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Bacteria in cancer initiation, promotion and progression

Nature Reviews Cancer volume 23, pages 600–618 (2023)Cite this article

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Abstract

Cancer cells originate from a series of acquired genetic mutations that can drive their uncontrolled cell proliferation and immune evasion. Environmental factors, including the microorganisms that colonize the human body, can shift the metabolism, growth pattern and function of neoplastic cells and shape the tumour microenvironment. Dysbiosis of the gut microbiome is now recognized as a hallmark of cancer by the scientific community. However, only a few microorganisms have been identified that directly initiate tumorigenesis or skew the immune system to generate a tumour-permissive milieu. Over the past two decades, research on the human microbiome and its functionalities within and across individuals has revealed microbiota-focused strategies for health and disease. Here, we review the evolving understanding of the mechanisms by which the microbiota acts in cancer initiation, promotion and progression. We explore the roles of bacteria in gastrointestinal tract malignancies and cancers of the lung, breast and prostate. Finally, we discuss the promises and limitations of targeting or harnessing bacteria in personalized cancer prevention, diagnostics and treatment.

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Fig. 1: Mechanisms of bacteria-associated tumorigenesis in gastrointestinal organs.
Fig. 2: Bacteria-associated tumorigenesis in the pancreas and lung.
Fig. 3: Microbiota tumour-associated features in breast and prostate cancer.

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References

  1. Poore, G. D. et al. Microbiome analyses of blood and tissues suggest cancer diagnostic approach. Nature 579, 567–574 (2020). This study shows that the tumour microbiome composition and the immune system play a crucial prognosis role in PDAC where higher alpha-diversity and specific microbiome signatures are linked to long-term PDAC survival.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Nejman, D. et al. The human tumor microbiome is composed of tumor type-specific intracellular bacteria. Science 368, 973–980 (2020). This study analyses the intra-tumoural microbiome of 1,526 tumours across seven cancer types, revealing that each tumour type has a distinct microbiome composition as well as correlations between the intra-tumoural bacteria, their predicted functions, tumour types and subtypes, factors such as patients’ smoking status and response to immunotherapy.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kolodziejczyk, A. A., Zheng, D. & Elinav, E. Diet–microbiota interactions and personalized nutrition. Nat. Rev. Microbiol. 17, 742–753 (2019).

    Article  CAS  PubMed  Google Scholar 

  4. Shreiner, A. B., Kao, J. Y. & Young, V. B. The gut microbiome in health and in disease. Curr. Opin. Gastroenterol. 31, 69–75 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Cao, Y. et al. Long-term use of antibiotics and risk of colorectal adenoma. Gut 67, 672–678 (2018).

    CAS  PubMed  Google Scholar 

  6. Velicer, C. M. et al. Antibiotic use in relation to the risk of breast cancer. J. Am. Med. Assoc. 291, 827–835 (2004).

    Article  CAS  Google Scholar 

  7. Yonekura, S. et al. Cancer induces a stress ileopathy depending on β-adrenergic receptors and promoting dysbiosis that contributes to carcinogenesis. Cancer Discov. 12, 1128–1151 (2022).

    Article  CAS  PubMed  Google Scholar 

  8. Plummer, M. et al. Global burden of cancers attributable to infections in 2012: a synthetic analysis. Lancet Glob. Health 4, e609–e616 (2016).

    Article  PubMed  Google Scholar 

  9. de Martel, C., Georges, D., Bray, F., Ferlay, J. & Clifford, G. M. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob. Health 8, e180–e190 (2020).

    Article  PubMed  Google Scholar 

  10. Garrett, W. S. Cancer and the microbiota. Science 348, 80–86 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hanahan, D. Hallmarks of cancer: new dimensions. Cancer Discov. 12, 31–46 (2022).

    Article  CAS  PubMed  Google Scholar 

  12. Parsonnet, J. et al. Helicobacter pylori infection and gastric lymphoma. N. Engl. J. Med. 330, 1267–1271 (1994).

    Article  CAS  PubMed  Google Scholar 

  13. Geis, A. L. et al. Regulatory T-cell response to enterotoxigenic Bacteroides fragilis colonization triggers IL17-dependent colon carcinogenesis. Cancer Discov. 5, 1098–1109 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

  15. Kostic, A. D. et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 14, 207–215 (2013). This paper demonstrates that F. nucleatum plays a significant role in promoting intestinal tumorigenesis in humans and mice by driving a pro-inflammatory tumour milieu and MDSC infiltration.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sepe, L. P. et al. Genotoxic effect of Salmonella paratyphi A infection on human primary gallbladder cells. mBio 11, e01911–e01920 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Parhi, L. et al. Breast cancer colonization by Fusobacterium nucleatum accelerates tumor growth and metastatic progression. Nat. Commun. 11, 3259 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Riquelme, E. et al. Tumor microbiome diversity and composition influence pancreatic cancer outcomes. Cell 178, 795–806.e12 (2019). This study identifies a microbiome signature predictive of long-term survival in patients with pancreatic cancer and demonstrates that modulating the tumour microbiome through faecal microbiota transplantation can affect tumour growth and immune infiltration.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Viaud, S. et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 342, 971–976 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Iida, N. et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 342, 967–970 (2013). Together with Viaud et al. (2013), this study uncovers for the first time the significant involvement of microbiota in regulating the response to immunotherapy and chemotherapy, establishing that a healthy gut microbiota activates tumour-associated myeloid cells to produce pro-inflammatory cytokines and ROS.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Vétizou, M. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079–1084 (2015). This study uncovers the role of the microbiome in response to the immune checkpoint blockade anti-CTLA4, finding that specific gut microbiota members, such as B. fragilis, modulate the anticancer immune response induced by anti-CTLA4 therapy in both mice and humans.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Gopalakrishnan, V. et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 359, 97–103 (2018).

    Article  CAS  PubMed  Google Scholar 

  23. Routy, B. et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359, 91–97 (2018).

    Article  CAS  PubMed  Google Scholar 

  24. Matson, V. et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 359, 104–108 (2018). Together with Gopalakrishnan et al. (2018) and Routy et al. (Science, 2018), this study discovers that faecal microbiota transplantation from patients with cancer who responded to immune checkpoint blockade can restore the antitumour effects of PD-1 blockade in patients who are non-responders.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Stein-Thoeringer, C. K. et al. A non-antibiotic-disrupted gut microbiome is associated with clinical responses to CD19–CAR-T cell cancer immunotherapy. Nat. Med. 29, 906–916 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Spencer, C. N. et al. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science 374, 1632–1640 (2021). This study finds that higher dietary fibre intake is associated with improved response to immune checkpoint blockade treatment in patients with melanoma, with preclinical models showing impaired treatment response in mice receiving a low-fibre diet.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 486, 207–214 (2012).

    Article  Google Scholar 

  29. Matson, V. & Gajewski, T. F. Dietary modulation of the gut microbiome as an immunoregulatory intervention. Cancer Cell 40, 246–248 (2022).

    Article  CAS  PubMed  Google Scholar 

  30. Walboomers, J. M. et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J. Pathol. 189, 12–19 (1999).

    Article  CAS  PubMed  Google Scholar 

  31. Aykut, B. et al. The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL. Nature 574, 264–267 (2019). This study describes how fungi translocation from the gut to the pancreas promotes oncogenesis, uncovering the essential role of the mannose-binding lectin-complement cascade pathway activation in driving pancreatic cancer progression.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Dohlman, A. B. et al. A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors. Cell 185, 3807–3822.e12 (2022).

    Article  CAS  PubMed  Google Scholar 

  33. Cho, I. & Blaser, M. J. The human microbiome: at the interface of health and disease. Nat. Rev. Genet. 13, 260–270 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Carding, S., Verbeke, K., Vipond, D. T., Corfe, B. M. & Owen, L. J. Dysbiosis of the gut microbiota in disease. Microb. Ecol. Health Dis. 26, 26191 (2015).

    PubMed  Google Scholar 

  35. Clay, S. L., Fonseca-Pereira, D. & Garrett, W. S. Colorectal cancer: the facts in the case of the microbiota. J. Clin. Invest. 132, e155101 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Warren, J. R. & Marshall, B. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet Lond. Engl. 1, 1273–1275 (1983).

    CAS  Google Scholar 

  37. Wang, F., Meng, W., Wang, B. & Qiao, L. Helicobacter pylori-induced gastric inflammation and gastric cancer. Cancer Lett. 345, 196–202 (2014).

    Article  CAS  PubMed  Google Scholar 

  38. Van Rossum, T., Ferretti, P., Maistrenko, O. M. & Bork, P. Diversity within species: interpreting strains in microbiomes. Nat. Rev. Microbiol. 18, 491–506 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Cover, T. L., Lacy, D. B. & Ohi, M. D. The Helicobacter pylori Cag type IV secretion system. Trends Microbiol. 28, 682–695 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Parsonnet, J. Clinician-discoverers — Marshall, Warren, and H. pylori. N. Engl. J. Med. 353, 2421–2423 (2005).

    Article  CAS  PubMed  Google Scholar 

  41. Howden, C. W. & Hunt, R. H. Relationship between gastric secretion and infection. Gut 28, 96–107 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Mobley, H. L., Cortesia, M. J., Rosenthal, L. E. & Jones, B. D. Characterization of urease from Campylobacter pylori. J. Clin. Microbiol. 26, 831–836 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Fallone, C. A. et al. The Toronto consensus for the treatment of Helicobacter pylori infection in adults. Gastroenterology 151, 51–69.e14 (2016).

    Article  PubMed  Google Scholar 

  44. Cheung, K. S. et al. Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study. Gut 67, 28–35 (2018).

    Article  CAS  PubMed  Google Scholar 

  45. Nehra, A. K., Alexander, J. A., Loftus, C. G. & Nehra, V. Proton pump inhibitors: review of emerging concerns. Mayo Clin. Proc. 93, 240–246 (2018).

    Article  CAS  PubMed  Google Scholar 

  46. Yang, Y.-X., Lewis, J. D., Epstein, S. & Metz, D. C. Long-term proton pump inhibitor therapy and risk of hip fracture. J. Am. Med. Assoc. 296, 2947–2953 (2006).

    Article  CAS  Google Scholar 

  47. Janarthanan, S., Ditah, I., Adler, D. G. & Ehrinpreis, M. N. Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis. Am. J. Gastroenterol. 107, 1001–1010 (2012).

    Article  CAS  PubMed  Google Scholar 

  48. Laheij, R. J. F. et al. Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. J. Am. Med. Assoc. 292, 1955–1960 (2004).

    Article  CAS  Google Scholar 

  49. Sherwood, M. W. et al. Individual proton pump inhibitors and outcomes in patients with coronary artery disease on dual antiplatelet therapy: a systematic review. J. Am. Heart Assoc. 4, e002245 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Königer, V. et al. Helicobacter pylori exploits human CEACAMs via HopQ for adherence and translocation of CagA. Nat. Microbiol. 2, 16188 (2016). This study identifies HopQ as the adhesin of H. pylori enabling translocation of the pathogenicity factor into host cells, and thus contributing to H. pylori-induced peptic ulcer disease and gastric adenocarcinoma.

    Article  PubMed  Google Scholar 

  51. Maeda, S. et al. Distinct mechanism of Helicobacter pylori-mediated NF-κB activation between gastric cancer cells and monocytic cells. J. Biol. Chem. 276, 44856–44864 (2001).

    Article  CAS  PubMed  Google Scholar 

  52. Viala, J. et al. Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nat. Immunol. 5, 1166–1174 (2004).

    Article  CAS  PubMed  Google Scholar 

  53. Suzuki, N. et al. Mutual reinforcement of inflammation and carcinogenesis by the Helicobacter pylori CagA oncoprotein. Sci. Rep. 5, 10024 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Zavros, Y. & Merchant, J. L. The immune microenvironment in gastric adenocarcinoma. Nat. Rev. Gastroenterol. Hepatol. 19, 451–467 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Stolte, M. et al. Helicobacter and gastric MALT lymphoma. Gut 50 (Suppl. 3), III19–III24 (2002).

    PubMed  PubMed Central  Google Scholar 

  56. Lin, W.-C. et al. Translocation of Helicobacter pylori CagA into human B lymphocytes, the origin of mucosa-associated lymphoid tissue lymphoma. Cancer Res. 70, 5740–5748 (2010).

    Article  CAS  PubMed  Google Scholar 

  57. Ruskoné-Fourmestraux, A. et al. EGILS consensus report. Gastric extranodal marginal zone B-cell lymphoma of MALT. Gut 60, 747–758 (2011).

    Article  PubMed  Google Scholar 

  58. Park, H. S., Kim, Y. J., Yang, W. I., Suh, C. O. & Lee, Y. C. Treatment outcome of localized Helicobacter pylori-negative low-grade gastric MALT lymphoma. World J. Gastroenterol. 16, 2158–2162 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Zullo, A. et al. Eradication therapy in Helicobacter pylori-negative, gastric low-grade mucosa-associated lymphoid tissue lymphoma patients: a systematic review. J. Clin. Gastroenterol. 47, 824–827 (2013).

    Article  PubMed  Google Scholar 

  60. Islami, F. & Kamangar, F. Helicobacter pylori and esophageal cancer risk: a meta-analysis. Cancer Prev. Res. 1, 329–338 (2008).

    Article  CAS  Google Scholar 

  61. Holleczek, B., Schöttker, B. & Brenner, H. Helicobacter pylori infection, chronic atrophic gastritis and risk of stomach and esophagus cancer: results from the prospective population-based ESTHER cohort study. Int. J. Cancer 146, 2773–2783 (2020).

    Article  CAS  PubMed  Google Scholar 

  62. Chiba, N. cagA-seropositive strains of Helicobacter pylori increase the risk for gastric cancer more than the presence of H pylori alone. Can. J. Gastroenterol. J. Can. Gastroenterol. 18, 341–343 (2004).

    Article  Google Scholar 

  63. Ding, S.-Z. Global whole family based — Helicobacter pylori eradication strategy to prevent its related diseases and gastric cancer. World J. Gastroenterol. 26, 995–1004 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  64. Argueta, E. A. & Moss, S. F. The prevention of gastric cancer by Helicobacter pylori eradication. Curr. Opin. Gastroenterol. 37, 625–630 (2021).

    Article  CAS  PubMed  Google Scholar 

  65. Roa, J. C. et al. Gallbladder cancer. Nat. Rev. Dis. Prim. 8, 69 (2022).

    Article  PubMed  Google Scholar 

  66. Randi, G., Franceschi, S. & La Vecchia, C. Gallbladder cancer worldwide: geographical distribution and risk factors. Int. J. Cancer 118, 1591–1602 (2006).

    Article  CAS  PubMed  Google Scholar 

  67. Shukla, R. et al. Roles of Salmonella typhi and Salmonella paratyphi in gallbladder cancer development. Asian Pac. J. Cancer Prev. 22, 509–516 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Di Domenico, E. G., Cavallo, I., Pontone, M., Toma, L. & Ensoli, F. Biofilm producing Salmonella Typhi: chronic colonization and development of gallbladder cancer. Int. J. Mol. Sci. 18, E1887 (2017).

    Article  Google Scholar 

  69. Liu, X., Lu, R., Wu, S. & Sun, J. Salmonella regulation of intestinal stem cells through the Wnt/β-catenin pathway. FEBS Lett. 584, 911–916 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Song, J., Gao, X. & Galán, J. E. Structure and function of the Salmonella Typhi chimaeric A2B5 typhoid toxin. Nature 499, 350–354 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Spanò, S., Ugalde, J. E. & Galán, J. E. Delivery of a Salmonella Typhi exotoxin from a host intracellular compartment. Cell Host Microbe 3, 30–38 (2008).

    Article  PubMed  Google Scholar 

  72. Haghjoo, E. & Galán, J. E. Salmonella typhi encodes a functional cytolethal distending toxin that is delivered into host cells by a bacterial-internalization pathway. Proc. Natl Acad. Sci. USA 101, 4614–4619 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. McCann, N., Scott, P., Parry, C. M. & Brown, M. Antimicrobial agents for the treatment of enteric fever chronic carriage: a systematic review. PLoS ONE 17, e0272043 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Sekirov, I., Russell, S. L., Antunes, L. C. M. & Finlay, B. B. Gut microbiota in health and disease. Physiol. Rev. 90, 859–904 (2010).

    Article  CAS  PubMed  Google Scholar 

  75. Zheng, D., Liwinski, T. & Elinav, E. Interaction between microbiota and immunity in health and disease. Cell Res. 30, 492–506 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  76. Pleguezuelos-Manzano, C. et al. Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli. Nature 580, 269–273 (2020). This study finds that exposing human intestinal organoids to genotoxic pks+ E. coli results in a distinct mutational signature that was also found in a subset of human CRC genomes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. 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). The study investigates the role of ETBF in promoting colon tumour formation and that ETBF triggers colitis and strongly induces colonic tumours in mice by activating the Stat3 and TH17 cell-dependent immune pathway, providing new insights into human colon carcinogenesis.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. 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 

  83. Drewes, J. L. et al. Human colon cancer-derived Clostridioides difficile strains drive colonic tumorigenesis in mice. Cancer Discov. 12, 1873–1885 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Alcock, F. & Palmer, T. Activation of a bacterial killing machine. PLoS Genet. 17, e1009261 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Garrett, W. S. The gut microbiota and colon cancer. Science 364, 1133–1135 (2019).

    Article  CAS  PubMed  Google Scholar 

  86. Zagato, E. et al. Endogenous murine microbiota member Faecalibaculum rodentium and its human homologue protect from intestinal tumour growth. Nat. Microbiol. 5, 511–524 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Nelson, D. P. & Mata, L. J. Bacterial flora associated with the human gastrointestinal mucosa. Gastroenterology 58, 56–61 (1970).

    Article  CAS  PubMed  Google Scholar 

  88. Kaper, J. B., Nataro, J. P. & Mobley, H. L. Pathogenic Escherichia coli. Nat. Rev. Microbiol. 2, 123–140 (2004).

    Article  CAS  PubMed  Google Scholar 

  89. Denamur, E., Clermont, O., Bonacorsi, S. & Gordon, D. The population genetics of pathogenic Escherichia coli. Nat. Rev. Microbiol. 19, 37–54 (2021).

    Article  CAS  PubMed  Google Scholar 

  90. Vizcaino, M. I. & Crawford, J. M. The colibactin warhead crosslinks DNA. Nat. Chem. 7, 411–417 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Bossuet-Greif, N. et al. The colibactin genotoxin generates DNA interstrand cross-links in infected cells. mBio 9, e02393-17 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  92. Wilson, M. R. et al. The human gut bacterial genotoxin colibactin alkylates DNA. Science 363, eaar7785 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Putze, J. et al. Genetic structure and distribution of the colibactin genomic island among members of the family Enterobacteriaceae. Infect. Immun. 77, 4696–4703 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Dougherty, M. W. & Jobin, C. Shining a light on colibactin biology. Toxins 13, 346 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Fu, D., Calvo, J. A. & Samson, L. D. Balancing repair and tolerance of DNA damage caused by alkylating agents. Nat. Rev. Cancer 12, 104–120 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Tripathi, P. et al. ClbS is a cyclopropane hydrolase that confers colibactin resistance. J. Am. Chem. Soc. 139, 17719–17722 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Sadecki, P. W. et al. Evolution of polymyxin resistance regulates colibactin production in Escherichia coli. ACS Chem. Biol. 16, 1243–1254 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Rehm, N. et al. Two polyketides intertwined in complex regulation: posttranscriptional CsrA-mediated control of colibactin and yersiniabactin synthesis in Escherichia coli. mBio 13, e0381421 (2022).

    Article  Google Scholar 

  99. Faïs, T., Delmas, J., Barnich, N., Bonnet, R. & Dalmasso, G. Colibactin: more than a new bacterial toxin. Toxins 10, E151 (2018).

    Article  Google Scholar 

  100. Wallenstein, A. et al. ClbR is the key transcriptional activator of colibactin gene expression in Escherichia coli. mSphere 5, e00591-20 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  101. Volpe, M. R. et al. A small molecule inhibitor prevents gut bacterial genotoxin production. Nat. Chem. Biol. 19, 159–167 (2023).

    Article  CAS  PubMed  Google Scholar 

  102. He, Z. et al. Campylobacter jejuni promotes colorectal tumorigenesis through the action of cytolethal distending toxin. Gut 68, 289–300 (2019).

    Article  CAS  PubMed  Google Scholar 

  103. Man, S. M. The clinical importance of emerging Campylobacter species. Nat. Rev. Gastroenterol. Hepatol. 8, 669–685 (2011).

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  105. Endo, A., Pärtty, A., Kalliomäki, M., Isolauri, E. & Salminen, S. Long-term monitoring of the human intestinal microbiota from the 2nd week to 13 years of age. Anaerobe 28, 149–156 (2014).

    Article  PubMed  Google Scholar 

  106. Carrow, H. C., Batachari, L. E. & Chu, H. Strain diversity in the microbiome: lessons from Bacteroides fragilis. PLoS Pathog. 16, e1009056 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Sears, C. L., Geis, A. L. & Housseau, F. Bacteroides fragilis subverts mucosal biology: from symbiont to colon carcinogenesis. J. Clin. Invest. 124, 4166–4172 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Round, J. L. & Mazmanian, S. K. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc. Natl Acad. Sci. USA 107, 12204–12209 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Mazmanian, S. K., Liu, C. H., Tzianabos, A. O. & Kasper, D. L. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122, 107–118 (2005).

    Article  CAS  PubMed  Google Scholar 

  110. 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).

    Article  CAS  PubMed  Google Scholar 

  111. 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 

  112. Wu, S., Morin, P. J., Maouyo, D. & Sears, C. L. Bacteroides fragilis enterotoxin induces c-Myc expression and cellular proliferation. Gastroenterology 124, 392–400 (2003).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  114. Wu, S. 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-κB pathway. Infect. Immun. 72, 5832–5839 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Cheng, W. T., Kantilal, H. K. & Davamani, F. The mechanism of Bacteroides fragilis toxin contributes to colon cancer formation. Malays. J. Med. Sci. 27, 9–21 (2020).

    PubMed  PubMed Central  Google Scholar 

  116. Liu, Q.-Q. et al. Enterotoxigenic Bacteroides fragilis induces the stemness in colorectal cancer via upregulating histone demethylase JMJD2B. Gut Microbes 12, 1788900 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  117. Dejea, C. M. et al. Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. Science 359, 592–597 (2018). This study shows that mice co-colonized with the bacterial biofilms found in patients with adenomatous polyposis exhibit increased inflammation and DNA damage in the colon, faster tumour onset and increased mortality compared with mice with only one bacterial strain.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Pagès, F. et al. Effector memory T cells, early metastasis, and survival in colorectal cancer. N. Engl. J. Med. 353, 2654–2666 (2005).

    Article  PubMed  Google Scholar 

  119. Sinicrope, F. A. et al. Intraepithelial effector (CD3+)/regulatory (FoxP3+) T-cell ratio predicts a clinical outcome of human colon carcinoma. Gastroenterology 137, 1270–1279 (2009).

    Article  CAS  PubMed  Google Scholar 

  120. Allen, J. et al. Colon tumors in enterotoxigenic Bacteroides fragilis (ETBF)-colonized mice do not display a unique mutational signature but instead possess host-dependent alterations in the APC gene. Microbiol. Spectr. 10, e0105522 (2022).

    Article  PubMed  Google Scholar 

  121. Yu, J. et al. Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut 66, 70–78 (2017).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  123. Degirolamo, C., Modica, S., Palasciano, G. & Moschetta, A. Bile acids and colon cancer: solving the puzzle with nuclear receptors. Trends Mol. Med. 17, 564–572 (2011).

    Article  CAS  PubMed  Google Scholar 

  124. Attard, G., Cooper, C. S. & de Bono, J. S. Steroid hormone receptors in prostate cancer: a hard habit to break? Cancer Cell 16, 458–462 (2009).

    Article  CAS  PubMed  Google Scholar 

  125. Tsoi, H. et al. Peptostreptococcus anaerobius induces intracellular cholesterol biosynthesis in colon cells to induce proliferation and causes dysplasia in mice. Gastroenterology 152, 1419–1433.e5 (2017).

    Article  PubMed  Google Scholar 

  126. Long, X. et al. Peptostreptococcus anaerobius promotes colorectal carcinogenesis and modulates tumour immunity. Nat. Microbiol. 4, 2319–2330 (2019).

    Article  PubMed  Google Scholar 

  127. Veglia, F., Sanseviero, E. & Gabrilovich, D. I. Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity. Nat. Rev. Immunol. 21, 485–498 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Gabrilovich, D. I. Myeloid-derived suppressor cells. Cancer Immunol. Res. 5, 3–8 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Huang, B., Song, B. & Xu, C. Cholesterol metabolism in cancer: mechanisms and therapeutic opportunities. Nat. Metab. 2, 132–141 (2020).

    Article  PubMed  Google Scholar 

  130. McDonald, L. C. et al. Clinical Practice Guidelines for Clostridium difficile infection in adults and children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin. Infect. Dis. 66, e1–e48 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Farrow, M. A. et al. Clostridium difficile toxin B-induced necrosis is mediated by the host epithelial cell NADPH oxidase complex. Proc. Natl Acad. Sci. USA 110, 18674–18679 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Fukugaiti, M. H. et al. High occurrence of Fusobacterium nucleatum and Clostridium difficile in the intestinal microbiota of colorectal carcinoma patients. Braz. J. Microbiol. Publ. Braz. Soc. Microbiol. 46, 1135–1140 (2015).

    Article  CAS  Google Scholar 

  134. Magat, E. M. et al. Clostridioides difficile antibody response of colorectal cancer patients versus clinically healthy individuals. Biosci. Microbiota Food Health 39, 123–127 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Cao, Y. et al. Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites. Science 378, eabm3233 (2022). This study identifies a new family of genotoxins called indolimines produced by M. morganii, a gut bacterium associated with CRC.

    Article  CAS  PubMed  Google Scholar 

  136. Brennan, C. A. & Garrett, W. S. Fusobacterium nucleatum — symbiont, opportunist and oncobacterium. Nat. Rev. Microbiol. 17, 156–166 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Hajishengallis, G. Periodontitis: from microbial immune subversion to systemic inflammation. Nat. Rev. Immunol. 15, 30–44 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. 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).

    Article  PubMed Central  Google Scholar 

  141. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. 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 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  145. 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).

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Abed, J. et al. Colon cancer-associated Fusobacterium nucleatum may originate from the oral cavity and reach colon tumors via the circulatory system. Front. Cell. Infect. Microbiol. 10, 400 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Thomas, A. M. et al. Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation. Nat. Med. 25, 667–678 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Kölbl, A. C., Jeschke, U., Friese, K. & Andergassen, U. The role of TF- and Tn-antigens in breast cancer metastasis. Histol. Histopathol. 31, 613–621 (2016).

    PubMed  Google Scholar 

  153. Patil, S. A. et al. Overexpression of α2,3sialyl T-antigen in breast cancer determined by miniaturized glycosyltransferase assays and confirmed using tissue microarray immunohistochemical analysis. Glycoconj. J. 31, 509–521 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Bertocchi, A. et al. Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver. Cancer Cell 39, 708–724.e11 (2021).

    Article  CAS  PubMed  Google Scholar 

  156. 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.e24 (2017).

    Article  CAS  PubMed  Google Scholar 

  157. Yu, T. et al. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell 170, 548–563.e16 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Loesche, W. J. & Gibbons, R. J. Amino acid fermentation by Fusobacterium nucleatum. Arch. Oral. Biol. 13, 191–202 (1968).

    Article  CAS  PubMed  Google Scholar 

  159. Cummings, J. H., Pomare, E. W., Branch, W. J., Naylor, C. P. & Macfarlane, G. T. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 28, 1221–1227 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Smith, P. M. et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341, 569–573 (2013).

    Article  CAS  PubMed  Google Scholar 

  161. Arpaia, N. et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504, 451–455 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Macia, L. et al. Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. Nat. Commun. 6, 6734 (2015).

    Article  CAS  PubMed  Google Scholar 

  163. Chun, E. et al. Metabolite-sensing receptor Ffar2 regulates colonic group 3 innate lymphoid cells and gut immunity. Immunity 51, 871–884.e6 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Lavoie, S. et al. Expression of free fatty acid receptor 2 by dendritic cells prevents their expression of interleukin 27 and is required for maintenance of mucosal barrier and immune response against colorectal tumors in mice. Gastroenterology 158, 1359–1372.e9 (2020).

    Article  CAS  PubMed  Google Scholar 

  165. Tan, J. et al. The role of short-chain fatty acids in health and disease. Adv. Immunol. 121, 91–119 (2014).

    Article  CAS  PubMed  Google Scholar 

  166. Le Poul, E. et al. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J. Biol. Chem. 278, 25481–25489 (2003).

    Article  PubMed  Google Scholar 

  167. Brennan, C. A. et al. Fusobacterium nucleatum drives a pro-inflammatory intestinal microenvironment through metabolite receptor-dependent modulation of IL-17 expression. Gut Microbes 13, 1987780 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  168. Ternes, D. et al. The gut microbial metabolite formate exacerbates colorectal cancer progression. Nat. Metab. 4, 458–475 (2022). This study uncovers a novel pro-tumorigenic function of the CRC-associated bacterium F. nucleatum by producing formate, a metabolite that triggers AhR signalling further increasing cancer stemness, tumour invasion and TH17 cell expansion.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Cluntun, A. A., Lukey, M. J., Cerione, R. A. & Locasale, J. W. Glutamine metabolism in cancer: understanding the heterogeneity. Trends Cancer 3, 169–180 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Pavlova, N. N. & Thompson, C. B. The emerging hallmarks of cancer metabolism. Cell Metab. 23, 27–47 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Stanford, E. A. et al. The role of the aryl hydrocarbon receptor in the development of cells with the molecular and functional characteristics of cancer stem-like cells. BMC Biol. 14, 20 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  172. Queen, J. et al. Comparative analysis of colon cancer-derived Fusobacterium nucleatum subspecies: inflammation and colon tumorigenesis in murine models. mBio 13, e0299121 (2022).

    Article  Google Scholar 

  173. Mizrahi, J. D., Surana, R., Valle, J. W. & Shroff, R. T. Pancreatic cancer. Lancet 395, 2008–2020 (2020).

    Article  CAS  PubMed  Google Scholar 

  174. Mitsuhashi, K. et al. Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis. Oncotarget 6, 7209–7220 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  175. Farrell, J. J. et al. Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer. Gut 61, 582–588 (2012).

    Article  CAS  PubMed  Google Scholar 

  176. Geller, L. T. et al. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science 357, 1156–1160 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Saunders, C. W., Scheynius, A. & Heitman, J. Malassezia fungi are specialized to live on skin and associated with dandruff, eczema, and other skin diseases. PLoS Pathog. 8, e1002701 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Afshar-Kharghan, V. The role of the complement system in cancer. J. Clin. Invest. 127, 780–789 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  179. Nakatsu, G. et al. Alterations in enteric virome are associated with colorectal cancer and survival outcomes. Gastroenterology 155, 529–541.e5 (2018).

    Article  PubMed  Google Scholar 

  180. Thai, A. A., Solomon, B. J., Sequist, L. V., Gainor, J. F. & Heist, R. S. Lung cancer. Lancet 398, 535–554 (2021).

    Article  PubMed  Google Scholar 

  181. Dickson, R. P., Erb-Downward, J. R., Martinez, F. J. & Huffnagle, G. B. The microbiome and the respiratory tract. Annu. Rev. Physiol. 78, 481–504 (2016).

    Article  CAS  PubMed  Google Scholar 

  182. Willis, A. L., Calton, J. B., Carr, T. F., Chiu, A. G. & Chang, E. H. Dead or alive: deoxyribonuclease I sensitive bacteria and implications for the sinus microbiome. Am. J. Rhinol. Allergy 30, 94–98 (2016).

    Article  PubMed  Google Scholar 

  183. Segal, L. N. et al. Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation. Microbiome 1, 19 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  184. Remot, A. et al. Bacteria isolated from lung modulate asthma susceptibility in mice. ISME J. 11, 1061–1074 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Hsu-Kim, C., Hoag, J. B., Cheng, G.-S. & Lund, M. E. The microbiology of postobstructive pneumonia in lung cancer patients. J. Bronchol. Interv. Pulmonol. 20, 266–270 (2013).

    Article  Google Scholar 

  186. Littman, A. J., Jackson, L. A. & Vaughan, T. L. Chlamydia pneumoniae and lung cancer: epidemiologic evidence. Cancer Epidemiol. Biomark. Prev. 14, 773–778 (2005).

    Article  CAS  Google Scholar 

  187. Tsay, J.-C. J. et al. Airway microbiota is associated with upregulation of the PI3K pathway in lung cancer. Am. J. Respir. Crit. Care Med. 198, 1188–1198 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Jin, C. et al. Commensal microbiota promote lung cancer development via γδ T cells. Cell 176, 998–1013.e16 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Gadelle, D., Raibaud, P. & Sacquet, E. β-Glucuronidase activities of intestinal bacteria determined both in vitro and in vivo in gnotobiotic rats. Appl. Environ. Microbiol. 49, 682–685 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Dabek, M., McCrae, S. I., Stevens, V. J., Duncan, S. H. & Louis, P. Distribution of β-glucosidase and β-glucuronidase activity and of β-glucuronidase gene gus in human colonic bacteria. FEMS Microbiol. Ecol. 66, 487–495 (2008).

    Article  CAS  PubMed  Google Scholar 

  191. Kwa, M., Plottel, C. S., Blaser, M. J. & Adams, S. The intestinal microbiome and estrogen receptor-positive female breast cancer. J. Natl. Cancer Inst. 108, djw029 (2016).

    PubMed  PubMed Central  Google Scholar 

  192. Flores, R. et al. Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: a cross-sectional study. J. Transl. Med. 10, 253 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Fu, A. et al. Tumor-resident intracellular microbiota promotes metastatic colonization in breast cancer. Cell 185, 1356–1372.e26 (2022). This work shows that the tumour-resident intracellular microbiota promotes metastases.

    Article  CAS  PubMed  Google Scholar 

  194. Mikó, E. et al. Lithocholic acid, a bacterial metabolite reduces breast cancer cell proliferation and aggressiveness. Biochim. Biophys. Acta Bioenerg. 1859, 958–974 (2018).

    Article  PubMed  Google Scholar 

  195. Thirunavukkarasan, M. et al. Short-chain fatty acid receptors inhibit invasive phenotypes in breast cancer cells. PLoS ONE 12, e0186334 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  196. Ridlon, J. M., Kang, D.-J. & Hylemon, P. B. Bile salt biotransformations by human intestinal bacteria. J. Lipid Res. 47, 241–259 (2006).

    Article  CAS  PubMed  Google Scholar 

  197. Wirbel, J. et al. Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. Nat. Med. 25, 679–689 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Ma, C. et al. Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells. Science 360, eaan5931 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  199. Kang, D. Clostridium scindens baiCD and baiH genes encode stereo-specific 7α/7β-hydroxy-3-oxo-Δ4-cholenoic acid oxidoreductases. Biochim. Biophys. Acta 1781, 16–25 (2008).

    Article  CAS  PubMed  Google Scholar 

  200. Pols, T. W. H., Noriega, L. G., Nomura, M., Auwerx, J. & Schoonjans, K. The bile acid membrane receptor TGR5: a valuable metabolic target. Dig. Dis. 29, 37–44 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  201. Terrisse, S. et al. Intestinal microbiota influences clinical outcome and side effects of early breast cancer treatment. Cell Death Differ. 28, 2778–2796 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Abed, J. et al. Tumor targeting by fusobacterium nucleatum: a pilot study and future perspectives. Front. Cell. Infect. Microbiol. 7, 295 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  203. Patel, A. R. & Klein, E. A. Risk factors for prostate cancer. Nat. Clin. Pract. Urol. 6, 87–95 (2009).

    Article  PubMed  Google Scholar 

  204. Chan, J. M., Gann, P. H. & Giovannucci, E. L. Role of diet in prostate cancer development and progression. J. Clin. Oncol. 23, 8152–8160 (2005).

    Article  CAS  PubMed  Google Scholar 

  205. Feng, Y. et al. Metagenomic and metatranscriptomic analysis of human prostate microbiota from patients with prostate cancer. BMC Genomics 20, 146 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  206. Cavarretta, I. et al. The microbiome of the prostate tumor microenvironment. Eur. Urol. 72, 625–631 (2017).

    Article  CAS  PubMed  Google Scholar 

  207. Liss, M. A. et al. Metabolic biosynthesis pathways identified from fecal microbiome associated with prostate cancer. Eur. Urol. 74, 575–582 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Golombos, D. M. et al. The role of gut microbiome in the pathogenesis of prostate cancer: a prospective, pilot study. Urology 111, 122–128 (2018).

    Article  PubMed  Google Scholar 

  209. Pernigoni, N. et al. Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis. Science 374, 216–224 (2021). This study shows that the gut microbiota contributes to the onset of castration-resistant prostate cancer by promoting the expansion of species capable of converting androgen precursors into active androgens.

    Article  CAS  PubMed  Google Scholar 

  210. Terrisse, S. et al. Immune system and intestinal microbiota determine efficacy of androgen deprivation therapy against prostate cancer. J. Immunother. Cancer 10, e004191 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  211. Matsushita, M. et al. Gut microbiota-derived short-chain fatty acids promote prostate cancer growth via IGF1 signaling. Cancer Res. 81, 4014–4026 (2021).

    Article  CAS  PubMed  Google Scholar 

  212. Daisley, B. A. et al. Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients. Nat. Commun. 11, 4822 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  213. Terrisse, S., Zitvogel, L. & Kroemer, G. Effects of the intestinal microbiota on prostate cancer treatment by androgen deprivation therapy. Microb. Cell Graz Austria 9, 202–206 (2022).

    Google Scholar 

  214. Navarro, M., Nicolas, A., Ferrandez, A. & Lanas, A. Colorectal cancer population screening programs worldwide in 2016: an update. World J. Gastroenterol. 23, 3632 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  215. Wolf, A. M. D. et al. Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. Ca. Cancer J. Clin. 68, 250–281 (2018).

    Article  PubMed  Google Scholar 

  216. Kartal, E. et al. A faecal microbiota signature with high specificity for pancreatic cancer. Gut 71, 1359–1372 (2022).

    Article  CAS  PubMed  Google Scholar 

  217. Kalaora, S. et al. Identification of bacteria-derived HLA-bound peptides in melanoma. Nature 592, 138–143 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  219. McNeil, J. J. et al. Effect of aspirin on all-cause mortality in the healthy elderly. N. Engl. J. Med. 379, 1519–1528 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  220. Chan, A. T., Ogino, S. & Fuchs, C. S. Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N. Engl. J. Med. 356, 2131–2142 (2007).

    Article  CAS  PubMed  Google Scholar 

  221. Chan, A. T. et al. Aspirin in the chemoprevention of colorectal neoplasia: an overview. Cancer Prev. Res. 5, 164–178 (2012).

    Article  CAS  Google Scholar 

  222. Guo, C.-G. et al. Aspirin use and risk of colorectal cancer among older adults. JAMA Oncol. 7, 428 (2021).

    Article  PubMed  Google Scholar 

  223. Prizment, A. E. et al. Randomised clinical study: oral aspirin 325 mg daily vs placebo alters gut microbial composition and bacterial taxa associated with colorectal cancer risk. Aliment. Pharmacol. Ther. 52, 976–987 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  224. Brennan, C. A. et al. Aspirin modulation of the colorectal cancer-associated microbe Fusobacterium nucleatum. mBio 12, e00547-21 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  225. Wang, W. H. et al. Aspirin inhibits the growth of Helicobacter pylori and enhances its susceptibility to antimicrobial agents. Gut 52, 490–495 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  226. Cederlund, H. & Mårdh, P. A. Antibacterial activities of non-antibiotic drugs. J. Antimicrob. Chemother. 32, 355–365 (1993).

    Article  CAS  PubMed  Google Scholar 

  227. Afzal, M. & Shafeeq, S. Impact of aspirin on the transcriptome of Streptococcus pneumoniae D39. Genom. Data 12, 38–40 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  228. Kunin, C. M., Hua, T. H., Guerrant, R. L. & Bakaletz, L. O. Effect of salicylate, bismuth, osmolytes, and tetracycline resistance on expression of fimbriae by Escherichia coli. Infect. Immun. 62, 2178–2186 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Rosner, J. L., Chai, T. J. & Foulds, J. Regulation of ompF porin expression by salicylate in Escherichia coli. J. Bacteriol. 173, 5631–5638 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  230. Kupferwasser, L. I. et al. Salicylic acid attenuates virulence in endovascular infections by targeting global regulatory pathways in Staphylococcus aureus. J. Clin. Invest. 112, 222–233 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  231. Sonnenburg, E. D. et al. Diet-induced extinctions in the gut microbiota compound over generations. Nature 529, 212–215 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  232. David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2014).

    Article  CAS  PubMed  Google Scholar 

  233. Giovannucci, E. & Willett, W. C. Dietary factors and risk of colon cancer. Ann. Med. 26, 443–452 (1994).

    Article  CAS  PubMed  Google Scholar 

  234. Bouvard, V. et al. Carcinogenicity of consumption of red and processed meat. Lancet Oncol. 16, 1599–1600 (2015).

    Article  PubMed  Google Scholar 

  235. Gurjao, C. et al. Discovery and features of an alkylating signature in colorectal cancer. Cancer Discov. 11, 2446–2455 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  236. 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).

    Article  PubMed  PubMed Central  Google Scholar 

  237. Łusiak-Szelachowska, M., Weber-Dąbrowska, B., Jończyk-Matysiak, E., Wojciechowska, R. & Górski, A. Bacteriophages in the gastrointestinal tract and their implications. Gut Pathog. 9, 44 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  238. Sulakvelidze, A., Alavidze, Z. & Morris, J. G. Bacteriophage therapy. Antimicrob. Agents Chemother. 45, 649–659 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  239. d’Herelle, F. Bacteriophage as a treatment in acute medical and surgical infections. Bull. N. Y. Acad. Med. 7, 329–348 (1931).

    PubMed  PubMed Central  Google Scholar 

  240. Cieplak, T., Soffer, N., Sulakvelidze, A. & Nielsen, D. S. A bacteriophage cocktail targeting Escherichia coli reduces E. coli in simulated gut conditions, while preserving a non-targeted representative commensal normal microbiota. Gut Microbes 9, 391–399 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  241. Cuomo, P. et al. An innovative approach to control H. pylori-induced persistent inflammation and colonization. Microorganisms 8, E1214 (2020).

    Article  Google Scholar 

  242. Zheng, D.-W. et al. Phage-guided modulation of the gut microbiota of mouse models of colorectal cancer augments their responses to chemotherapy. Nat. Biomed. Eng. 3, 717–728 (2019).

    Article  CAS  PubMed  Google Scholar 

  243. Zhou, S., Gravekamp, C., Bermudes, D. & Liu, K. Tumour-targeting bacteria engineered to fight cancer. Nat. Rev. Cancer 18, 727–743 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  244. Lynch, J. P., Goers, L. & Lesser, C. F. Emerging strategies for engineering Escherichia coli Nissle 1917-based therapeutics. Trends Pharmacol. Sci. 43, 772–786 (2022).

    Article  CAS  PubMed  Google Scholar 

  245. Nißle, A. Weiteres über Grundlagen und Praxis der mutaflorbehandlung [German]. Dtsch. Med. Wochenschr. 51, 1809–1813 (1925).

    Article  Google Scholar 

  246. Zhou, Y. & Han, Y. Engineered bacteria as drug delivery vehicles: principles and prospects. Eng. Microbiol. 2, 100034 (2022).

    Article  CAS  Google Scholar 

  247. Ho, C. L. et al. Engineered commensal microbes for diet-mediated colorectal-cancer chemoprevention. Nat. Biomed. Eng. 2, 27–37 (2018).

    Article  CAS  PubMed  Google Scholar 

  248. Leventhal, D. S. et al. Immunotherapy with engineered bacteria by targeting the STING pathway for anti-tumor immunity. Nat. Commun. 11, 2739 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  249. Gurbatri, C. R. et al. Engineered probiotics for local tumor delivery of checkpoint blockade nanobodies. Sci. Transl. Med. 12, eaax0876 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  250. Sonnenborn, U. & Schulze, J. The non-pathogenic Escherichia coli strain Nissle 1917 — features of a versatile probiotic. Microb. Ecol. Health Dis. 21, 122–158 (2009).

    CAS  Google Scholar 

  251. Canale, F. P. et al. Metabolic modulation of tumours with engineered bacteria for immunotherapy. Nature 598, 662–666 (2021).

    Article  CAS  PubMed  Google Scholar 

  252. Chowdhury, S. et al. Programmable bacteria induce durable tumor regression and systemic antitumor immunity. Nat. Med. 25, 1057–1063 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  253. Geiger, R. et al. l-Arginine modulates T cell metabolism and enhances survival and anti-tumor activity. Cell 167, 829–842.e13 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  254. van Niel, G., D’Angelo, G. & Raposo, G. Shedding light on the cell biology of extracellular vesicles. Nat. Rev. Mol. Cell Biol. 19, 213–228 (2018).

    Article  PubMed  Google Scholar 

  255. Yu, W. et al. Exosome-based liquid biopsies in cancer: opportunities and challenges. Ann. Oncol. 32, 466–477 (2021).

    Article  CAS  PubMed  Google Scholar 

  256. Kim, O. Y. et al. Bacterial outer membrane vesicles suppress tumor by interferon-γ-mediated antitumor response. Nat. Commun. 8, 626 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  257. Cheng, L. & Hill, A. F. Therapeutically harnessing extracellular vesicles. Nat. Rev. Drug Discov. 21, 379–399 (2022).

    Article  CAS  PubMed  Google Scholar 

  258. Chronopoulos, A. & Kalluri, R. Emerging role of bacterial extracellular vesicles in cancer. Oncogene 39, 6951–6960 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  259. Borst, J., Ahrends, T., Bąbała, N., Melief, C. J. M. & Kastenmüller, W. CD4+ T cell help in cancer immunology and immunotherapy. Nat. Rev. Immunol. 18, 635–647 (2018).

    Article  CAS  PubMed  Google Scholar 

  260. Ivanov, I. I. et al. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe 4, 337–349 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  261. Tanoue, T. et al. A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Nature 565, 600–605 (2019). This study shows that a consortium of 11 bacterial strains from human faeces induces IFNγ-producing CD8+ T cells in the intestine without causing inflammation and could therefore potentially be used as biotherapeutics to enhance host immunity against infections and cancer.

    Article  CAS  PubMed  Google Scholar 

  262. Luckheeram, R. V., Zhou, R., Verma, A. D. & Xia, B. CD4+ T cells: differentiation and functions. Clin. Dev. Immunol. 2012, 925135 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  263. Belkaid, Y. & Hand, T. W. Role of the microbiota in immunity and inflammation. Cell 157, 121–141 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  264. Harrington, L. E. et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat. Immunol. 6, 1123–1132 (2005).

    Article  CAS  PubMed  Google Scholar 

  265. Wang, K. et al. Interleukin-17 receptor a signaling in transformed enterocytes promotes early colorectal tumorigenesis. Immunity 41, 1052–1063 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  266. Calcinotto, A. et al. Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression. Nat. Commun. 9, 4832 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  267. Atarashi, K. et al. TH17 cell induction by adhesion of microbes to intestinal epithelial cells. Cell 163, 367–380 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  268. Tan, T. G. et al. Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal TH17 cells in mice. Proc. Natl Acad. Sci. USA 113, E8141–E8150 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  269. Overacre-Delgoffe, A. E. et al. Microbiota-specific T follicular helper cells drive tertiary lymphoid structures and anti-tumor immunity against colorectal cancer. Immunity 54, 2812–2824.e4 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  270. Chen, M.-L. et al. Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-β signals in vivo. Proc. Natl Acad. Sci. USA 102, 419–424 (2005).

    Article  CAS  PubMed  Google Scholar 

  271. Daillère, R. et al. Enterococcus hirae and Barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects. Immunity 45, 931–943 (2016).

    Article  PubMed  Google Scholar 

  272. Bachem, A. et al. Microbiota-derived short-chain fatty acids promote the memory potential of antigen-activated CD8+ T cells. Immunity 51, 285–297.e5 (2019).

    Article  CAS  PubMed  Google Scholar 

  273. Yu, A. I. et al. Gut microbiota modulate CD8 T cell responses to influence colitis-associated tumorigenesis. Cell Rep. 31, 107471 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  274. Nakatsuji, T. et al. A commensal strain of Staphylococcus epidermidis protects against skin neoplasia. Sci. Adv. 4, eaao4502 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  275. Mrázek, J. et al. Melanoma-related changes in skin microbiome. Folia Microbiol. 64, 435–442 (2019).

    Article  Google Scholar 

  276. Byrd, A. L., Belkaid, Y. & Segre, J. A. The human skin microbiome. Nat. Rev. Microbiol. 16, 143–155 (2018).

    Article  CAS  PubMed  Google Scholar 

  277. Naik, S. et al. Compartmentalized control of skin immunity by resident commensals. Science 337, 1115–1119 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  278. Naik, S. et al. Commensal–dendritic-cell interaction specifies a unique protective skin immune signature. Nature 520, 104–108 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  279. Chehoud, C. et al. Complement modulates the cutaneous microbiome and inflammatory milieu. Proc. Natl Acad. Sci. USA 110, 15061–15066 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  280. Grice, E. A. et al. Topographical and temporal diversity of the human skin microbiome. Science 324, 1190–1192 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  281. 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 

  282. Belkaid, Y. & Segre, J. A. Dialogue between skin microbiota and immunity. Science 346, 954–959 (2014).

    Article  CAS  PubMed  Google Scholar 

  283. Chen, Y. E., Fischbach, M. A. & Belkaid, Y. Skin microbiota–host interactions. Nature 553, 427–436 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  284. Markle, J. G. M. et al. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science 339, 1084–1088 (2013). This study shows that early-life microbial exposures can affect the progression of type 1 diabetes in male mice by regulating sex hormone levels.

    Article  CAS  PubMed  Google Scholar 

  285. Miller, W. L. & Auchus, R. J. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr. Rev. 32, 81–151 (2011).

    Article  CAS  PubMed  Google Scholar 

  286. Vemuri, R. et al. The microgenderome revealed: sex differences in bidirectional interactions between the microbiota, hormones, immunity and disease susceptibility. Semin. Immunopathol. 41, 265–275 (2019).

    Article  PubMed  Google Scholar 

  287. Schwabe, R. F. & Jobin, C. The microbiome and cancer. Nat. Rev. Cancer 13, 800–812 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  288. Plottel, C. S. & Blaser, M. J. Microbiome and malignancy. Cell Host Microbe 10, 324–335 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  289. Colldén, H. et al. The gut microbiota is a major regulator of androgen metabolism in intestinal contents. Am. J. Physiol. Endocrinol. Metab. 317, E1182–E1192 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  290. Pala, L. et al. Sex differences in efficacy and toxicity of systemic cancer treatments: role of the microbiome. J. Clin. Oncol. 37, 439 (2019).

    Article  CAS  PubMed  Google Scholar 

  291. Pelka, K. et al. Spatially organized multicellular immune hubs in human colorectal cancer. Cell 184, 4734–4752.e20 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  292. Rao, A., Barkley, D., França, G. S. & Yanai, I. Exploring tissue architecture using spatial transcriptomics. Nature 596, 211–220 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  293. Dar, D., Dar, N., Cai, L. & Newman, D. K. Spatial transcriptomics of planktonic and sessile bacterial populations at single-cell resolution. Science 373, eabi4882 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  294. Shi, H. et al. Highly multiplexed spatial mapping of microbial communities. Nature 588, 676–681 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  295. Galeano Niño, J. L. et al. Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer. Nature 611, 810–817 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work is supported by National Institutes of Health (NIH) grant R01CA154426 and the Cancer Research UK Grand Challenge Initiative C10674/A27140 to W.S.G. G.E.T. is the recipient of a European Molecular Biology Organization (EMBO) Postdoctoral Fellowship (ALTF 1020-2021). The authors thank all Garrett laboratory members for helpful discussions and contributions.

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Authors and Affiliations

  1. Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA

    Geniver El Tekle & Wendy S. Garrett

  2. The Harvard T. H. Chan Microbiome in Public Health Center, Boston, MA, USA

    Geniver El Tekle & Wendy S. Garrett

  3. The Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Geniver El Tekle & Wendy S. Garrett

  4. Department of Medicine, Harvard Medical School, Boston, MA, USA

    Wendy S. Garrett

  5. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Wendy S. Garrett

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  1. Geniver El Tekle
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All authors contributed equally to all aspects of the article.

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Correspondence to Wendy S. Garrett.

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Competing interests

W.S.G. is on the scientific advisory board of Freya Biosciences, Scipher Medicine and Senda Biosciences, all outside the current work. W.S.G.’s laboratory receives funding from Merck and Astellas. G.E.T. declares no competing interests.

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Glossary

γ-H2AX

A sensitive marker of DNA damage, as phosphorylation of H2AX is required for the assembly of the DNA double-strand repair machinery.

Apc Min/+ mouse model

Mice carrying a heterogeneous mutation in the commonly mutated (more than 80% of patients with colon cancer) adenomatous polyposis coli (APC) gene that develop spontaneous intestinal adenomas.

Azoxymethane (AOM)–dextran sodium sulfate (DSS) mouse model

A chemically inducible mouse model of colitis-associated colon cancer, where mice are treated with AOM, a jet fuel-derived mutagenic agent that damages the DNA of colonic epithelial cells, followed by three cycles of mucosal disruptant DSS.

Bacterial species

Bacteria sharing common genomic features and exhibiting a high degree of similarity in phenotype.

Bacterial strain

A genetic variant of a particular species of bacteria.

Bacteriophages

Viruses that infect and replicate within bacteria.

Biogeography

Localization at particular body sites.

Caecal microbiota transplant

(CMT). The transfer of caecal contents and microorganisms therein from a donor to a recipient host.

Faecal microbiota transplant

(FMT). The transfer of the microorganisms from the stool of a donor to a recipient.

Familial adenomatous polyposis

(FAP). A rare, autosomal dominant syndrome, involving the adenomatous polyposis coli (APC) gene, that predisposes an individual to tumours of the colon and rectum.

Genotoxic

A property that induces genetic damage (DNA mutation) within a cell.

Gnotobiotics

A specialized microbially controlled animal husbandry practice enabling experiments in which animals can be kept completely devoid of microorganisms or with defined microbial communities.

Gram-negative

A description of a bacterium that harbours an outer lipid membrane and does not retain crystal violet staining (Gram staining).

Gram-positive

A description of a bacterium that does not harbour an outer lipid membrane and thus retains crystal violet staining (Gram staining).

Microbiome

The collection of microorganisms (archaea, bacteria, fungi, protists and viruses) that inhabit a specific environment.

Mutational signature

The combination of mutations emerging from DNA damage and repair processes.

Oncomicrobe

Microorganisms with established features that influence cancer susceptibility and therapeutic response.

Symbionts

Organisms living in a neutral or beneficial way with their host.

Theranostic

The combination of therapeutics and diagnostics.

Type 3 secretion system

A bacterial complex or injectisome widely used by gram-negative bacteria to inject their effector molecules or toxins into host cells.

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El Tekle, G., Garrett, W.S. Bacteria in cancer initiation, promotion and progression. Nat Rev Cancer 23, 600–618 (2023). https://doi.org/10.1038/s41568-023-00594-2

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