CoChat
Sign Up
Cited by 359Gut microbiota and healthCancer Immunotherapy and BiomarkersBacterial Cancer Therapy

The DOI matches its Crossref record; its reference list is not available.

Role of the gut microbiota in anticancer therapy: from molecular mechanisms to clinical applications

Open access
Zhao, Lin-Yong, Mei, Jia-Xin, Yu, Gang, Lei, Lei, Zhang, Wei-Han, Liu, Kai, Chen, Xiao-Long, Kołat, Damian, Yang, Kun, Hu, Jian-Kun·2023·Signal Transduction and Targeted Therapy
DOI 10.1038/s41392-023-01406-7PMC PMC10183032
Open this paper in CoChat — free accountOpen PDF

Abstract

In the past period, due to the rapid development of next-generation sequencing technology, accumulating evidence has clarified the complex role of the human microbiota in the development of cancer and the therapeutic response. More importantly, available evidence seems to indicate that modulating the composition of the gut microbiota to improve the efficacy of anti-cancer drugs may be feasible. However, intricate complexities exist, and a deep and comprehensive understanding of how the human microbiota interacts with cancer is critical to realize its full potential in cancer treatment. The purpose of this review is to summarize the initial clues on molecular mechanisms regarding the mutual effects between the gut microbiota and cancer development, and to highlight the relationship between gut microbes and the efficacy of immunotherapy, chemotherapy, radiation therapy and cancer surgery, which may provide insights into the formulation of individualized therapeutic strategies for cancer management. In addition, the current and emerging microbial interventions for cancer therapy as well as their clinical applications are summarized. Although many challenges remain for now, the great importance and full potential of the gut microbiota cannot be overstated for the development of individualized anti-cancer strategies, and it is necessary to explore a holistic approach that incorporates microbial modulation therapy in cancer.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41392-023-01406-7

Cites

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The interplay between the gut microbiome and the tumor microenvironment constitutes a critical regulatory axis that modulates tumor initiation, growth, metastatic dissemination, and responsiveness to treatment.

    “Consequently, the interplay between the gut microbiome and the TME constitutes a critical regulatory axis that modulates tumor initiation, growth, metastatic dissemination, and responsiveness to treatment [11,43,45–47]”

    From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [43]

  • The gut microbiome is a modifiable risk factor in multiple cancer types, including colorectal, gastric, and pancreatic cancers.

    “The gut microbiome is increasingly recognized as a modifiable risk factor in multiple cancer types, including colorectal, gastric, and pancreatic cancers [12,41–43]”

    From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [43]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

No citation lists for this paper

No citation lists for this paper yet — checked again daily.

References 426 · Cited by 359

Research works printed but not linked: 340

  1. Martinez-Guryn, K., Leone, V. & Chang, E. B. Regional diversity of the gastrointestinal microbiome. Cell Host Microbe 26, 314–324 (2019). · DOI
  2. Kovatcheva-Datchary, P. et al. Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of prevotella. Cell Metab 22, 971–982 (2015). · DOI · Paper page
  3. Cahenzli, J., Köller, Y., Wyss, M., Geuking, M. B. & McCoy, K. D. Intestinal microbial diversity during early-life colonization shapes long-term IgE levels. Cell Host Microbe 14, 559–570 (2013). · DOI · Paper page
  4. Sender, R., Fuchs, S. & Milo, R. Are we really vastly outnumbered? revisiting the ratio of bacterial to host. Cells in Humans. Cell 164, 337–340 (2016).
  5. Gensollen, T., Iyer, S. S., Kasper, D. L. & Blumberg, R. S. How colonization by microbiota in early life shapes the immune system. Science 352, 539–544 (2016). · DOI · Paper page
  6. McNeil, N. I. The contribution of the large intestine to energy supplies in man. Am. J. Clin. Nutr. 39, 338–342 (1984). · DOI · Paper page
  7. Meisel, M. et al. Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host. Nature 557, 580–584 (2018). · DOI · Paper page
  8. Viennois, E., Gewirtz, A. T. & Chassaing, B. Connecting the dots: dietary fat, microbiota dysbiosis, altered metabolome, and colon cancer. Gastroenterology 162, 38–39 (2022). · DOI
  9. Liu, N. N. et al. Microbiome dysbiosis in lung cancer: from composition to therapy. NPJ Precis Oncol 4, 33 (2020). · DOI
  10. Verstraelen, H. Of microbes and women: BRCA1, vaginal microbiota, and ovarian cancer. Lancet Oncol 20, 1049–1051 (2019). · DOI
  11. Buchta Rosean, C. et al. Preexisting commensal dysbiosis is a host-intrinsic regulator of tissue inflammation and tumor cell dissemination in hormone receptor-positive breast cancer. Cancer Res. 79, 3662–3675 (2019). · DOI
  12. Parida, S. et al. A procarcinogenic colon microbe promotes breast tumorigenesis and metastatic progression and concomitantly activates notch and β-catenin axes. Cancer Discov 11, 1138–1157 (2021). · DOI
  13. Liou, J. M. et al. Screening and eradication of Helicobacter pylori for gastric cancer prevention: the Taipei global consensus. Gut 69, 2093–2112 (2020). · DOI
  14. Zhao, K. & Hu, Y. Microbiome harbored within tumors: a new chance to revisit our understanding of cancer pathogenesis and treatment. Signal Transduct Target Ther 5, 136 (2020). · DOI
  15. Heymann, C. J. F., Bard, J. M., Heymann, M. F., Heymann, D. & Bobin-Dubigeon, C. The intratumoral microbiome: Characterization methods and functional impact. Cancer Lett 522, 63–79 (2021). · DOI
  16. Wong-Rolle, A., Wei, H. K., Zhao, C. & Jin, C. Unexpected guests in the tumor microenvironment: microbiome in cancer. Protein Cell 12, 426–435 (2021). · DOI
  17. LaCourse, K. D. et al. The cancer chemotherapeutic 5-fluorouracil is a potent Fusobacterium nucleatum inhibitor and its activity is modified by intratumoral microbiota. Cell Rep. 41, 111625 (2022). · DOI
  18. Erdag, G. et al. Immunotype and immunohistologic characteristics of tumor-infiltrating immune cells are associated with clinical outcome in metastatic melanoma. Cancer Res. 72, 1070–1080 (2012). · DOI
  19. Kather, J. N. et al. Topography of cancer-associated immune cells in human solid tumors. Elife 7, e36967 (2018). · DOI
  20. Stearn, E. W., Sturdivant, B. F. & Stearn, A. E. The life history of a micro-parasite isolated from carcinomatous growths. Proc. Natl Acad. Sci. USA. 11, 662–669 (1925). · DOI
  21. Fu, A. et al. Tumor-resident intracellular microbiota promotes metastatic colonization in breast cancer. Cell 185, 1356–1372.e1326 (2022). · DOI · Paper page
  22. Dohlman, A. B. et al. A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors. Cell 185, 3807–3822.e3812 (2022). · DOI
  23. Kwon, S. K. et al. Human gastric microbiota transplantation recapitulates premalignant lesions in germ-free mice. Gut 71, 1266–1276 (2022). · DOI
  24. Palrasu, M. et al. Helicobacter pylori pathogen inhibits cellular responses to oncogenic stress and apoptosis. PLoS Pathog 18, e1010628 (2022). · DOI
  25. Kumar, R. et al. Streptococcus gallolyticus subsp. gallolyticus promotes colorectal tumor development. PLoS Pathog 13, e1006440 (2017). · DOI
  26. 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.e824 (2017). · DOI
  27. Yu, L. X. et al. Endotoxin accumulation prevents carcinogen-induced apoptosis and promotes liver tumorigenesis in rodents. Hepatology 52, 1322–1333 (2010). · DOI · Paper page
  28. Aykut, B. et al. The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL. Nature 574, 264–267 (2019). · DOI · Paper page
  29. Yu, Q. et al. Intestinal microbiota modulates pancreatic carcinogenesis through intratumoral natural killer cells. Gut Microbes 14, 2112881 (2022). · DOI
  30. Dong, J. et al. Oral microbiota affects the efficacy and prognosis of radiotherapy for colorectal cancer in mouse models. Cell Rep 37, 109886 (2021). · DOI
  31. Li, Z. et al. Gut microbiota modulate radiotherapy-associated antitumor immune responses against hepatocellular carcinoma Via STING signaling. Gut Microbes 14, 2119055 (2022). · DOI
  32. Xie, Y. et al. Microbiota in tumors: from understanding to application. Adv Sci. 9, e2200470 (2022). · DOI
  33. Plummer, M. et al. Global burden of cancers attributable to infections in 2012: a synthetic analysis. Lancet Glob Health 4, e609–e616 (2016). · DOI
  34. Pushalkar, S. et al. The pancreatic cancer microbiome promotes oncogenesis by induction of innate and adaptive immune suppression. Cancer Discov 8, 403–416 (2018). · DOI · Paper page
  35. Hexun, Z. et al. High abundance of Lachnospiraceae in the human gut microbiome is related to high immunoscores in advanced colorectal cancer. Cancer Immunol. Immunother. 75, 315–326 (2022).
  36. Bhatt, A. P., Redinbo, M. R. & Bultman, S. J. The role of the microbiome in cancer development and therapy. CA Cancer J. Clin 67, 326–344 (2017). · DOI · Paper page
  37. Doocey, C. M., Finn, K., Murphy, C. & Guinane, C. M. The impact of the human microbiome in tumorigenesis, cancer progression, and biotherapeutic development. BMC Microbiol 22, 53 (2022). · DOI
  38. 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-kappaB, and Up-regulating Expression of MicroRNA-21. Gastroenterology 152, 851–866.e824 (2017). · DOI
  39. Sayed, I. M. et al. Helicobacter pylori infection downregulates the DNA glycosylase NEIL2, resulting in increased genome damage and inflammation in gastric epithelial cells. J. Biol. Chem. 295, 11082–11098 (2020). · DOI
  40. Han, T. et al. H. pylori infection alters repair of DNA double-strand breaks via SNHG17. J. Clin. Investig. 130, 3901–3918 (2020). · DOI
  41. Yachida, S. et al. Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer. Nat. Med. 25, 968–976 (2019). · DOI · Paper page
  42. Garrett, W. S. The gut microbiota and colon cancer. Science 364, 1133–1135 (2019). · DOI
  43. Elinav, E., Garrett, W. S., Trinchieri, G. & Wargo, J. The cancer microbiome. Nat. Rev. Cancer 19, 371–376 (2019). · DOI · Paper page
  44. Zheng, C. et al. Adjuvant treatment and molecular mechanism of probiotic compounds in patients with gastric cancer after gastrectomy. Food Funct 12, 6294–6308 (2021). · DOI
  45. Pan, L. L. et al. Clostridium butyricum strains suppress experimental acute pancreatitis by maintaining intestinal homeostasis. Mol. Nutr. Food Res. 63, e1801419 (2019). · DOI
  46. Amabebe, E., Robert, F. O., Agbalalah, T. & Orubu, E. S. F. Microbial dysbiosis-induced obesity: role of gut microbiota in homoeostasis of energy metabolism. Br. J. Nutr. 123, 1127–1137 (2020). · DOI
  47. Mousa, W. K., Chehadeh, F. & Husband, S. Microbial dysbiosis in the gut drives systemic autoimmune diseases. Front. Immunol. 13, 906258 (2022). · DOI
  48. Sadrekarimi, H. et al. Emerging role of human microbiome in cancer development and response to therapy: special focus on intestinal microflora. J. Transl. Med. 20, 301 (2022). · DOI
  49. Laniewski, P., Ilhan, Z. E. & Herbst-Kralovetz, M. M. The microbiome and gynaecological cancer development, prevention and therapy. Nat Rev Urol 17, 232–250 (2020). · DOI
  50. Zitvogel, L., Ayyoub, M., Routy, B. & Kroemer, G. Microbiome and anticancer immunosurveillance. Cell 165, 276–287 (2016). · DOI · Paper page
  51. Loo, T. M. et al. Gut microbiota promotes obesity-associated liver cancer through PGE(2)-mediated suppression of antitumor immunity. Cancer Discov 7, 522–538 (2017). · DOI · Paper page
  52. Zhang, J. et al. Expansion of colorectal cancer biomarkers based on gut bacteria and viruses. Cancers (Basel) 14, 1–19 (2022).
  53. Yu, X. et al. Gut microbiota changes and its potential relations with thyroid carcinoma. J. Adv. Res. 35, 61–70 (2022). · DOI
  54. Ubachs, J. et al. Gut microbiota and short-chain fatty acid alterations in cachectic cancer patients. J. Cachexia Sarcopenia Muscle 12, 2007–2021 (2021). · DOI · Paper page
  55. Drewes, J. L. et al. Human colon cancer-derived Clostridioides difficile strains drive colonic tumorigenesis in mice. Cancer Discov 12, 1873–1885 (2022). · DOI
  56. Wong, S. H. et al. Gavage of fecal samples from patients with colorectal cancer promotes intestinal carcinogenesis in germ-free and conventional mice. Gastroenterology 153, 1621–1633.e1626 (2017). · DOI · Paper page
  57. Butcher, L. D., den Hartog, G., Ernst, P. B. & Crowe, S. E. Oxidative stress resulting From Helicobacter pylori infection contributes to gastric carcinogenesis. Cell. Mol. Gastroenterol. Hepatol. 3, 316–322 (2017). · DOI
  58. Beil, W. et al. Role of vacA and cagA in Helicobacter pylori inhibition of mucin synthesis in gastric mucous cells. J. Clin. Microbiol. 38, 2215–2218 (2000). · DOI
  59. Guo, S. et al. Exosomes derived from Fusobacterium nucleatum-infected colorectal cancer cells facilitate tumour metastasis by selectively carrying miR-1246/92b-3p/27a-3p and CXCL16. Gut 70, 1507–1519 (2020). · DOI
  60. 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). · DOI · Paper page
  61. Engevik, M. A. et al. Fusobacterium nucleatum secretes outer membrane vesicles and promotes intestinal inflammation. mBio 12, e02706–20 (2021). · DOI
  62. Liu, L., Liang, L., Yang, C., Zhou, Y. & Chen, Y. Extracellular vesicles of Fusobacterium nucleatum compromise intestinal barrier through targeting RIPK1-mediated cell death pathway. Gut Microbes 13, 1–20 (2021). · DOI
  63. Zhang, Y., Zhang, J., Xia, Y. & Sun, J. Bacterial translocation and barrier dysfunction enhance colonic tumorigenesis. Neoplasia 35, 100847 (2022). · DOI
  64. Multhoff, G., Molls, M. & Radons, J. Chronic inflammation in cancer development. Front. Immunol. 2, 98 (2011).
  65. Hui, L. & Chen, Y. Tumor microenvironment: sanctuary of the devil. Cancer Lett 368, 7–13 (2015). · DOI
  66. Lugano, R., Ramachandran, M. & Dimberg, A. Tumor angiogenesis: causes, consequences, challenges and opportunities. Cell. Mol. Life Sci. 77, 1745–1770 (2020). · DOI
  67. Joyce, J. A. & Fearon, D. T. T cell exclusion, immune privilege, and the tumor microenvironment. Science 348, 74–80 (2015). · DOI
  68. Ma, J. et al. The role of the tumor microbe microenvironment in the tumor immune microenvironment: bystander, activator, or inhibitor? J. Exp. Clin. Cancer Res. 40, 327 (2021). · DOI
  69. Vaupel, P. & Harrison, L. Tumor hypoxia: causative factors, compensatory mechanisms, and cellular response. Oncologist 9(Suppl 5), 4–9 (2004). · DOI · Paper page
  70. Milotti, E., Fredrich, T., Chignola, R. & Rieger, H. Oxygen in the tumor microenvironment: mathematical and numerical modeling. Adv. Exp. Med. Biol. 1259, 53–76 (2020). · DOI
  71. Khodaverdi, N., Zeighami, H., Jalilvand, A., Haghi, F. & Hesami, N. High frequency of enterotoxigenic Bacteroides fragilis and Enterococcus faecalis in the paraffin-embedded tissues of Iranian colorectal cancer patients. BMC Cancer 21, 1353 (2021). · DOI
  72. Yuan, Y. Spatial heterogeneity in the tumor microenvironment. Cold Spring Harb. Perspect. Med. 6, a02683 (2016). · DOI · Paper page
  73. Xu, C. et al. Fusobacterium nucleatum promotes colorectal cancer metastasis through miR-1322/CCL20 axis and M2 polarization. Gut Microbes 13, 1980347 (2021). · DOI
  74. Chen, S. et al. Fusobacterium nucleatum promotes colorectal cancer metastasis by modulating KRT7-AS/KRT7. Gut Microbes 11, 511–525 (2020). · DOI
  75. Gao, Y. et al. Fusobacterium nucleatum stimulates cell proliferation and promotes PD-L1 expression via IFIT1-related signal in colorectal cancer. Neoplasia 35, 100850 (2023). · DOI
  76. Mima, K. et al. Fusobacterium nucleatum and T cells in colorectal carcinoma. JAMA Oncol 1, 653–661 (2015). · DOI · Paper page
  77. 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). · DOI
  78. Hamada, T. et al. Fusobacterium nucleatum in colorectal cancer relates to immune response differentially by tumor microsatellite instability status. Cancer Immunol Res 6, 1327–1336 (2018). · DOI
  79. Chmiela, M., Walczak, N. & Rudnicka, K. Helicobacter pylori outer membrane vesicles involvement in the infection development and Helicobacter pylori-related diseases. J. Biomed. Sci. 25, 78 (2018). · DOI
  80. González, M. F., Díaz, P., Sandoval-Bórquez, A., Herrera, D. & Quest, A. F. G. Helicobacter pylori outer membrane vesicles and extracellular vesicles from Helicobacter pylori-Infected cells in gastric disease development. Int. J. Mol. Sci. 22, 4823 (2021). · DOI
  81. Song, X. et al. Microbial metabolite deoxycholic acid promotes vasculogenic mimicry formation in intestinal carcinogenesis. Cancer Sci 113, 459–477 (2022). · DOI
  82. Barrett, M., Hand, C. K., Shanahan, F., Murphy, T. & O’Toole, P. W. Mutagenesis by microbe: the role of the microbiota in shaping the cancer genome. Trends Cancer 6, 277–287 (2020). · DOI · Paper page
  83. Cao, Y. et al. Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites. Science 378, eabm3233 (2022). · DOI
  84. Vizcaino, M. I. & Crawford, J. M. The colibactin warhead crosslinks DNA. Nat. Chem. 7, 411–417 (2015). · DOI · Paper page
  85. 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). · DOI
  86. Toller, I. M. et al. Carcinogenic bacterial pathogen Helicobacter pylori triggers DNA double-strand breaks and a DNA damage response in its host cells. Proc. Natl Acad. Sci. USA. 108, 14944–14949 (2011). · DOI
  87. Valguarnera, E. & Wardenburg, J. B. Good gone bad: one toxin away from disease for Bacteroides fragilis. J. Mol. Biol. 432, 765–785 (2020). · DOI
  88. Martin, O. C. B. et al. Infection with genotoxin-producing Salmonella enterica synergises with loss of the tumour suppressor APC in promoting genomic instability via the PI3K pathway in colonic epithelial cells. Cell. Microbiol. 21, e13099 (2019). · DOI
  89. Azenabor, A. A. & Mahony, J. B. Generation of reactive oxygen species and formation and membrane lipid peroxides in cells infected with Chlamydia trachomatis. Int. J. Infect. Dis. 4, 46–50 (2000). · DOI
  90. Chumduri, C., Gurumurthy, R. K., Zadora, P. K., Mi, Y. & Meyer, T. F. Chlamydia infection promotes host DNA damage and proliferation but impairs the DNA damage response. Cell Host Microbe 13, 746–758 (2013). · DOI
  91. Goodwin, A. C. et al. Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis. Proc. Natl Acad. Sci. USA. 108, 15354–15359 (2011). · DOI · Paper page
  92. Xu, H. et al. Spermine oxidation induced by Helicobacter pylori results in apoptosis and DNA damage: implications for gastric carcinogenesis. Cancer Res 64, 8521–8525 (2004). · DOI
  93. Hartung, M. L. et al. H. pylori-Induced DNA strand breaks are introduced by nucleotide excision repair endonucleases and promote NF-κB target gene expression. Cell Rep 13, 70–79 (2015). · DOI
  94. Tse, J. W. T., Jenkins, L. J., Chionh, F. & Mariadason, J. M. Aberrant DNA methylation in colorectal cancer: what should we target? Trends Cancer 3, 698–712 (2017). · DOI
  95. Xia, X. et al. Bacteria pathogens drive host colonic epithelial cell promoter hypermethylation of tumor suppressor genes in colorectal cancer. Microbiome 8, 108 (2020). · DOI
  96. Ciccia, A. & Elledge, S. J. The DNA damage response: making it safe to play with knives. Mol. Cell 40, 179–204 (2010). · DOI · Paper page
  97. Tubbs, A. & Nussenzweig, A. Endogenous DNA damage as a source of genomic instability in cancer. Cell 168, 644–656 (2017). · DOI · Paper page
  98. Lavin, M. F. ATM and the Mre11 complex combine to recognize and signal DNA double-strand breaks. Oncogene 26, 7749–7758 (2007). · DOI
  99. Kim, J. J. et al. Helicobacter pylori impairs DNA mismatch repair in gastric epithelial cells. Gastroenterology 123, 542–553 (2002). · DOI
  100. Matsumoto, Y. et al. Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium. Nat. Med. 13, 470–476 (2007). · DOI
  101. Li, X. & Heyer, W. D. Homologous recombination in DNA repair and DNA damage tolerance. Cell Res 18, 99–113 (2008). · DOI
  102. Koeppel, M., Garcia-Alcalde, F., Glowinski, F., Schlaermann, P. & Meyer, T. F. Helicobacter pylori infection causes characteristic DNA damage patterns in human cells. Cell Rep 11, 1703–1713 (2015). · DOI
  103. Shibata, A. et al. DNA double-strand break repair pathway choice is directed by distinct MRE11 nuclease activities. Mol. Cell 53, 7–18 (2014). · DOI
  104. Panier, S. & Boulton, S. J. Double-strand break repair: 53BP1 comes into focus. Nat. Rev. Mol. Cell Biol. 15, 7–18 (2014). · DOI
  105. Hanada, K. et al. Helicobacter pylori infection introduces DNA double-strand breaks in host cells. Infect. Immun. 82, 4182–4189 (2014). · DOI
  106. Sishc, B. J. & Davis, A. J. The role of the core non-homologous end joining factors in carcinogenesis and cancer. Cancers (Basel) 9, 1–30 (2017). · DOI
  107. Gaymes, T. J., Mufti, G. J. & Rassool, F. V. Myeloid leukemias have increased activity of the nonhomologous end-joining pathway and concomitant DNA misrepair that is dependent on the Ku70/86 heterodimer. Cancer Res 62, 2791–2797 (2002).
  108. Kastenhuber, E. R. & Lowe, S. W. Putting p53 in context. Cell 170, 1062–1078 (2017). · DOI · Paper page
  109. Hassin, O. & Oren, M. Drugging p53 in cancer: one protein, many targets. Nat. Rev. Drug Discov. 22, 127–144 (2022). · DOI
  110. Clevers, H. Wnt/beta-catenin signaling in development and disease. Cell 127, 469–480 (2006). · DOI · Paper page
  111. Gregorieff, A. & Clevers, H. Wnt signaling in the intestinal epithelium: from endoderm to cancer. Genes Dev 19, 877–890 (2005). · DOI
  112. Yu, F. et al. Wnt/β-catenin signaling in cancers and targeted therapies. Signal Transduct Target Ther 6, 307 (2021). · DOI · Paper page
  113. 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). · DOI
  114. Wu, S., Lim, K. C., Huang, J., Saidi, R. F. & Sears, C. L. Bacteroides fragilis enterotoxin cleaves the zonula adherens protein, E-cadherin. Proc. Natl Acad. Sci. USA. 95, 14979–14984 (1998). · DOI
  115. Fang, J. Y. & Richardson, B. C. The MAPK signalling pathways and colorectal cancer. Lancet Oncol 6, 322–327 (2005). · DOI · Paper page
  116. Mimuro, H. et al. Helicobacter pylori dampens gut epithelial self-renewal by inhibiting apoptosis, a bacterial strategy to enhance colonization of the stomach. Cell Host Microbe 2, 250–263 (2007). · DOI
  117. Nagaraja, V. & Eslick, G. D. Systematic review with meta-analysis: the relationship between chronic Salmonella typhi carrier status and gall-bladder cancer. Aliment. Pharmacol. Ther. 39, 745–750 (2014). · DOI
  118. Kuijl, C. et al. Intracellular bacterial growth is controlled by a kinase network around PKB/AKT1. Nature 450, 725–730 (2007). · DOI
  119. Scanu, T. et al. Salmonella manipulation of host signaling pathways provokes cellular transformation associated with gallbladder carcinoma. Cell Host Microbe 17, 763–774 (2015). · DOI
  120. 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). · DOI · Paper page
  121. Kostic, A. D. et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 14, 207–215 (2013). · DOI · Paper page
  122. Gabrilovich, D. I. Myeloid-derived suppressor cells. Cancer Immunol Res 5, 3–8 (2017). · DOI
  123. Yan, H. H. et al. Gr-1 + CD11b + myeloid cells tip the balance of immune protection to tumor promotion in the premetastatic lung. Cancer Res 70, 6139–6149 (2010). · DOI
  124. Toh, B. et al. Mesenchymal transition and dissemination of cancer cells is driven by myeloid-derived suppressor cells infiltrating the primary tumor. PLoS Biol 9, e1001162 (2011). · DOI
  125. Cui, T. X. et al. Myeloid-derived suppressor cells enhance stemness of cancer cells by inducing microRNA101 and suppressing the corepressor CtBP2. Immunity 39, 611–621 (2013). · DOI
  126. Sakamoto, Y. et al. Relationship between Fusobacterium nucleatum and antitumor immunity in colorectal cancer liver metastasis. Cancer Sci 112, 4470–4477 (2021). · DOI
  127. Zhang, Q. et al. Gut microbiome directs hepatocytes to recruit MDSCs and promote cholangiocarcinoma. Cancer Discov 11, 1248–1267 (2021). · DOI
  128. Holokai, L. et al. Increased programmed death-ligand 1 is an early epithelial cell response to Helicobacter pylori Infection. PLoS Pathog 15, e1007468 (2019). · DOI
  129. Hezaveh, K. et al. Tryptophan-derived microbial metabolites activate the aryl hydrocarbon receptor in tumor-associated macrophages to suppress anti-tumor immunity. Immunity 55, 324–340.e328 (2022). · DOI · Paper page
  130. Rieber, N. et al. Pathogenic fungi regulate immunity by inducing neutrophilic myeloid-derived suppressor cells. Cell Host Microbe 17, 507–514 (2015). · DOI
  131. Sharma, P. C. et al. Recent advances in microbial toxin-related strategies to combat cancer. Semin. Cancer Biol. 86, 753–768 (2022). · DOI
  132. Brynestad, S. & Granum, P. E. Clostridium perfringens and foodborne infections. Int. J. Food Microbiol. 74, 195–202 (2002). · DOI
  133. Kominsky, S. L. et al. Clostridium perfringens enterotoxin elicits rapid and specific cytolysis of breast carcinoma cells mediated through tight junction proteins claudin 3 and 4. Am. J. Pathol. 164, 1627–1633 (2004). · DOI
  134. Romanov, V., Whyard, T. C., Waltzer, W. C. & Gabig, T. G. A claudin 3 and claudin 4-targeted Clostridium perfringens protoxin is selectively cytotoxic to PSA-producing prostate cancer cells. Cancer Lett 351, 260–264 (2014). · DOI
  135. Pahle, J. et al. Rapid eradication of colon carcinoma by Clostridium perfringens Enterotoxin suicidal gene therapy. BMC Cancer 17, 129 (2017). · DOI
  136. Shrestha, A., Uzal, F. A. & McClane, B. A. The interaction of Clostridium perfringens enterotoxin with receptor claudins. Anaerobe 41, 18–26 (2016). · DOI
  137. Mohamed, M. F. et al. Pseudomonas aeruginosa ExoT induces G1 cell cycle arrest in melanoma cells. Cell. Microbiol. 23, e13339 (2021). · DOI
  138. Punj, V. et al. Bacterial cupredoxin azurin as an inducer of apoptosis and regression in human breast cancer. Oncogene 23, 2367–2378 (2004). · DOI
  139. Tan, W. et al. Targeting of pancreatic cancer cells and stromal cells using engineered oncolytic Salmonella typhimurium. Mol. Ther. 30, 662–671 (2022). · DOI
  140. Zhang, Y., Li, Y., Li, H., Chen, W. & Liu, W. Clostridium difficile toxin B recombinant protein inhibits tumor growth and induces apoptosis through inhibiting Bcl-2 expression, triggering inflammatory responses and activating C-erbB-2 and Cox-2 expression in breast cancer mouse model. Biomed. Pharmacother. 101, 391–398 (2018). · DOI
  141. Miyakawa, M., Iijima, S., Kobayashi, R. & Tajima, M. Observation on the Lymphoid Tissue of the Germ-Free Guinea Pig*. Pathol. Int. 7, 183–210 (1957). · DOI
  142. Zhang, Z. et al. Peripheral lymphoid volume expansion and maintenance are controlled by gut microbiota via RALDH + dendritic cells. Immunity 44, 330–342 (2016). · DOI
  143. Bouskra, D. et al. Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature 456, 507–510 (2008). · DOI · Paper page
  144. Yu, L. C. Microbiota dysbiosis and barrier dysfunction in inflammatory bowel disease and colorectal cancers: exploring a common ground hypothesis. J. Biomed. Sci. 25, 79 (2018). · DOI
  145. Tanoue, T. et al. A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Nature 565, 600–605 (2019). · DOI · Paper page
  146. Stewart, O. A., Wu, F. & Chen, Y. The role of gastric microbiota in gastric cancer. Gut Microbes 11, 1220–1230 (2020). · DOI
  147. Yang, L. et al. The relative and attributable risks of cardia and non-cardia gastric cancer associated with Helicobacter pylori infection in China: a case-cohort study. Lancet Public Health 6, e888–e896 (2021). · DOI · Paper page
  148. Martinsen, T. C., Fossmark, R. & Waldum, H. L. The phylogeny and biological function of gastric juice-microbiological consequences of removing gastric acid. Int. J. Mol. Sci. 20, 6031 (2019). · DOI
  149. Mobley, H. L. The role of Helicobacter pylori urease in the pathogenesis of gastritis and peptic ulceration. Aliment. Pharmacol. Ther. 10(Suppl 1), 57–64 (1996). · DOI
  150. Wen, S. & Moss, S. F. Helicobacter pylori virulence factors in gastric carcinogenesis. Cancer Lett 282, 1–8 (2009). · DOI
  151. Ansari, S. & Yamaoka, Y. Helicobacter pylori virulence factor cytotoxin-associated gene A (CagA)-mediated gastric pathogenicity. Int. J. Mol. Sci. 21, 7430 (2020). · DOI
  152. Odenbreit, S. et al. Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science 287, 1497–1500 (2000). · DOI
  153. Butt, J. & Epplein, M. Helicobacter pylori and colorectal cancer-A bacterium going abroad? PLoS Pathog 15, e1007861 (2019). · DOI
  154. Blosse, A. et al. Deregulation of miRNA in Helicobacter pylori-Induced gastric MALT lymphoma: from mice to human. J. Clin. Med. 8, 845 (2019). · DOI
  155. Chen, Y., Shi, T., Li, Y., Huang, L. & Yin, D. Fusobacterium nucleatum: the opportunistic pathogen of periodontal and peri-implant diseases. Front. Microbiol. 13, 860149 (2022). · DOI · Paper page
  156. Castellarin, M. et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res 22, 299–306 (2012). · DOI · Paper page
  157. Kostic, A. D. et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res 22, 292–298 (2012). · DOI · Paper page
  158. Komiya, Y. et al. Patients with colorectal cancer have identical strains of Fusobacterium nucleatum in their colorectal cancer and oral cavity. Gut 68, 1335–1337 (2019). · DOI
  159. 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). · DOI · Paper page
  160. Guo, P. et al. FadA promotes DNA damage and progression of Fusobacterium nucleatum-induced colorectal cancer through up-regulation of chk2. J. Exp. Clin. Cancer Res. 39, 202 (2020). · DOI
  161. Ohkusa, T. et al. Induction of experimental ulcerative colitis by Fusobacterium varium isolated from colonic mucosa of patients with ulcerative colitis. Gut 52, 79–83 (2003). · DOI
  162. 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). · DOI · Paper page
  163. Zamani, S. et al. Enterotoxigenic Bacteroides fragilis: a possible etiological candidate for bacterially-induced colorectal precancerous and cancerous lesions. Front Cell Infect Microbiol 9, 449 (2019). · DOI
  164. Chung, L. et al. Bacteroides fragilis toxin coordinates a pro-carcinogenic inflammatory cascade via targeting of colonic epithelial cells. Cell Host Microbe 23, 203–214.e205 (2018). · DOI
  165. Cao, Y. et al. Enterotoxigenic Bacteroidesfragilis promotes intestinal inflammation and malignancy by inhibiting exosome-packaged miR-149-3p. Gastroenterology 161, 1552–1566.e1512 (2021). · DOI
  166. Zhang, M. et al. miR-149-3p reverses CD8(+) T-cell exhaustion by reducing inhibitory receptors and promoting cytokine secretion in breast cancer cells. Open Biol 9, 190061 (2019). · DOI
  167. Farrell, P. J. Epstein-Barr virus and cancer. Annu. Rev. Pathol. 14, 29–53 (2019). · DOI
  168. Shumilov, A. et al. Epstein-Barr virus particles induce centrosome amplification and chromosomal instability. Nat Commun 8, 14257 (2017). · DOI
  169. Wang, J. et al. EBV miRNAs BART11 and BART17-3p promote immune escape through the enhancer-mediated transcription of PD-L1. Nat Commun 13, 866 (2022). · DOI · Paper page
  170. Duan, X. et al. EBV infection in epithelial malignancies induces resistance to antitumor natural killer cells via F3-mediated platelet aggregation. Cancer Res 82, 1070–1083 (2022). · DOI
  171. Chou, Y. C., Ho, P. Y., Chen, W. J., Wu, S. H. & Pan, M. H. Lactobacillus fermentum V3 ameliorates colitis-associated tumorigenesis by modulating the gut microbiome. Am. J. Cancer Res. 10, 1170–1181 (2020).
  172. Si, W. et al. Lactobacillus rhamnosus GG induces cGAS/STING- dependent type I interferon and improves response to immune checkpoint blockade. Gut 71, 521–533 (2022). · DOI
  173. Zhang, S. L. et al. Lacticaseibacillus paracasei sh2020 induced antitumor immunity and synergized with anti-programmed cell death 1 to reduce tumor burden in mice. Gut Microbes 14, 2046246 (2022). · DOI
  174. Wu, H. et al. Lactobacillus reuteri maintains intestinal epithelial regeneration and repairs damaged intestinal mucosa. Gut Microbes 11, 997–1014 (2020). · DOI
  175. Schroeder, B. O. et al. Bifidobacteria or fiber protects against diet-induced microbiota-mediated colonic mucus deterioration. Cell Host Microbe 23, 27–40.e27 (2018). · DOI · Paper page
  176. 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). · DOI
  177. Li, Q. et al. Streptococcus thermophilus inhibits colorectal tumorigenesis through secreting beta-galactosidase. Gastroenterology 160, 1179–1193.e1114 (2021). · DOI
  178. Singh, R. et al. Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway. Nat Commun 10, 89 (2019). · DOI · Paper page
  179. Konings, E. J. et al. Folate intake of the Dutch population according to newly established liquid chromatography data for foods. Am. J. Clin. Nutr. 73, 765–776 (2001). · DOI
  180. Wasilewska, E., Zlotkowska, D. & Wroblewska, B. Yogurt starter cultures of Streptococcus thermophilus and Lactobacillus bulgaricus ameliorate symptoms and modulate the immune response in a mouse model of dextran sulfate sodium-induced colitis. J. Dairy Sci. 102, 37–53 (2019). · DOI
  181. Sakanaka, A. et al. Fusobacterium nucleatum metabolically integrates commensals and pathogens in oral biofilms. mSystems 7, e0017022 (2022). · DOI
  182. Shirasawa, Y., Shibahara-Sone, H., Iino, T. & Ishikawa, F. Bifidobacterium bifidum BF-1 suppresses Helicobacter pylori-induced genes in human epithelial cells. J. Dairy Sci. 93, 4526–4534 (2010). · DOI
  183. Maubach, G., Vieth, M., Boccellato, F. & Naumann, M. Helicobacter pylori-induced NF-κB: trailblazer for gastric pathophysiology. Trends Mol. Med. 28, 210–222 (2022). · DOI
  184. Chattopadhyay, I., Nandi, D. & Nag, A. The pint- sized powerhouse: Illuminating the mighty role of the gut microbiome in improving the outcome of anti- cancer therapy. Semin. Cancer Biol. 70, 98–111 (2021). · DOI
  185. Zhang, M., Li, R. W., Yang, H., Tan, Z. & Liu, F. Recent advances in developing butyrogenic functional foods to promote gut health. Crit. Rev. Food Sci. Nutr. 62, 1–22 (2022). · DOI
  186. Liu, H. et al. Butyrate: A Double-Edged Sword for Health? Adv. Nutr. 9, 21–29 (2018). · DOI
  187. Peng, L., Li, Z. R., Green, R. S., Holzman, I. R. & Lin, J. Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J. Nutr. 139, 1619–1625 (2009). · DOI · Paper page
  188. Willemsen, L. E., Koetsier, M. A., van Deventer, S. J. & van Tol, E. A. Short chain fatty acids stimulate epithelial mucin 2 expression through differential effects on prostaglandin E(1) and E(2) production by intestinal myofibroblasts. Gut 52, 1442–1447 (2003). · DOI
  189. Li, Q. et al. Butyrate suppresses the proliferation of colorectal cancer cells via targeting pyruvate kinase M2 and metabolic reprogramming. Mol. Cell. Proteomics 17, 1531–1545 (2018). · DOI
  190. Dmitrieva-Posocco, O. et al. β-Hydroxybutyrate suppresses colorectal cancer. Nature 605, 160–165 (2022). · DOI
  191. Li, Y., He, P., Liu, Y., Qi, M. & Dong, W. Combining sodium butyrate with cisplatin increases the apoptosis of gastric cancer in vivo and in vitro via the mitochondrial apoptosis pathway. Front. Pharmacol. 12, 708093 (2021). · DOI
  192. Ridlon, J. M. et al. The ‘in vivo lifestyle’ of bile acid 7alpha-dehydroxylating bacteria: comparative genomics, metatranscriptomic, and bile acid metabolomics analysis of a defined microbial community in gnotobiotic mice. Gut Microbes 11, 381–404 (2020). · DOI
  193. Ridlon, J. M., Wolf, P. G. & Gaskins, H. R. Taurocholic acid metabolism by gut microbes and colon cancer. Gut Microbes 7, 201–215 (2016). · DOI · Paper page
  194. Fu, T. et al. FXR regulates intestinal cancer stem. Cell Proliferation. Cell 176, 1098–1112.e1018 (2019).
  195. Song, X. et al. Microbial bile acid metabolites modulate gut RORgamma(+) regulatory T cell homeostasis. Nature 577, 410–415 (2020). · DOI · Paper page
  196. Lin, R. et al. Deoxycholic acid modulates the progression of gallbladder cancer through N(6)-methyladenosine-dependent microRNA maturation. Oncogene 39, 4983–5000 (2020). · DOI
  197. Wyatt, M. & Greathouse, K. L. Targeting dietary and microbial tryptophan-indole metabolism as therapeutic approaches to colon cancer. Nutrients 13, 1189 (2021). · DOI
  198. Venkateswaran, N. et al. MYC promotes tryptophan uptake and metabolism by the kynurenine pathway in colon cancer. Genes Dev 33, 1236–1251 (2019). · DOI
  199. Xu, R., Wang, Q. & Li, L. A genome-wide systems analysis reveals strong link between colorectal cancer and trimethylamine N-oxide (TMAO), a gut microbial metabolite of dietary meat and fat. BMC Genomics 16(Suppl 7), S4 (2015). · DOI · Paper page
  200. Wang, Z. et al. Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell 163, 1585–1595 (2015). · DOI · Paper page

200 of 340 shown

Metadata

Authors
Zhao, L.-Y., Mei, J.-X., Yu, G., Lei, L., Zhang, W.-H., Liu, K., Chen, X.-L., Kołat, D., Yang, K., & Hu, J.-K.
Affiliations
  • Sichuan University (CN)
  • Medical University of Lodz (PL)
Corresponding author
  • Yang, Kun
  • Hu, Jian-Kun
ORCID
Venue
Signal Transduction and Targeted Therapy
Publisher
Springer Science and Business Media LLC
Published
2023-05-13
Volume
8
Issue
1
Pages
201-201
ISSN
2059-3635 (ISSN-L)
DOI
10.1038/s41392-023-01406-7
PMC
PMC10183032
OpenAlex
W4376641871
Cited by
359
References
426
Citations by year
2026: 83 · 2025: 160 · 2024: 100 · 2023: 16
FWCI
9.48
Type
journal article
Language
en
Open access
Licence
Locations
  • Signal Transduction and Targeted Therapy (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (82072688)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Bacterial Cancer Therapy
Keywords
gut microbiota, cancer, cancer therapy, immunotherapy, chemotherapy, radiotherapy, cancer surgery, precision oncology, treatment response
MeSH terms
Gastrointestinal Microbiome, Antineoplastic Agents, Humans, Immunotherapy, Neoplasms, Microbiota

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review