Skip to main content

Microbiota in cancer development and treatment

Abstract

Purpose

Human microbiota comprises of a variety of organisms ranging from bacterial species to viruses, fungi, and protozoa which are present on the epidermal and mucosal barriers of the body. It plays a key role in health and survival of the host by regulation of the systemic functions. Its apparent functions in modulation of the host immune system, inducing carcinogenesis and regulation of the response to the cancer therapy through a variety of mechanisms such as bacterial dysbiosis, production of genotoxins, pathobionts, and disruption of the host metabolism are increasingly becoming evident.

Methods

Different electronic databases such as PubMed, Google Scholar, and Web of Science were searched for relevant literature which has been reviewed in this article.

Results

Characterization of the microbiome particularly gut microbiota, understanding of the host–microbiota interactions, and its potential for therapeutic exploitation are necessary for the development of novel anticancer therapeutic strategies with better efficacy and lowered off-target side effects.

Conclusion

In this review, the role of microbiota is explained in carcinogenesis, mechanisms of microbiota-mediated carcinogenesis, and role of gut microbiota in modulation of cancer therapy.

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

Fig. 1
Fig. 2

References

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Alam B, Saporoschetz I, Epstein S (1971) Synthesis of nitrosopiperidine from nitrate and piperidine in the gastro-intestinal tract of the rat. Nature 232:199

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  4. Al-Mayah A et al (2015) The non-targeted effects of radiation are perpetuated by exosomes. Mutat Res Fundam Mol Mech Mutagen 772:38–45

    Article  CAS  Google Scholar 

  5. Apostolou P, Tsantsaridou A, Papasotiriou I, Toloudi M, Chatziioannou M, Giamouzis G (2011) Bacterial and fungal microflora in surgically removed lung cancer samples. J Cardiothorac Surg 6:137

    Article  PubMed  PubMed Central  Google Scholar 

  6. Arthur JC et al (2012) Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 338:120–123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Attene-Ramos MS, Wagner ED, Plewa MJ, Gaskins HR (2006) Evidence that hydrogen sulfide is a genotoxic agent. Mol Cancer Res 4:9–14

    Article  CAS  PubMed  Google Scholar 

  8. Baek MK et al (2010) Lithocholic acid upregulates uPAR and cell invasiveness via MAPK and AP-1 signaling in colon cancer cells. Cancer Lett 290:123–128

    Article  CAS  PubMed  Google Scholar 

  9. Barker HE, Paget JT, Khan AA, Harrington KJ (2015) The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence. Nat Rev Cancer 15:409

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bayerdörffer E et al (1995) Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection. Lancet 345:1591–1594

    Article  PubMed  Google Scholar 

  11. Belcheva A et al (2014) Gut microbial metabolism drives transformation of MSH2-deficient colon epithelial cells. Cell 158:288–299

    Article  CAS  PubMed  Google Scholar 

  12. Belkaid Y, Hand TW (2014) Role of the microbiota in immunity and inflammation. Cell 157:121–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Belkaid Y, Naik S (2013) Compartmentalized and systemic control of tissue immunity by commensals. Nat Immunol 14:646–653

    Article  CAS  PubMed  Google Scholar 

  14. Bernstein C, Holubec H, Bhattacharyya AK, Nguyen H, Payne CM, Zaitlin B, Bernstein H (2011) Carcinogenicity of deoxycholate, a secondary bile acid. Arch Toxicol 85:863–871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bindels LB et al (2012) Gut microbiota-derived propionate reduces cancer cell proliferation in the liver. Br J Cancer 107:1337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Boleij A et al (2014) The Bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients. Clin Infect Dis 60:208–215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bonnet M et al (2014) Colonization of the human gut by E. coli and colorectal cancer risk. Clin Cancer Res 20:859–867

    Article  PubMed  Google Scholar 

  18. Boulangé CL, Neves AL, Chilloux J, Nicholson JK, Dumas M-E (2016) Impact of the gut microbiota on inflammation, obesity, and metabolic disease. Genome Med 8:42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Broin P et al (2015) Intestinal microbiota-derived metabolomic blood plasma markers for prior radiation injury. Int J Radiat Oncol Biol Phys 91:360–367

    Article  PubMed Central  Google Scholar 

  20. Carbone C et al (2018) Angiopoietin-like proteins in angiogenesis inflammation and cancer. Int J Mol Sci 19:431

    Article  CAS  PubMed Central  Google Scholar 

  21. Carbonero F, Benefiel AC, Alizadeh-Ghamsari AH, Gaskins HR (2012) Microbial pathways in colonic sulfur metabolism and links with health and disease. Front Physiol 3:448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Caygill CP, Hill MJ, Braddick M, Sharp JC (1994) Cancer mortality in chronic typhoid and paratyphoid carriers. Lancet 343:83–84

    Article  CAS  PubMed  Google Scholar 

  24. Chan PJ, Seraj IM, Kalugdan TH, King A (1996) Prevalence of mycoplasma conserved DNA in malignant ovarian cancer detected using sensitive PCR-ELISA. Gynecol Oncol 63:258–260

    Article  CAS  PubMed  Google Scholar 

  25. Chang MC, Keasling JD (2006) Production of isoprenoid pharmaceuticals by engineered microbes. Nat Chem Biol 2:674–681

    Article  CAS  PubMed  Google Scholar 

  26. Chanudet E et al (2007) Chlamydiae and Mycoplasma infections in pulmonary MALT lymphoma. Br J Cancer 97:949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Chaput N et al (2017) Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. Ann Oncol 28:1368–1379

    Article  CAS  PubMed  Google Scholar 

  28. Chen GY, Shaw MH, Redondo G, Núñez G (2008) The innate immune receptor Nod1 protects the intestine from inflammation-induced tumorigenesis. Cancer Res 68:10060–10067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Chen W, Liu F, Ling Z, Tong X, Xiang C (2012) Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer. PLoS One 7:e39743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Cho JH (2008) The genetics and immunopathogenesis of inflammatory bowel disease. Nat Rev Immunol 8:458

    Article  CAS  Google Scholar 

  31. Clarke G, Stilling RM, Kennedy PJ, Stanton C, Cryan JF, Dinan TG (2014) Minireview: Gut microbiota: the neglected endocrine organ. Mol Endocrinol 28:1221–1238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Cong J, Zhang X (2018) How human microbiome talks to health and disease. Eur J Clin Microbiol Infect Dis 37:1595–1601

    Article  PubMed  Google Scholar 

  33. Consortium HMP (2012) Structure, function and diversity of the healthy human microbiome. Nature 486:207–214

    Article  CAS  Google Scholar 

  34. Cotillard A et al (2013) Dietary intervention impact on gut microbial gene richness. Nature 500:585

    Article  CAS  PubMed  Google Scholar 

  35. Couturier-Maillard A et al (2013) NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer. J Clin Investig 123(2):700–711

    CAS  Google Scholar 

  36. Cuevas-Ramos G, Petit CR, Marcq I, Boury M, Oswald E, Nougayrède J-P (2010) Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells. Proc Natl Acad Sci 107:11537–11542

    Article  PubMed  Google Scholar 

  37. Dapito DH et al (2012) Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4. Cancer Cell 21:504–516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. De Martel C, Plummer M, Parsonnet J, Van Doorn L, Franceschi S (2009) Helicobacter species in cancers of the gallbladder and extrahepatic biliary tract. Br J Cancer 100:194

    Article  CAS  PubMed  Google Scholar 

  39. Devkota S et al (2012) Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10–/– mice. Nature 487:104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. DeWeerdt S (2011) Food: the omnivore’s labyrinth. Nature 471:S22–S24

    Article  CAS  PubMed  Google Scholar 

  41. Dong L, Li J, Liu Y, Yue W, Luo X (2012) Toll‐like receptor 2 monoclonal antibody or/and Toll‐like receptor 4 monoclonal antibody increase counts of Lactobacilli and Bifidobacteria in dextran sulfate sodium‐induced colitis in mice. J Gastroenterol Hepatol 27:110–119

    Article  CAS  PubMed  Google Scholar 

  42. Donohoe DR, Garge N, Zhang X, Sun W, O’Connell TM, Bunger MK, Bultman SJ (2011) The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab 13:517–526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Dutton RJ, Turnbaugh PJ (2012) Taking a metagenomic view of human nutrition. Curr Opin Clin Nutr Metab Care 15:448–454

    Article  PubMed  Google Scholar 

  44. Dzutsev A, Goldszmid RS, Viaud S, Zitvogel L, Trinchieri G (2015) The role of the microbiota in inflammation, carcinogenesis, and cancer therapy. Eur J Immunol 45:17–31

    Article  CAS  PubMed  Google Scholar 

  45. Elinav E, Strowig T, Henao-Mejia J, Flavell RA (2011) Regulation of the antimicrobial response by NLR proteins. Immunity 34:665–679

    Article  CAS  PubMed  Google Scholar 

  46. Epplein M, Pawlita M, Michel A, Peek RM, Cai Q, Blot WJ (2013) Helicobacter pylori protein—specific antibodies and risk of colorectal cancer. Cancer Epidemiol Prev Biomark 22(11):1964–1974

    Article  CAS  Google Scholar 

  47. Faith JJ et al (2013) The long-term stability of the human gut microbiota. Science 341:1237439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Feng R et al (2015) Transforming berberine into its intestine-absorbable form by the gut microbiota. Sci Rep 5:12155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ferreri AJ et al (2012) Chlamydophila psittaci eradication with doxycycline as first-line targeted therapy for ocular adnexae lymphoma: final results of an international phase II trial. J Clin Oncol 30:2988–2994

    Article  CAS  PubMed  Google Scholar 

  50. Fox JG, Wang TC (2007) Inflammation, atrophy, and gastric cancer. J Clin Investig 117:60–69

    Article  CAS  PubMed  Google Scholar 

  51. Fox JG et al (2004) Gastroenteritis in NF-κB-deficient mice is produced with wild-type Camplyobacter jejuni but not with C. jejuni lacking cytolethal distending toxin despite persistent colonization with both strains. Infect Immun 72:1116–1125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Frankel AE, Coughlin LA, Kim J, Froehlich TW, Xie Y, Frenkel EP, Koh AY (2017) Metagenomic shotgun sequencing and unbiased metabolomic profiling identify specific human gut microbiota and metabolites associated with immune checkpoint therapy efficacy in melanoma patients. Neoplasia 19:848–855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Fukata M et al (2007) Toll-like receptor-4 promotes the development of colitis-associated colorectal tumors. Gastroenterology 133:1869–1869.e1814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Fukata M et al (2010) Constitutive activation of epithelial TLR4 augments inflammatory responses to mucosal injury and drives colitis-associated tumorigenesis. Inflamm Bowel Dis 17:1464–1473

    Article  PubMed  PubMed Central  Google Scholar 

  55. Gagnière J et al (2016) Gut microbiota imbalance and colorectal cancer. World J Gastroenterol 22:501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Gamallat Y et al (2016) Lactobacillus rhamnosus induced epithelial cell apoptosis, ameliorates inflammation and prevents colon cancer development in an animal model. Biomed Pharmacother 83:536–541

    Article  CAS  Google Scholar 

  57. Garaude J, Kent A, van Rooijen N, Blander JM (2012) Simultaneous targeting of toll-and nod-like receptors induces effective tumor-specific immune responses. Sci Transl Med 4:120ra116

    Article  CAS  Google Scholar 

  58. Garrett WS (2015) Cancer the microbiota. Science 348:80–86

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Garrett WS et al (2010) Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. Cell Host Microbe 8:292–300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Gill SR et al (2006) Metagenomic analysis of the human distal gut microbiome. Science 312:1355–1359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  62. Goubet A-G, Daillère R, Routy B, Derosa L, Roberti PM, Zitvogel L (2018) The impact of the intestinal microbiota in therapeutic responses against cancer. Comptes rendus biologies 341(5):284–289

    Article  PubMed  Google Scholar 

  63. Grivennikov SI et al (2012) Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 491:254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Grootaert C et al (2011) Bacterial monocultures, propionate, butyrate and H2O2 modulate the expression, secretion and structure of the fasting-induced adipose factor in gut epithelial cell lines. Environ microbiol 13:1778–1789

    Article  CAS  PubMed  Google Scholar 

  65. Ha Y-H, Park D-G (2010) Effects of DCA on cell cycle proteins in colonocytes. J Korean Soc Coloproctol 26:254–259

    Article  PubMed  PubMed Central  Google Scholar 

  66. Haiser HJ, Turnbaugh PJ (2012) Is it time for a metagenomic basis of therapeutics? Science 336:1253–1255

    Article  CAS  PubMed  Google Scholar 

  67. Haiser HJ, Turnbaugh PJ (2013) Developing a metagenomic view of xenobiotic metabolism. Pharmacol Res 69:21–31

    Article  CAS  PubMed  Google Scholar 

  68. Hajishengallis G, Darveau RP, Curtis MA (2012) The keystone-pathogen hypothesis. Nat Rev Microbiol 10:717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Hold GL, Smith M, Grange C, Watt ER, El-Omar EM, Mukhopadhya I (2014) Role of the gut microbiota in inflammatory bowel disease pathogenesis: what have we learnt in the past 10 years? World J Gastroenterol WJG 20:1192

    Article  PubMed  Google Scholar 

  71. Holmes E, Li JV, Marchesi JR, Nicholson JK (2012) Gut microbiota composition and activity in relation to host metabolic phenotype and disease risk. Cell Metab 16:559–564

    Article  CAS  Google Scholar 

  72. Hooper SJ, Crean S-J, Fardy MJ, Lewis MA, Spratt DA, Wade WG, Wilson MJ (2007) A molecular analysis of the bacteria present within oral squamous cell carcinoma. J Med Microbiol 56:1651–1659

    Article  CAS  PubMed  Google Scholar 

  73. Hou J, Zheng H, Li P, Liu H, Zhou H, Yang X (2018) Distinct shifts in the oral microbiota are associated with the progression and aggravation of mucositis during radiotherapy. Radiother Oncol 129(1):44–51

    Article  PubMed  Google Scholar 

  74. Hu S, Dong TS, Dalal SR, Wu F, Bissonnette M, Kwon JH, Chang EB (2011) The microbe-derived short chain fatty acid butyrate targets miRNA-dependent p21 gene expression in human colon cancer. PLoS One 6:e16221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Hu B et al (2013) Microbiota-induced activation of epithelial IL-6 signaling links inflammasome-driven inflammation with transmissible cancer. Proc Natl Acad Sci 110:9862–9867

    Article  PubMed  Google Scholar 

  76. Hu B et al (2016) The DNA-sensing AIM2 inflammasome controls radiation-induced cell death tissue injury. Science 354:765–768

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Huttenhower C et al (2012) Structure, function and diversity of the healthy human microbiome. Nature 486:207

    Article  CAS  Google Scholar 

  78. Huycke MM, Gaskins HR (2004) Commensal bacteria, redox stress, and colorectal cancer: mechanisms and models. Exp Biol Med 229:586–597

    Article  CAS  Google Scholar 

  79. Iida N et al (2013) Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 342:967–970

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  81. Jones RM et al (2015) Lactobacilli modulate epithelial cytoprotection through the Nrf2 pathway. Cell Rep 12:1217–1225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Khor B, Gardet A, Xavier RJ (2011) Genetics and pathogenesis of inflammatory bowel disease. Nature 474:307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Klimesova K et al (2013) Altered gut microbiota promotes colitis-associated cancer in IL-1 receptor-associated kinase M deficient mice. Inflamm Bowel Dis 19:1266

    Article  PubMed  PubMed Central  Google Scholar 

  84. Kobayashi KS, Chamaillard M, Ogura Y, Henegariu O, Inohara N, Nunez G, Flavell RA (2005) Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307:731–734

    Article  CAS  PubMed  Google Scholar 

  85. Kostic AD et al (2012) Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res 22:292–298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Kroemer G, Galluzzi L, Kepp O, Zitvogel L (2013) Immunogenic cell death in cancer therapy. Annu Rev Immunol 31:51–72

    Article  CAS  Google Scholar 

  88. Le Chatelier E et al (2013) Richness of human gut microbiome correlates with metabolic markers. Nature 500:541

    Article  CAS  Google Scholar 

  89. Lecuit M et al (2004) Immunoproliferative small intestinal disease associated with Campylobacter jejuni New England. J Med 350:239–248

    CAS  Google Scholar 

  90. Lehouritis P et al (2015) Local bacteria affect the efficacy of chemotherapeutic drugs. Sci Rep 5:14554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Lofgren JL et al (2011) Lack of commensal flora in Helicobacter pylori-infected INS-GAS mice reduces gastritis and delays intraepithelial neoplasia. Gastroenterology 140:210–220.e214

    Article  PubMed  Google Scholar 

  92. Louis P, Hold GL, Flint HJ (2014a) The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev Microbiol 12:661–672

    Article  CAS  PubMed  Google Scholar 

  93. Louis P, Hold GL, Flint HJ (2014b) The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev Microbiol 12:661

    Article  CAS  PubMed  Google Scholar 

  94. Lupp C, Robertson ML, Wickham ME, Sekirov I, Champion OL, Gaynor EC, Finlay BB (2007) Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriaceae. Cell Host Microbe 2:119–129

    Article  CAS  Google Scholar 

  95. Mabrok HB, Klopfleisch R, Ghanem KZ, Clavel T, Blaut M, Loh G (2011) Lignan transformation by gut bacteria lowers tumor burden in a gnotobiotic rat model of breast cancer. Carcinogenesis 33:203–208

    Article  CAS  PubMed  Google Scholar 

  96. Matson V et al (2018) The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 359:104–108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Mavragani IV, Laskaratou DA, Frey B, Candéias SM, Gaipl US, Lumniczky K, Georgakilas AG (2016) Key mechanisms involved in ionizing radiation-induced systemic effects. A current review. Toxicol Res 5:12–33

    Article  Google Scholar 

  98. McGovern DP et al (2005) Association between a complex insertion/deletion polymorphism in NOD1 (CARD4) and susceptibility to inflammatory bowel disease. Hum Mol Genet 14:1245–1250

    Article  CAS  Google Scholar 

  99. Mima K et al (2015) Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis. Gut 341(5):284–289

    Google Scholar 

  100. Minemura M, Shimizu Y (2015) Gut microbiota and liver diseases. World J Gastroenterol WJG 21:1691

    Article  CAS  PubMed  Google Scholar 

  101. Mitchell EP (2006) Gastrointestinal toxicity of chemotherapeutic agents. Semin Oncol 33(1):106–120

    Article  CAS  PubMed  Google Scholar 

  102. Mittal D, Saccheri F, Vénéreau E, Pusterla T, Bianchi ME, Rescigno M (2010) TLR4-mediated skin carcinogenesis is dependent on immune and radioresistant cells. EMBO J 29:2242–2252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Moresco EMY, LaVine D, Beutler B (2011) Toll-like receptors. Curr Biol 21:R488–R493

    Article  CAS  PubMed  Google Scholar 

  104. Morgan XC et al (2012) Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol 13:R79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Nath G, Singh H, Shukla V (1997) Chronic typhoid carriage and carcinoma of the gallbladder. Eur J Cancer Prev 6:557–559

    Article  CAS  PubMed  Google Scholar 

  106. Nešić D, Hsu Y, Stebbins CE (2004) Assembly and function of a bacterial genotoxin. Nature 429:429

    Article  CAS  PubMed  Google Scholar 

  107. Neufert C et al (2013) Tumor fibroblast-derived epiregulin promotes growth of colitis-associated neoplasms through ERK. J Clin Investig 123:1428–1443

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  109. Nyangale EP, Mottram DS, Gibson GR (2012) Gut microbial activity, implications for health and disease: the potential role of metabolite analysis. J Proteome Res 11:5573–5585

    Article  CAS  PubMed  Google Scholar 

  110. Ochi A et al (2012) MyD88 inhibition amplifies dendritic cell capacity to promote pancreatic carcinogenesis via Th2 cells. J Exp Med 209:1671–1687

    Article  PubMed  PubMed Central  Google Scholar 

  111. Ohnishi N et al (2008) Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. Proc Natl Acad Sci 105:1003–1008

    Article  PubMed  Google Scholar 

  112. Pateras IS et al (2015) The DNA damage response and immune signaling alliance: is it good or bad? Nature decides when where. Pharmacol Ther 154:36–56

    Article  CAS  PubMed  Google Scholar 

  113. Patwa LG, Fan TJ, Tchaptchet S, Liu Y, Lussier YA, Sartor RB, Hansen JJ (2011) Chronic intestinal inflammation induces stress-response genes in commensal. Escherichia coli. Gastroenterology 141:1842–1851.e1810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Perez-Chanona E, Trinchieri G (2016) The role of microbiota in cancer therapy. Curr Opin Immunol 39:75–81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Petnicki-Ocwieja T, Hrncir T, Liu Y-J, Biswas A, Hudcovic T, Tlaskalova-Hogenova H, Kobayashi KS (2009) Nod2 is required for the regulation of commensal microbiota in the intestine. Proc Natl Acad Sci 106:15813–15818

    Article  PubMed  Google Scholar 

  116. Philipp B (2011) Bacterial degradation of bile salts. Appl Microbiol Biotechnol 89:903–915

    Article  CAS  PubMed  Google Scholar 

  117. Plottel CS, Blaser MJ (2011) Microbiome malignancy. Cell Host Microbe 10:324–335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Pradere J-P, Dapito DH, Schwabe RF (2014) The Yin and Yang of toll-like receptors in cancer. Oncogene 33:3485–3495

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Quante M et al (2012) Bile acid and inflammation activate gastric cardia stem cells in a mouse model of Barrett-like metaplasia. Cancer Cell 21:36–51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Quigley EM (2013) Gut bacteria in health and disease. Gastroenterol Hepatol 9:560

    Google Scholar 

  122. Raza MH, Siraj S, Arshad A, Waheed U, Aldakheel F, Alduraywish S, Arshad M (2017) ROS-modulated therapeutic approaches in cancer treatment. J Cancer Res Clin Oncol 143:1789–1809

    Article  CAS  PubMed  Google Scholar 

  123. Robert C et al (2011) Ipilimumab plus dacarbazine for previously untreated metastatic melanoma New England. J Med 364:2517–2526

    CAS  Google Scholar 

  124. Routy B et al (2017) The influence of gut-decontamination prophylactic antibiotics on acute graft-versus-host disease and survival following allogeneic hematopoietic stem cell transplantation. OncoImmunology 6:e1258506

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  126. Roy S, Trinchieri G (2017) Microbiota: a key orchestrator of cancer therapy. Nat Rev Cancer 17(5):271–285

    Article  CAS  PubMed  Google Scholar 

  127. Rubinstein MR, Wang X, Liu W, Hao Y, Cai G, Han YW (2013) Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin. Cell Host Microbe 14:195–206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Russell WR et al (2011) High-protein, reduced-carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health. Am J Clin Nutr 93:1062–1072

    Article  CAS  PubMed  Google Scholar 

  129. Salcedo R et al (2010) MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18. J Exp Med 207(8):1625–1636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Samet A, Śledzińska A, Krawczyk B, Hellmann A, Nowicki S, Kur J, Nowicki B (2013) Leukemia and risk of recurrent Escherichia coli bacteremia: genotyping implicates E. coli translocation from the colon to the bloodstream. Eur J Clin Microbiol Infect Dis 32:1393–1400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Sanapareddy N et al (2012) Increased rectal microbial richness is associated with the presence of colorectal adenomas in humans. ISME J 6:1858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Sancho-Martínez SM, Prieto-García L, Prieto M, López-Novoa JM, López-Hernández FJ (2012) Subcellular targets of cisplatin cytotoxicity: an integrated view. Pharmacol Ther 136:35–55

    Article  CAS  PubMed  Google Scholar 

  133. Sartor RB, Mazmanian SK (2012) Intestinal microbes in inflammatory bowel diseases. Am J Gastroenterol Suppl 1:15–21

    Article  CAS  Google Scholar 

  134. Schiavoni G et al (2010) Cyclophosphamide synergizes with type I interferons through systemic dendritic cell reactivation and induction of immunogenic tumor apoptosis. Cancer Res (canres.2788.2010)

  135. Schwabe RF, Jobin C (2013a) The microbiome and cancer. Nat Rev Cancer 13:800–812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Sears CL, Myers LL, Lazenby A, Van Tassell RL (1995) Enterotoxigenic Bacteroides fragilis. Clin Infect Dis 20:S142–S148

    Article  PubMed  Google Scholar 

  137. Seitz HK, Stickel F (2007) Molecular mechanisms of alcohol-mediated carcinogenesis. Nat Rev Cancer 7:599

    Article  CAS  PubMed  Google Scholar 

  138. Selwyn FP, Cui JY, Klaassen CD (2015) RNA-Seq quantification of hepatic drug processing genes in germ-free mice. Drug Metab Dispos 43:1572–1580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Senff NJ et al (2008) European organization for research and treatment of cancer and international society for Cutaneous Lymphoma consensus recommendations for the management of cutaneous B-cell lymphomas. Blood 112:1600–1609

    Article  CAS  PubMed  Google Scholar 

  140. Shanmughapriya S, Senthilkumar G, Vinodhini K, Das B, Vasanthi N, Natarajaseenivasan K (2012) Viral and bacterial aetiologies of epithelial ovarian cancer. Eur J Clin Microbiol Infect Dis 31:2311–2317

    Article  CAS  PubMed  Google Scholar 

  141. Sharma P, Allison JP (2015) The future of immune checkpoint therapy. Science 348:56–61

    Article  CAS  Google Scholar 

  142. Shen S, Wong CH (2016) Bugging inflammation: role of the gut microbiota. Clin Transl Immunol 5:e72

    Article  CAS  Google Scholar 

  143. Shen Z et al (2009) Cytolethal distending toxin promotes Helicobacter cinaedi-associated typhlocolitis in interleukin-10-deficient mice. Infect Immun 77:2508–2516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Sivan A et al (2015) Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350(6264):1084–1089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Smith JL, Bayles DO (2006) The contribution of cytolethal distending toxin to bacterial pathogenesis. Crit Rev Microbiol 32:227–248

    Article  CAS  PubMed  Google Scholar 

  146. Sobhani I et al (2011) Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS One 6:e16393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Stecher B et al (2012) Gut inflammation can boost horizontal gene transfer between pathogenic and commensal Enterobacteriaceae. Proc Natl Acad Sci 109:1269–1274

    Article  PubMed  Google Scholar 

  148. Taieb F, Petit C, Nougayrède J-P, Oswald E (2016) The enterobacterial genotoxins: cytolethal distending toxin and colibactin. EcoSal Plus. https://doi.org/10.1128/ecosalplus.ESP-0008-2016

    Article  PubMed  Google Scholar 

  149. Takemura N, Uematsu S (2017) Blockade of Tlr3 protects mice from lethal radiation-induced gastrointestinal syndrome: Tu-p6-9. Cytokine 100:152

    Google Scholar 

  150. Takemura N et al (2014) Blockade of TLR3 protects mice from lethal radiation-induced gastrointestinal syndrome. Nat Commun 5:3492

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Touchefeu Y et al (2014) Systematic review: the role of the gut microbiota in chemotherapy-or radiation-induced gastrointestinal mucositis—current evidence and potential clinical applications. Aliment Pharmacol Ther 40:409–421

    CAS  PubMed  Google Scholar 

  152. Travaglione S, Fabbri A, Fiorentini C (2008) The Rho-activating CNF1 toxin from pathogenic E. coli: a risk factor for human cancer development? Infect Agents Cancer 3:4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Tye H et al (2012) STAT3-driven upregulation of TLR2 promotes gastric tumorigenesis independent of tumor inflammation. Cancer Cell 22:466–478

    Article  CAS  PubMed  Google Scholar 

  154. Vacchelli E et al (2013) Trial watch: anticancer radioimmunotherapy. Oncoimmunology 2:e25595

    Article  PubMed  PubMed Central  Google Scholar 

  155. Van Duynhoven J et al (2011) Metabolic fate of polyphenols in the human superorganism. Proc Natl Acad Sci 108:4531–4538

    Article  PubMed  Google Scholar 

  156. Vanhoecke BW, De Ryck TR, De Boel K, Wiles S, Boterberg T, Van de Wiele T, Swift S (2016) Low-dose irradiation affects the functional behavior of oral microbiota in the context of mucositis. Exp Biol Med 241:60–70

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Vijay-Kumar M et al (2010) Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science 328:228–231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Wallace BD et al (2010) Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science 330:831–835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  161. Wang Y, Kasper LH (2014) The role of microbiome in central nervous system disorders. Brain Behav Immun 38:1–12

    Article  CAS  PubMed  Google Scholar 

  162. Wang T et al (2012a) Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J 6:320

    Article  CAS  PubMed  Google Scholar 

  163. Wang X, Yang Y, Moore DR, Nimmo SL, Lightfoot SA, Huycke MM (2012b) 4-Hydroxy-2-nonenal mediates genotoxicity and bystander effects caused by Enterococcus faecalis-infected macrophages. Gastroenterology 142:543–551.e547

    Article  CAS  PubMed  Google Scholar 

  164. Wardill HR, Van Sebille YZ, Ciorba MA, Bowen JM (2018) Prophylactic probiotics for cancer therapy-induced diarrhoea: a meta-analysis. Curr Opin Support Palliat Care 12:187–197

    PubMed  Google Scholar 

  165. Windey K, De Preter V, Verbeke K (2012) Relevance of protein fermentation to gut health. Mol Nutr Food Res 56:184–196

    Article  CAS  Google Scholar 

  166. Winter SE et al (2013) Host-derived nitrate boosts growth of E. coli in the inflamed gut. Science 339:708–711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Yang Y (2015) Cancer immunotherapy: harnessing the immune system to battle cancer. J Clin Investig 125:3335–3337

    Article  PubMed  Google Scholar 

  169. Yoshimoto S et al (2013a) Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 499:97

    Article  CAS  PubMed  Google Scholar 

  170. Yoshimoto S et al (2013b) Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 499:97–101

    Article  CAS  PubMed  Google Scholar 

  171. Yu LX et al (2010) Endotoxin accumulation prevents carcinogen-induced apoptosis and promotes liver tumorigenesis in rodents. Hepatology 52:1322–1333

    Article  CAS  PubMed  Google Scholar 

  172. Zhan Y et al (2013) Gut microbiota protects against gastrointestinal tumorigenesis caused by epithelial injury. Cancer Res 73:7199–7210

    Article  CAS  PubMed  Google Scholar 

  173. Zhang H-L et al (2012) Profound impact of gut homeostasis on chemically-induced pro-tumorigenic inflammation and hepatocarcinogenesis in rats. J Hepatol 57:803–812

    Article  PubMed  Google Scholar 

  174. Zitvogel L, Galluzzi L, Viaud S, Vétizou M, Daillère R, Merad M, Kroemer G (2015) Cancer and the gut microbiota: an unexpected link. Sci Transl Med 7:271ps271

    Article  CAS  Google Scholar 

Download references

Funding

Not applicable.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Muhammad Arshad.

Ethics declarations

Conflict of interest

We declare that we have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Raza, M.H., Gul, K., Arshad, A. et al. Microbiota in cancer development and treatment. J Cancer Res Clin Oncol 145, 49–63 (2019). https://doi.org/10.1007/s00432-018-2816-0

Download citation

Keywords

  • Microbiome
  • Gut microbiota
  • Carcinogenesis
  • Cancer therapy