylum Fusobacteria that produces H2 and degrades nitramine explosives under low temperature conditions. Int. J. Syst. Evol. Microbiol. 59, 491–497 (2009).

  4. 4.

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

  5. 5.

    Lancy, P., Dirienzo, J. M., Appelbaum, B., Rosan, B. & Holt, S. C. Corncob formation between Fusobacterium nucleatum and Streptococcus sanguis. Infect. Immun. 40, 303–309 (1983).

  6. 6.

    Guo, L., Shokeen, B., He, X., Shi, W. & Lux, R. Streptococcus mutans SpaP binds to RadD of Fusobacterium nucleatum ssp. polymorphum. Mol. Oral Microbiol. 32, 355–364 (2017).

  7. 7.

    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).

  8. 8.

    Wu, T. et al. Cellular components mediating coadherence of Candida albicans and Fusobacterium nucleatum. J. Dent. Res. 94, 1432–1438 (2015).

  9. 9.

    Manson McGuire, A. et al. Evolution of invasion in a diverse set of Fusobacterium species. MBio 5, e01864 (2014). This publication is a comparative genomic analysis of sequenced Fusobacterium species focused on potential mechanisms of molecular pathogenesis.

  10. 10.

    Zanzoni, A., Spinelli, L., Braham, S. & Brun, C. Perturbed human sub-networks by Fusobacterium nucleatum candidate virulence proteins. Microbiome 5, 89 (2017).

  11. 11.

    Tan, K. H. et al. Porphyromonas gingivalis and Treponema denticola exhibit metabolic symbioses. PLOS Pathog. 10, e1003955 (2014).

  12. 12.

    Sakanaka, A., Kuboniwa, M., Takeuchi, H., Hashino, E. & Amano, A. Arginine-ornithine antiporter ArcD controls arginine metabolism and interspecies biofilm development of Streptococcus gordonii. J. Biol. Chem. 290, 21185–21198 (2015).

  13. 13.

    Hendrickson, E. L. et al. Proteomics of Fusobacterium nucleatum within a model developing oral microbial community. Microbiologyopen 3, 729–751 (2014).

  14. 14.

    Mark Welch, J. L., Rossetti, B. J., Rieken, C. W., Dewhirst, F. E. & Borisy, G. G. Biogeography of a human oral microbiome at the micron scale. Proc. Natl Acad. Sci. USA 113, E791–E800 (2016). This publication is a technical re-exploration of the spatial organization of the microbiota in the oral cavity, revealing new layers of complexity.

  15. 15.

    Krisanaprakornkit, S. et al. Inducible expression of human beta-defensin 2 by Fusobacterium nucleatum in oral epithelial cells: multiple signaling pathways and role of commensal bacteria in innate immunity and the epithelial barrier. Infect. Immun. 68, 2907–2915 (2000).

  16. 16.

    Ahn, S.-H. et al. Transcriptome profiling analysis of senescent gingival fibroblasts in response to Fusobacterium nucleatum infection. PLOS ONE 12, e0188755 (2017).

  17. 17.

    Bhattacharyya, S. et al. FAD-I, a Fusobacterium nucleatum cell wall-associated diacylated lipoprotein that mediates human beta defensin 2 induction through Toll-like receptor-1/2 (TLR-1/2) and TLR-2/6. Infect. Immun. 84, 1446–1456 (2016).

  18. 18.

    Gallimidi, A. B. et al. Periodontal pathogens Porphyromonas gingivalis and Fusobacterium nucleatum promote tumor progression in an oral-specific chemical carcinogenesis model. Oncotarget 6, 22613–22623 (2015).

  19. 19.

    Park, S.-R. et al. Diverse Toll-like receptors mediate cytokine production by Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans in macrophages. Infect. Immun. 82, 1914–1920 (2014).

  20. 20.

    Taxman, D. J. et al. Porphyromonas gingivalis mediates inflammasome repression in polymicrobial cultures through a novel mechanism involving reduced endocytosis. J. Biol. Chem. 287, 32791–32799 (2012).

  21. 21.

    Saito, A. et al. Porphyromonas gingivalis entry into gingival epithelial cells modulated by Fusobacterium nucleatum is dependent on lipid rafts. Microb. Pathog. 53, 234–242 (2012).

  22. 22.

    Metzger, Z. et al. Synergistic pathogenicity of Porphyromonas gingivalis and Fusobacterium nucleatum in the mouse subcutaneous chamber model. J. Endod. 35, 86–94 (2009).

  23. 23.

    Swidsinski, A. et al. Acute appendicitis is characterised by local invasion with Fusobacterium nucleatum/necrophorum. Gut 60, 34–40 (2011).

  24. 24.

    Han, X. Y. et al. Fusobacterial brain abscess: a review of five cases and an analysis of possible pathogenesis. J. Neurosurg. 99, 693–700 (2003).

  25. 25.

    Gregory, S. W., Boyce, T. G., Larson, A. N., Patel, R. & Jackson, M. A. Fusobacterium nucleatum osteomyelitis in 3 previously healthy children: a case series and review of the literature. J. Pediatr. Infect. Dis. Soc. 4, e155–e159 (2015).

  26. 26.

    Truant, A. L., Menge, S., Milliorn, K., Lairscey, R. & Kelly, M. T. Fusobacterium nucleatum pericarditis. J. Clin. Microbiol. 17, 349–351 (1983).

  27. 27.

    Altshuler, G. & Hyde, S. Clinicopathologic considerations of fusobacteria chorioamnionitis. Acta Obstet. Gynecol. Scand. 67, 513–517 (1988).

  28. 28.

    Tjalsma, H., Boleij, A., Marchesi, J. R. & Dutilh, B. E. A bacterial driver-passenger model for colorectal cancer: beyond the usual suspects. Nat. Rev. Microbiol. 10, 575–582 (2012).

  29. 29.

    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).

  30. 30.

    Ikegami, A., Chung, P. & Han, Y. W. Complementation of the fadA mutation in Fusobacterium nucleatum demonstrates that the surface-exposed adhesin promotes cellular invasion and placental colonization. Infect. Immun. 77, 3075–3079 (2009).

  31. 31.

    Han, Y. W. et al. Interactions between periodontal bacteria and human oral epithelial cells: Fusobacterium nucleatum adheres to and invades epithelial cells. Infect. Immun. 68, 3140–3146 (2000).

  32. 32.

    Kinder Haake, S. & Lindemann, R. A. Fusobacterium nucleatum T18 aggregates human mononuclear cells and inhibits their PHA-stimulated proliferation. J. Periodontol. 68, 39–44 (1997).

  33. 33.

    Gursoy, U. K., Könönen, E. & Uitto, V.-J. Intracellular replication of fusobacteria requires new actin filament formation of epithelial cells. APMIS 116, 1063–1070 (2008).

  34. 34.

    Weiss, E. I. et al. Attachment of Fusobacterium nucleatum PK1594 to mammalian cells and its coaggregation with periodontopathogenic bacteria are mediated by the same galactose-binding adhesin. Oral Microbiol. Immunol. 15, 371–377 (2000).

  35. 35.

    Han, Y. W. et al. Fusobacterium nucleatum induces premature and term stillbirths in pregnant mice: implication of oral bacteria in preterm birth. Infect. Immun. 72, 2272–2279 (2004). This publication provides evidence in a preclinical model to support the association of fusobacteria with adverse pregnancy outcomes in humans.

  36. 36.

    Xu, M. et al. FadA from Fusobacterium nucleatum utilizes both secreted and nonsecreted forms for functional oligomerization for attachment and invasion of host cells. J. Biol. Chem. 282, 25000–25009 (2007).

  37. 37.

    Fardini, Y. et al. Fusobacterium nucleatum adhesin FadA binds vascular endothelial cadherin and alters endothelial integrity. Mol. Microbiol. 82, 1468–1480 (2011).

  38. 38.

    Aagaard, K. et al. The placenta harbors a unique microbiome. Sci. Transl Med. 6, 237ra65 (2014).

  39. 39.

    Hatakeyama, M. Helicobacter pylori CagA and gastric cancer: a paradigm for hit-and-run carcinogenesis. Cell Host Microbe 15, 306–316 (2014).

  40. 40.

    Kostic, A. D. et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 22, 292–298 (2012).

  41. 41.

    Castellarin, M. et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 22, 299–306 (2012).

  42. 42.

    Gevers, D. et al. The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe 15, 382–392 (2014).

  43. 43.

    Pascal, V. et al. A microbial signature for Crohn’s disease. Gut 66, 813–822 (2017).

  44. 44.

    McCoy, A. N. et al. Fusobacterium is associated with colorectal adenomas. PLOS ONE 8, e53653 (2013).

  45. 45.

    Gur, C. et al. Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. Immunity 42, 344–355 (2015).

  46. 46.

    Bullman, S. et al. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science 358, 1443–1448 (2017).

  47. 47.

    Feng, Q. et al. Gut microbiome development along the colorectal adenoma-carcinoma sequence. Nat. Commun. 6, 6528 (2015).

  48. 48.

    Yu, J. et al. Invasive Fusobacterium nucleatum may play a role in the carcinogenesis of proximal colon cancer through the serrated neoplasia pathway. Int. J. Cancer 139, 1318–1326 (2016).

  49. 49.

    Li, Y.-Y. et al. Association of Fusobacterium nucleatum infection with colorectal cancer in Chinese patients. World J. Gastroenterol. 22, 3227–3233 (2016).

  50. 50.

    Al-Hebshi, N. N. et al. Inflammatory bacteriome featuring Fusobacterium nucleatum and Pseudomonas aeruginosa identified in association with oral squamous cell carcinoma. Sci. Rep. 7, 1834 (2017).

  51. 51.

    Zhao, H. et al. Variations in oral microbiota associated with oral cancer. Sci. Rep. 7, 11773 (2017).

  52. 52.

    Audirac-Chalifour, A. et al. Cervical microbiome and cytokine profile at various stages of cervical cancer: a pilot study. PLOS ONE 11, e0153274 (2016).

  53. 53.

    Hsieh, Y.-Y. et al. Increased abundance of Clostridium and Fusobacterium in gastric microbiota of patients with gastric cancer in Taiwan. Sci. Rep. 8, 158 (2018).

  54. 54.

    Yamamura, K. et al. Human microbiome Fusobacterium nucleatum in esophageal cancer tissue is associated with prognosis. Clin. Cancer Res. 22, 5574–5581 (2016).

  55. 55.

    Warren, R. L. et al. Co-occurrence of anaerobic bacteria in colorectal carcinomas. Microbiome 1, 16 (2013).

  56. 56.

    Dejea, C. M. et al. Microbiota organization is a distinct feature of proximal colorectal cancers. Proc. Natl Acad. Sci. USA 111, 18321–18326 (2014).

  57. 57.

    Guo, S. et al. A simple and novel fecal biomarker for colorectal cancer: ratio of Fusobacterium nucleatum to probiotics populations, based on their antagonistic effect. Clin. Chem. 64, 1327–1337 (2018).

  58. 58.

    Mima, K. et al. Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis. Gut 65, 1973–1980 (2015). This molecular epidemiology study highlights the association of tumoural fusobacterial levels with worse prognosis in colorectal cancer.

  59. 59.

    Yu, T. et al. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell 170, 548–563 (2017). This work explores the links between fusobacteria, colon cancer and autophagy, suggesting that fusobacteria may confer chemoresistance in colon cancers.

  60. 60.

    Tahara, T. et al. Fusobacterium in colonic flora and molecular features of colorectal carcinoma. Cancer Res. 74, 1311–1318 (2014).

  61. 61.

    Ito, M. et al. Association of Fusobacterium nucleatum with clinical and molecular features in colorectal serrated pathway. Int. J. Cancer 137, 1258–1268 (2015).

  62. 62.

    Mima, K. et al. Fusobacterium nucleatum in colorectal carcinoma tissue according to tumor location. Clin. Transl Gastroenterol. 7, e200 (2016).

  63. 63.

    Mima, K. et al. Fusobacterium nucleatum and T cells in colorectal carcinoma. JAMA Oncol. 1, 653–661 (2015).

  64. 64.

    Mehta, R. S. et al. Association of dietary patterns with risk of colorectal cancer subtypes classified by Fusobacterium nucleatum in tumor tissue. JAMA Oncol. 3, 921–927 (2017).

  65. 65.

    Liu, L. et al. Diets that promote colon inflammation associate with risk of colorectal carcinomas that contain Fusobacterium nucleatum. Clin. Gastroenterol. Hepatol. 16, 1622–1631 (2018).

  66. 66.

    Komiya, Y. et al. Patients with colorectal cancer have identical strains of Fusobacterium nucleatum in their colorectal cancer and oral cavity. Gut https://doi.org/10.1136/gutjnl-2018-316661 (2018).

  67. 67.

    Yang, G. Y. & Shamsuddin, A. M. Gal-GalNAc: a biomarker of colon carcinogenesis. Histol. Histopathol. 11, 801–806 (1996).

  68. 68.

    Coppenhagen-Glazer, S. et al. Fap2 of Fusobacterium nucleatum is a galactose-inhibitable adhesin involved in coaggregation, cell adhesion, and preterm birth. Infect. Immun. 83, 1104–1113 (2015).

  69. 69.

    Abed, J. et al. Fap2 mediates Fusobacterium nucleatum colorectal adenocarcinoma enrichment by binding to tumor-expressed Gal-GalNAc. Cell Host Microbe 20, 215–225 (2016).

  70. 70.

    Carroll, G. C. & Sebor, R. J. Dental flossing and its relationship to transient bacteremia. J. Periodontol. 51, 691–692 (1980).

  71. 71.

    Lockhart, P. B. et al. Bacteremia associated with toothbrushing and dental extraction. Circulation 117, 3118–3125 (2008).

  72. 72.

    Su, L. K. et al. Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science 256, 668–670 (1992).

  73. 73.

    Moser, A. R., Pitot, H. C. & Dove, W. F. A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science 247, 322–324 (1990).

  74. 74.

    Kostic, A. D. et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 14, 207–215 (2013).

  75. 75.

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

  76. 76.

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

  77. 77.

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

  78. 78.

    Sanders, B. E., Umana, A., Lemkul, J. A. & Slade, D. J. FusoPortal: an interactive repository of hybrid MinION-sequenced fusobacterium genomes improves gene identification and characterization. mSphere 3, 284 (2018).

  79. 79.

    Rubinstein, M. R. et al. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin. Cell Host Microbe 14, 195–206 (2013). This publication and reference 74 are seminal papers supporting that fusobacteria potentiate colonic tumorigenesis.

  80. 80.

    White, B. D., Chien, A. J. & Dawson, D. W. Dysregulation of Wnt/β-catenin signaling in gastrointestinal cancers. Gastroenterology 142, 219–232 (2012).

  81. 81.

    Dougall, W. C., Kurtulus, S., Smyth, M. J. & Anderson, A. C. TIGIT and CD96: new checkpoint receptor targets for cancer immunotherapy. Immunol. Rev. 276, 112–120 (2017).

  82. 82.

    Wang, H.-F. et al. Evaluation of antibody level against Fusobacterium nucleatum in the serological diagnosis of colorectal cancer. Sci. Rep. 6, 33440 (2016).

  83. 83.

    Dejea, C. M. et al. Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. Science 359, 592–597 (2018).

  84. 84.

    Wu, Y. et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis in mice via a Toll-like receptor 4/p21-activated kinase 1 cascade. Dig. Dis. Sci. 63, 1210–1218 (2018).

  85. 85.

    Routy, B. et al. The gut microbiota influences anticancer immunosurveillance and general health. Nat. Rev. Clin. Oncol. 15, 382–396 (2018).

  86. 86.

    Bennett, J. E., Dolin, R. & Blaser, M. J. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Disease (Elsevier Health Sciences, 2014).

  87. 87.

    Liu, P.-F., Huang, I.-F., Shu, C.-W. & Huang, C.-M. Halitosis vaccines targeting FomA, a biofilm-bridging protein of fusobacteria nucleatum. Curr. Mol. Med. 13, 1358–1367 (2013).

  88. 88.

    Guo, S.-H. et al. Immunization with alkyl hydroperoxide reductase subunit C reduces Fusobacterium nucleatum load in the intestinal tract. Sci. Rep. 7, 10566 (2017).

  89. 89.

    Petrof, E. O., Claud, E. C., Gloor, G. B. & Allen-Vercoe, E. Microbial ecosystems therapeutics: a new paradigm in medicine? Benef. Microbes 4, 53–65 (2013).

  90. 90.

    Blaser, M. J. Helicobacter pylori and esophageal disease: wake-up call? Gastroenterology 139, 1819–1822 (2010).

  91. 91.

    Blaser, M. J. Helicobacter pylori eradication and its implications for the future. Aliment. Pharmacol. Ther. 11 (Suppl. 1), 103–107 (1997).

  92. 92.

    O’Keefe, S. J. D. et al. Fat, fibre and cancer risk in African Americans and rural Africans. Nat. Commun. 6, 6342 (2015).

  93. 93.

    Duncan, S. H., Hold, G. L., Harmsen, H. J. M., Stewart, C. S. & Flint, H. J. Growth requirements and fermentation products of Fusobacterium prausnitzii, and a proposal to reclassify it as Faecalibacterium prausnitzii gen. nov., comb. nov. Int. J. Syst. Evol. Microbiol. 52, 2141–2146 (2002).

  94. 94.

    Jalava, J. & Eerola, E. Phylogenetic analysis of Fusobacterium alocis and Fusobacterium sulci based on 16S rRNA gene sequences: proposal of Filifactor alocis (Cato, Moore and Moore) comb. nov. and Eubacterium sulci (Cato, Moore and Moore) comb. nov. Int. J. Syst. Bacteriol. 49, 1375–1379 (1999).

  95. 95.

    Todd, S. M., Settlage, R. E., Lahmers, K. K. & Slade, D. J. Fusobacterium genomics using MinION and illumina sequencing enables genome completion and correction. mSphere 3, 284 (2018).

  96. 96.

    Gupta, R. S. & Sethi, M. Phylogeny and molecular signatures for the phylum Fusobacteria and its distinct subclades. Anaerobe 28, 182–198 (2014).

  97. 97.

    Nie, S. et al. Fusobacterium nucleatum subspecies identification by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J. Clin. Microbiol. 53, 1399–1402 (2015).

  98. 98.

    Kook, J.-K. et al. Genome-based reclassification of Fusobacterium nucleatum subspecies at the species level. Curr. Microbiol. 74, 1137–1147 (2017).

  99. 99.

    Repass, J., Maherali, N. & Owen, K. Reproducibility project: cancer biology. Registered report: Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. eL ife 5, 427 (2016).

  100. 100.

    Repass, J. et al. Replication study: Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. eLife 7, e64900 (2018).

  101. 101.

    Errington, T. M. et al. An open investigation of the reproducibility of cancer biology research. eLife 3, 5773 (2014).

  102. 102.

    Boleij, A. et al. The Bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients. Clin. Infect. Dis. 60, 208–215 (2015).

  103. 103.

    Arthur, J. C. et al. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 338, 120–123 (2012).

  104. 104.

    Kinder-Haake, S., Yoder, S. & Hunt Gerardo, S. Efficient gene transfer and targeted mutagenesis in Fusobacterium nucleatum. Plasmid 55, 27–38 (2006). This foundational paper establishes techniques for genetic manipulation of fusobacteria.

  105. 105.

    Nakagaki, H. et al. Fusobacterium nucleatum envelope protein FomA is immunogenic and binds to the salivary statherin-derived peptide. Infect. Immun. 78, 1185–1192 (2010).

  106. 106.

    Han, Y. W. et al. Identification and characterization of a novel adhesin unique to oral fusobacteria. J. Bacteriol. 187, 5330–5340 (2005).

  107. 107.

    Casasanta, M. A. et al. A chemical and biological toolbox for Type Vd secretion: characterization of the phospholipase A1 autotransporter FplA from Fusobacterium nucleatum. J. Biol. Chem. 292, 20240–20254 (2017).

  108. 108.

    Ma, L., Ding, Q., Feng, X. & Li, F. The protective effect of recombinant FomA-expressing Lactobacillus acidophilus against periodontal infection. Inflammation 36, 1160–1170 (2013).

  109. 109.

    Wu, C. et al. Forward genetic dissection of biofilm development by Fusobacterium nucleatum: novel functions of cell division proteins FtsX and EnvC. MBio 9, 101 (2018). This recent publication expands the fusobacterial genetic toolkit.

  110. 110.

    Han, Y. W., Ikegami, A., Chung, P., Zhang, L. & Deng, C. X. Sonoporation is an efficient tool for intracellular fluorescent dextran delivery and one-step double-crossover mutant construction in Fusobacterium nucleatum. Appl. Environ. Microbiol. 73, 3677–3683 (2007).

  111. 111.

    Yang, Y. et al. 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, 851–866 (2017).

  112. 112.

    Kolenbrander, P. E., Andersen, R. N. & Moore, L. V. Coaggregation of Fusobacterium nucleatum, Selenomonas flueggei, Selenomonas infelix, Selenomonas noxia, and Selenomonas sputigena with strains from 11 genera of oral bacteria. Infect. Immun. 57, 3194–3203 (1989).

  113. 113.

    Tomkovich, S. et al. Locoregional effects of microbiota in a preclinical model of colon carcinogenesis. Cancer Res. 77, 2620–2632 (2017).

  114. 114.

    Kokes, M. et al. Integrating chemical mutagenesis and whole-genome sequencing as a platform for forward and reverse genetic analysis of Chlamydia. Cell Host Microbe 17, 716–725 (2015).

  115. 115.

    Zarkavelis, G. et al. Current and future biomarkers in colorectal cancer. Ann. Gastroenterol. 30, 613–621 (2017).

  116. 116.

    Imperiale, T. F., Ransohoff, D. F. & Itzkowitz, S. H. Multitarget stool DNA testing for colorectal-cancer screening. N. Engl. J. Med. 371, 187–188 (2014).

  117. 117.

    Nakatsu, G. et al. Gut mucosal microbiome across stages of colorectal carcinogenesis. Nat. Commun. 6, 8727 (2015).

  118. 118.

    Peng, B.-J. et al. Diagnostic performance of intestinal Fusobacterium nucleatum in colorectal cancer: a meta-analysis. Chin. Med. J. 131, 1349–1356 (2018).

  119. 119.

    Huang, Q., Peng, Y. & Xie, F. Fecal fusobacterium nucleatum for detecting colorectal cancer: a systematic review and meta-analysis. Int. J. Biol. Markers https://doi.org/10.1177/1724600818781301 (2018).

  120. 120.

    Sze, M. A. & Schloss, P. D. Leveraging existing 16S rRNA gene surveys to identify reproducible biomarkers in individuals with colorectal tumors. MBio 9, 7 (2018).

  121. 121.

    Kaplan, A. et al. Characterization of aid1, a novel gene involved in Fusobacterium nucleatum interspecies interactions. Microb. Ecol. 68, 379–387 (2014).

  122. 122.

    Lima, B. P., Shi, W. & Lux, R. Identification and characterization of a novel Fusobacterium nucleatum adhesin involved in physical interaction and biofilm formation with Streptococcus gordonii. Microbiologyopen 6, e00444 (2017).

  123. 123.

    Park, J., Shokeen, B., Haake, S. K. & Lux, R. Characterization of Fusobacterium nucleatum ATCC 23726 adhesins involved in strain-specific attachment to Porphyromonas gingivalis. Int. J. Oral Sci. 8, 138–144 (2016).

  124. 124.

    Kinder, S. A. & Holt, S. C. Localization of the Fusobacterium nucleatum T18 adhesin activity mediating coaggregation with Porphyromonas gingivalis T22. J. Bacteriol. 175, 840–850 (1993).

  125. 125.

    Liu, P.-F. et al. Vaccination targeting surface FomA of Fusobacterium nucleatum against bacterial co-aggregation: implication for treatment of periodontal infection and halitosis. Vaccine 28, 3496–3505 (2010).

  126. 126.

    Bolstad, A. I., Jensen, H. B. & Bakken, V. Taxonomy, biology, and periodontal aspects of Fusobacterium nucleatum. Clin. Microbiol. Rev. 9, 55–71 (1996).

  127. 127.

    Riordan, T. Human infection with Fusobacterium necrophorum (Necrobacillosis), with a focus on Lemierre’s syndrome. Clin. Microbiol. Rev. 20, 622–659 (2007).

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This work is supported by US National Institutes of Health (NIH) grant R01CA154426. C.A.B. is the Dennis and Marsha Dammerman fellow of the Damon Runyon Cancer Research Foundation (DRG-2205-14).

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Both authors researched data for the article, made substantial contributions to discussions of the content, wrote the article and reviewed and edited the manuscript before submission.

Correspondence to Wendy S. Garrett.

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Competing interests

W.S.G. serves on the Scientific Advisory Boards of Evelo Biosciences, Kintai Therapeutics and uBiome. W.S.G. is a consultant for BioMx and has been a consultant for Janssen, Pfizer and Merck. W.S.G. is a senior editor at eLife, which publishes the ‘Reproducibility Project: Cancer Biology’ experimental designs and methods as registered reports and results as replication studies.

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Supplementary Information


Combinatorial labelling and spectral imaging–fluorescence in situ hybridization

(CLASI-FISH). This technique enables detection of ten to several hundred distinct microbial taxa by using combinations of fluorophores coupled to different oligonucleotide probes that target unique regions of the 16S ribosomal RNA (rRNA) gene.


Infectious or non-infectious inflammation of the bone.


Infectious or non-infectious inflammation of the sac-like tissue that surrounds the heart.


Infectious or non-infectious inflammation of the chorion and amnion (the fetal membranes) and the amniotic fluid, which can occur before or during labour.

Lemierre syndrome

Infectious thrombophlebitis of the internal jugular vein, which is often caused by F. necrophorum. It can occur in the setting of a fusobacterial throat infection with peritonsillar abscess formation, but in the modern antibiotic era it remains fairly rare. The syndrome is named after Andrew Lemierre, who published a case report in the 1930s that identified throat infections as the cause of several anaerobic sepsis cases.

CpG island methylator phenotype

(CIMP). A state of epigenetic instability in which promoter CpG island sites become hypermethylated, which results in turning off of genes, including tumour suppressor genes.

Microsatellite instability

A condition in which impaired DNA mismatch repair leads to genetic hypermutation. Colorectal tumours can be described as microsatellite instable-high (MSI-high) or microsatellite stable (MSS).

Familial adenomatous polyposis

A genetic disorder that is caused by mutation of the APC gene and results in numerous tumours of the large bowel. Classically, these colon tumours form during the teenage years and the number of tumours increases with age, but there are also attenuated variants.

Colorectal adenomas

Non-malignant tumours occurring in the colon and rectum that can develop into cancer.

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Brennan, C.A., Garrett, W.S. Fusobacterium nucleatum — symbiont, opportunist and oncobacterium. Nat Rev Microbiol 17, 156–166 (2019) doi:10.1038/s41579-018-0129-6

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