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The role of gut microbiota in the pathogenesis of colorectal cancer

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  • Published:
Tumor Biology

Abstract

The human gastrointestinal tract harbors a complex and abundant microbial community that can reach levels as high as 1013–1014 microorganisms in the colon. These microorganisms are essential to a host’s well-being in terms of nutrition and mucosa immunity. However, numerous studies have also implicated members of the colonic microbiota in the development of colorectal cancer (CRC). While CRC involves a genetic component where damaged DNA and genetic instability initiates a malignant transformation, environmental factors can also contribute to the onset of CRC. Furthermore, considering the constant exposure of the colonic mucosa to the microbiome and/or its metabolites, the mucosa has long been proposed to contribute to colon tumorigenesis. However, the mechanistic details of these associations remain unknown. Fortunately, due to technical and conceptual advances, progress in characterizing the taxonomic composition, metabolic capacity, and immunomodulatory activity of human gut microbiota have been made, thereby elucidating its role in human health and disease. Furthermore, the use of experimental animal models and clinical/epidemiological studies of environmental etiological factors has identified a correlation between gut microbiota composition and gastrointestinal cancers. Bacteria continuously stimulate activated immunity in the gut mucosa and also contribute to the metabolism of bile and food components. However, the highest levels of carcinogen production are also associated with gut anaerobic bacteria and can be lowered with live lactobacilli supplements. In this review, evidence regarding the relationship between microbiota and the development of CRC will be discussed, as well as the role for microbial manipulation in affecting disease development.

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Abbreviations

CRC:

Colorectal cancer

PCA:

Principle component analysis

IBD:

Inflammatory bowel diseases

TGF-β:

Transforming growth factor-β

ETBF:

Enterotoxigenic Bacteroides fragilis

CECs:

Colonic epithelial cells

BFT:

B. fragilis toxin

PRRs:

Pattern recognition receptors

PAMPs:

Pathogen-associated molecular patterns

TLRs:

Toll-like receptors

NLRs:

Nod-like receptors

NF-κB:

Nuclear factor κB

DMH:

Dimethylhydrazine

SIGIRR:

Single immunoglobulin IL-1 receptor-related molecule

STAT3:

Signal transducer and activator of transcription

MAM:

Metabolite methylazoxymethanol

DCA:

Deoxycholic acid

LCA:

Lithocholic acid

FBA:

Fecal bile acid

PGE2:

Prostaglandin E2

NOC:

Nitroso compounds

IFN-γ:

Interferon-γ

TNF-α:

Tumor necrosis factor-α

CFU:

Colony-forming units

GI:

Gastrointestinal

ROI:

Reactive oxygen intermediate

H2S:

Hydrogen sulfide

References

  1. Kostic AD, Gevers D, Pedamallu CS, Michaud M, Duke F, Earl AM, et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 2012;22(2):292–8.

    Article  PubMed  CAS  Google Scholar 

  2. Zur Hausen H. The search for infectious causes of human cancers: where and why. Virology. 2009;392(1):1–10.

    Article  PubMed  CAS  Google Scholar 

  3. Warren JR. Helicobacter: the ease and difficulty of a new discovery. Chem Med Chem. 2006;1(7):672–85.

    PubMed  CAS  Google Scholar 

  4. Rowland IR. The role of the gastrointestinal microbiota in colorectal cancer. Curr Pharm Des. 2009;15(13):1524–7.

    Article  PubMed  CAS  Google Scholar 

  5. Proctor LM. The Human Microbiome Project in 2011 and beyond. Cell Host Microbe. 2011;10(4):287–91.

    Article  PubMed  CAS  Google Scholar 

  6. Greer JB, O'Keefe SJ. Microbial induction of immunity, inflammation, and cancer. Front Physiol. 2011;1:168.

    Article  PubMed  Google Scholar 

  7. Zhu Y, Michelle Luo T, Jobin C, Young HA. Gut microbiota and probiotics in colon tumorigenesis. Cancer Lett. 2011;309(2):119–27.

    Article  PubMed  CAS  Google Scholar 

  8. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59–65.

    Article  PubMed  CAS  Google Scholar 

  9. Savage DC. Microbial ecology of the gastrointestinal tract. Annu Rev Microbiol. 1977;31:107–33.

    Article  PubMed  CAS  Google Scholar 

  10. Suau A, Bonnet R, Sutren M, Godon JJ, Gibson GR, Collins MD, et al. Direct analysis of genes encoding 16S rRNA from complex communities reveals many novel molecular species within the human gut. Appl Environ Microbiol. 1999;65(11):4799–807.

    PubMed  CAS  Google Scholar 

  11. Neish AS. Microbes in gastrointestinal health and disease. Gastroenterology. 2009;136(1):65–80.

    Article  PubMed  Google Scholar 

  12. Hakansson A, Molin G. Gut microbiota and inflammation. Nutrients. 2011;3(6):637–82.

    Article  PubMed  Google Scholar 

  13. Dethlefsen L, Eckburg PB, Bik EM, Relman DA. Assembly of the human intestinal microbiota. Trends Ecol Evol. 2006;21(9):517–23.

    Article  PubMed  Google Scholar 

  14. Claesson MJ, Cusack S, O'Sullivan O, Greene-Diniz R, de Weerd H, Flannery E, et al. Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci USA. 2011;108 Suppl 1:4586–91.

    Article  PubMed  CAS  Google Scholar 

  15. Marchesi JR. Human distal gut microbiome. Environ Microbiol. 2011;13(12):3088–102.

    Article  PubMed  Google Scholar 

  16. Goncharova GI, Dorofeĭchuk VG, Smolianskaia AZ, Sokolova KIA. Microbial ecology of the intestines in health and in pathology. Antibiot Khimioter. 1989;34(6):462–6.

    PubMed  CAS  Google Scholar 

  17. Stanghellini V, Barbara G, Cremon C, Cogliandro R, Antonucci A, Gabusi V, et al. Gut microbiota and related diseases: clinical features. Intern Emerg Med. 2010;5 Suppl 1:S57–63.

    Article  PubMed  Google Scholar 

  18. Tlaskalová-Hogenová H, Stepánková R, Hudcovic T, Tucková L, Cukrowska B, Lodinová-Zádníková R, et al. Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases. Immunol Lett. 2004;93(2–3):97–108.

    Article  PubMed  CAS  Google Scholar 

  19. Rastall RA. Bacteria in the gut: friends and foes and how to alter the balance. J Nutr. 2004;134(8 Suppl):2022S–6S.

    PubMed  CAS  Google Scholar 

  20. Mai V. Dietary modification of the intestinal microbiota. Nutr Rev. 2004;62(6 Pt 1):235–42.

    Article  PubMed  Google Scholar 

  21. Peek Jr RM, Blaser MJ. Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat Rev Cancer. 2002;2(1):28–37.

    Article  PubMed  CAS  Google Scholar 

  22. Gold JS, Bayar S, Salem RR. Association of Streptococcus bovis bacteremia with colonic neoplasia and extracolonic malignancy. Arch Surg. 2004;139(7):760–5.

    Article  PubMed  Google Scholar 

  23. Moore WE, Moore LH. Intestinal floras of populations that have a high risk of colon cancer. Appl Environ Microbiol. 1995;61(9):3202–7.

    PubMed  CAS  Google Scholar 

  24. Nakamura J, Kubota Y, Miyaoka M, Saitoh T, Mizuno F, Benno Y. Comparison of four microbial enzymes in Clostridia and Bacteroides isolated from human feces. Microbiol Immunol. 2002;46(7):487–90.

    PubMed  CAS  Google Scholar 

  25. McIntosh GH, Royle PJ, Playne MJ. A probiotic strain of L. acidophilus reduces DMH-induced large intestinal tumors in male Sprague-Dawley rats. Nutr Cancer. 1999;35(2):153–9.

    Article  PubMed  CAS  Google Scholar 

  26. Rowland IR, Bearne CA, Fischer R, Pool-Zobel BL. The effect of lactulose on DNA damage induced by DMH in the colon of human flora-associated rats. Nutr Cancer. 1996;26(1):37–47.

    Article  PubMed  CAS  Google Scholar 

  27. Swidsinski A, Khilkin M, Kerjaschki D, Schreiber S, Ortner M, Weber J, et al. Association between intraepithelial Escherichia coli and colorectal cancer. Gastroenterology. 1998;115(2):281–6.

    Article  PubMed  CAS  Google Scholar 

  28. de Martel C, Franceschi S. Infections and cancer: established associations and new hypotheses. Crit Rev Oncol Hematol. 2009;70(3):183–94.

    Article  PubMed  Google Scholar 

  29. Cuevas-Ramos G, Petit CR, Marcq I, Boury M, Oswald E, Nougayrède JP. Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells. Proc Natl Acad Sci USA. 2010;107(25):11537–42.

    Article  PubMed  CAS  Google Scholar 

  30. Ellmerich S, Djouder N, Schöller M, Klein JP. Production of cytokines by monocytes, epithelial and endothelial cells activated by Streptococcus bovis. Cytokine. 2000;12(1):26–31.

    Article  PubMed  CAS  Google Scholar 

  31. Marchesi JR, Dutilh BE, Hall N, Peters WH, Roelofs R, Boleij A, et al. Towards the human colorectal cancer microbiome. PLoS One. 2011;6(5):e20447.

    Article  PubMed  CAS  Google Scholar 

  32. Castellarin M, Warren RL, Freeman JD, Dreolini L, Krzywinski M, Strauss J, et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 2012;22(2):299–306.

    Article  PubMed  CAS  Google Scholar 

  33. Chen W, Liu F, Ling Z, Tong X, Xiang C. Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer. PLoS One. 2012;7(6):e39743.

    Article  PubMed  CAS  Google Scholar 

  34. Tjalsma H, Boleij A, Marchesi JR, Dutilh BE. A bacterial driver–passenger model for colorectal cancer: beyond the usual suspects. Nat Rev Microbiol. 2012;10(8):575–82.

    Article  PubMed  CAS  Google Scholar 

  35. Gueimonde M, Ouwehand A, Huhtinen H, Salminen E, Salminen S. Qualitative and quantitative analyses of the bifidobacterial microbiota in the colonic mucosa of patients with colorectal cancer, diverticulitis and inflammatory bowel disease. World J Gastroenterol. 2007;13(29):3985–9.

    PubMed  Google Scholar 

  36. Shen XJ, Rawls JF, Randall T, Burcal L, Mpande CN, Jenkins N, et al. Molecular characterization of mucosal adherent bacteria and associations with colorectal adenomas. Gut Microbes. 2010;1(3):138–47.

    Article  PubMed  Google Scholar 

  37. Sobhani I, Tap J, Roudot-Thoraval F, Roperch JP, Letulle S, Langella P, et al. Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS One. 2011;6(1):e16393.

    Article  PubMed  CAS  Google Scholar 

  38. Cummings JH, Macfarlane GT. The control and consequences of bacterial fermentation in the human colon. J Appl Bacteriol. 1991;70(6):443–59.

    Article  PubMed  CAS  Google Scholar 

  39. Hope ME, Hold GL, Kain R, El-Omar EM. Sporadic colorectal cancer—role of the commensal microbiota. FEMS Microbiol Lett. 2005;244(1):1–7.

    Article  PubMed  CAS  Google Scholar 

  40. Reddy BS, Mastromarino A, Wynder EL. Further leads on metabolic epidemiology of large bowel cancer. Cancer Res. 1975;35(11 Pt. 2):3403–6.

    PubMed  CAS  Google Scholar 

  41. Marteau PR, de Vrese M, Cellier CJ, Schrezenmeir J. Protection from gastrointestinal diseases with the use of probiotics. Am J Clin Nutr. 2001;73(2 Suppl):430S–6S.

    PubMed  CAS  Google Scholar 

  42. Balish E, Warner T. Enterococcus faecalis induces inflammatory bowel disease in interleukin-10 knockout mice. Am J Pathol. 2002;160(6):2253–7.

    Article  PubMed  CAS  Google Scholar 

  43. Kado S, Uchida K, Funabashi H, Iwata S, Nagata Y, Ando M, et al. Intestinal microflora are necessary for development of spontaneous adenocarcinoma of the large intestine in T-cell receptor beta chain and p53 double-knockout mice. Cancer Res. 2001;61(6):2395–8.

    PubMed  CAS  Google Scholar 

  44. Takaku K, Oshima M, Miyoshi H, Matsui M, Seldin MF, Taketo MM. Intestinal tumorigenesis in compound mutant mice of both Dpc4 (Smad4) and Apc genes. Cell. 1998;92(5):645–56.

    Article  PubMed  CAS  Google Scholar 

  45. Engle SJ, Ormsby I, Pawlowski S, Boivin GP, Croft J, Balish E, et al. Elimination of colon cancer in germ-free transforming growth factor beta 1-deficient mice. Cancer Res. 2002;62(22):6362–6.

    PubMed  CAS  Google Scholar 

  46. Erdman SE, Poutahidis T, Tomczak M, Rogers AB, Cormier K, Plank B, et al. CD4+ CD25+ regulatory T lymphocytes inhibit microbially induced colon cancer in Rag2-deficient mice. Am J Pathol. 2003;162(2):691–702.

    Article  PubMed  CAS  Google Scholar 

  47. Owen RW. Faecal steroids and colorectal carcinogenesis. Scand J Gastroenterol Suppl. 1997;222:76–82.

    PubMed  CAS  Google Scholar 

  48. Rubin DC, Shaker A, Levin MS. Chronic intestinal inflammation: inflammatory bowel disease and colitis-associated colon cancer. Front Immunol. 2012;3:107.

    Article  PubMed  Google Scholar 

  49. Moossavi S, Bishehsari F. Inflammation in sporadic colorectal cancer. Arch Iran Med. 2012;15(3):166–70.

    PubMed  CAS  Google Scholar 

  50. Virchow R. Cellular pathology. As based upon physiological and pathological histology. Lecture XVI—atheromatous affection of arteries. 1858. Nutr Rev. 1989;47(1):23–5.

    Article  PubMed  CAS  Google Scholar 

  51. Compare D, Nardone G. Contribution of gut microbiota to colonic and extracolonic cancer development. Dig Dis. 2011;29(6):554–61.

    Article  PubMed  Google Scholar 

  52. Terzić J, Grivennikov S, Karin E, Karin M. Inflammation and colon cancer. Gastroenterology. 2010;138(6):2101.e5–14.e5.

    Article  CAS  Google Scholar 

  53. Uronis JM, Mühlbauer M, Herfarth HH, Rubinas TC, Jones GS, Jobin C. Modulation of the intestinal microbiota alters colitis-associated colorectal cancer susceptibility. PLoS One. 2009;4(6):e6026.

    Article  PubMed  CAS  Google Scholar 

  54. Fasano A. Cellular microbiology: can we learn cell physiology from microorganisms? Am J Physiol. 1999;276(4 Pt 1):C765–76.

    PubMed  CAS  Google Scholar 

  55. Rhee KJ, Wu S, Wu X, Huso DL, Karim B, Franco AA, et al. Induction of persistent colitis by a human commensal, enterotoxigenic Bacteroides fragilis, in wild-type C57BL/6 mice. Infect Immun. 2009;77(4):1708–18.

    Article  PubMed  CAS  Google Scholar 

  56. Wu S, Morin PJ, Maouyo D, Sears CL. Bacteroides fragilis enterotoxin induces c-Myc expression and cellular proliferation. Gastroenterology. 2003;124(2):392–400.

    Article  PubMed  CAS  Google Scholar 

  57. Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X, Yen HR, et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med. 2009;15(9):1016–22.

    Article  PubMed  CAS  Google Scholar 

  58. DuPont AW, DuPont HL. The intestinal microbiota and chronic disorders of the gut. Nat Rev Gastroenterol Hepatol. 2011;8(9):523–31.

    Article  PubMed  Google Scholar 

  59. Chen GY, Shaw MH, Redondo G, Núñez G. The innate immune receptor Nod1 protects the intestine from inflammation-induced tumorigenesis. Cancer Res. 2008;68(24):10060–7.

    Article  PubMed  CAS  Google Scholar 

  60. Zhang G, Ghosh S. Toll-like receptor-mediated NF-kappaB activation: a phylogenetically conserved paradigm in innate immunity. J Clin Invest. 2001;107(1):13–9.

    Article  PubMed  CAS  Google Scholar 

  61. Wald D, Qin J, Zhao Z, Qian Y, Naramura M, Tian L, et al. SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling. Nat Immunol. 2003;4(9):920–7.

    Article  PubMed  CAS  Google Scholar 

  62. Xiao H, Gulen MF, Qin J, Yao J, Bulek K, Kish D, et al. The Toll-interleukin-1 receptor member SIGIRR regulates colonic epithelial homeostasis, inflammation, and tumorigenesis. Immunity. 2007;26(4):461–75.

    Article  PubMed  CAS  Google Scholar 

  63. Kadota C, Ishihara S, Aziz MM, Rumi MA, Oshima N, Mishima Y, et al. Down-regulation of single immunoglobulin interleukin-1R-related molecule (SIGIRR)/TIR8 expression in intestinal epithelial cells during inflammation. Clin Exp Immunol. 2010;162(2):348–61.

    Article  PubMed  CAS  Google Scholar 

  64. Gong J, Wei T, Stark RW, Jamitzky F, Heckl WM, Anders HJ, et al. Inhibition of Toll-like receptors TLR4 and 7 signaling pathways by SIGIRR: a computational approach. J Struct Biol. 2010;169(3):323–30.

    Article  PubMed  CAS  Google Scholar 

  65. Salcedo R, Worschech A, Cardone M, Jones Y, Gyulai Z, Dai RM, et al. MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18. J Exp Med. 2010;207(8):1625–36.

    Article  PubMed  CAS  Google Scholar 

  66. Fukata M, Chen A, Vamadevan AS, Cohen J, Breglio K, Krishnareddy S, et al. Toll-like receptor-4 promotes the development of colitis-associated colorectal tumors. Gastroenterology. 2007;133(6):1869–81.

    Article  PubMed  CAS  Google Scholar 

  67. Sears CL, Pardoll DM. Perspective: alpha-bugs, their microbial partners, and the link to colon cancer. J Infect Dis. 2011;203(3):306–11.

    Article  PubMed  Google Scholar 

  68. Boleij A, Tjalsma H. Gut bacteria in health and disease: a survey on the interface between intestinal microbiology and colorectal cancer. Biol Rev Camb Philos Soc. 2012;87(3):701–30.

    Article  PubMed  Google Scholar 

  69. Huycke MM, Abrams V, Moore DR. Enterococcus faecalis produces extracellular superoxide and hydrogen peroxide that damages colonic epithelial cell DNA. Carcinogenesis. 2002;23(3):529–36.

    Article  PubMed  CAS  Google Scholar 

  70. Wang X, Huycke MM. Extracellular superoxide production by Enterococcus faecalis promotes chromosomal instability in mammalian cells. Gastroenterology. 2007;132(2):551–61.

    Article  PubMed  CAS  Google Scholar 

  71. Wang X, Allen TD, May RJ, Lightfoot S, Houchen CW, Huycke MM. Enterococcus faecalis induces aneuploidy and tetraploidy in colonic epithelial cells through a bystander effect. Cancer Res. 2008;68(23):9909–17.

    Article  PubMed  CAS  Google Scholar 

  72. Nougayrède JP, Homburg S, Taieb F, Boury M, Brzuszkiewicz E, Gottschalk G, et al. Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science. 2006;313(5788):848–51.

    Article  PubMed  CAS  Google Scholar 

  73. Wu S, Shin J, Zhang G, Cohen M, Franco A, Sears CL. The Bacteroides fragilis toxin binds to a specific intestinal epithelial cell receptor. Infect Immun. 2006;74(9):5382–90.

    Article  PubMed  CAS  Google Scholar 

  74. Toprak NU, Yagci A, Gulluoglu BM, Akin ML, Demirkalem P, Celenk T, et al. A possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer. Clin Microbiol Infect. 2006;12(8):782–6.

    PubMed  CAS  Google Scholar 

  75. Goodwin AC, Destefano Shields CE, Wu S, Huso DL, Wu X, Murray-Stewart TR, et al. Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis. Proc Natl Acad Sci USA. 2011;108(37):15354–9.

    Article  PubMed  CAS  Google Scholar 

  76. Wu S, Rhee KJ, Zhang M, Franco A, Sears CL. Bacteroides fragilis toxin stimulates intestinal epithelial cell shedding and gamma-secretase-dependent E-cadherin cleavage. J Cell Sci. 2007;120(Pt 11):1944–52.

    Article  PubMed  CAS  Google Scholar 

  77. McCart AE, Vickaryous NK, Silver A. Apc mice: models, modifiers and mutants. Pathol Res Pract. 2008;204(7):479–90.

    Article  PubMed  Google Scholar 

  78. Näthke IS. The adenomatous polyposis coli protein: the Achilles heel of the gut epithelium. Annu Rev Cell Dev Biol. 2004;20:337–66.

    Article  PubMed  CAS  Google Scholar 

  79. Wang L, Yi T, Kortylewski M, Pardoll DM, Zeng D, Yu H. IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med. 2009;206(7):1457–64.

    Article  PubMed  CAS  Google Scholar 

  80. Housseau F, Sears CL. Enterotoxigenic Bacteroides fragilis (ETBF)-mediated colitis in Min (Apc+/−) mice: a human commensal-based murine model of colon carcinogenesis. Cell Cycle. 2010;9(1):3–5.

    Article  PubMed  CAS  Google Scholar 

  81. Mangan PR, Harrington LE, O'Quinn DB, Helms WS, Bullard DC, Elson CO, et al. Transforming growth factor-beta induces development of the T(H)17 lineage. Nature. 2006;441(7090):231–4.

    Article  PubMed  CAS  Google Scholar 

  82. DuPont HL. Clinical practice. Bacterial diarrhea. N Engl J Med. 2009;361(16):1560–9.

    Article  PubMed  CAS  Google Scholar 

  83. Karin M. Nuclear factor-kappaB in cancer development and progression. Nature. 2006;441(7092):431–6.

    Article  PubMed  CAS  Google Scholar 

  84. Yu H, Kortylewski M, Pardoll D. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol. 2007;7(1):41–51.

    Article  PubMed  CAS  Google Scholar 

  85. Cole CB, Fuller R, Mallet AK, Rowland IR. The influence of the host on expression of intestinal microbial enzyme activities involved in metabolism of foreign compounds. J Appl Bacteriol. 1985;59(6):549–53.

    Article  PubMed  CAS  Google Scholar 

  86. Steer TE, Johnson IT, Gee JM, Gibson GR. Metabolism of the soybean isoflavone glycoside genistin in vitro by human gut bacteria and the effect of prebiotics. Br J Nutr. 2003;90(3):635–42.

    Article  PubMed  CAS  Google Scholar 

  87. Takada H, Hirooka T, Hiramatsu Y, Yamamoto M. Effect of beta-glucuronidase inhibitor on azoxymethane-induced colonic carcinogenesis in rats. Cancer Res. 1982;42(1):331–34.

    PubMed  CAS  Google Scholar 

  88. Kim DH, Jin YH. Intestinal bacterial beta-glucuronidase activity of patients with colon cancer. Arch Pharm Res. 2001;24(6):564–7.

    Article  PubMed  CAS  Google Scholar 

  89. Rowland IR, Tanaka R. The effects of transgalactosylated oligosaccharides on gut flora metabolism in rats associated with a human faecal microflora. J Appl Bacteriol. 1993;74(6):667–74.

    Article  PubMed  CAS  Google Scholar 

  90. Davis CD, Milner JA. Gastrointestinal microflora, food components and colon cancer prevention. J Nutr Biochem. 2009;20(10):743–52.

    Article  PubMed  CAS  Google Scholar 

  91. Gill CI, Rowland IR. Diet and cancer: assessing the risk. Br J Nutr. 2002;88 Suppl 1:S73–87.

    Article  PubMed  CAS  Google Scholar 

  92. Reddy BS, Mangat S, Weisburger JH, Wynder EL. Effect of high-risk diets for colon carcinogenesis on intestinal mucosal and bacterial beta-glucuronidase activity in F344 rats. Cancer Res. 1977;37(10):3533–6.

    PubMed  CAS  Google Scholar 

  93. Mazière S, Meflah K, Tavan E, Champ M, Narbonne JF, Cassand P. Effect of resistant starch and/or fat-soluble vitamins A and E on the initiation stage of aberrant crypts in rat colon. Nutr Cancer. 1998;31(3):168–77.

    Article  PubMed  Google Scholar 

  94. Gråsten SM, Juntunen KS, Poutanen KS, Gylling HK, Miettinen TA, Mykkänen HM. Rye bread improves bowel function and decreases the concentrations of some compounds that are putative colon cancer risk markers in middle-aged women and men. J Nutr. 2000;130(9):2215–21.

    PubMed  Google Scholar 

  95. Lee JW, Shin JG, Kim EH, Kang HE, Yim IB, Kim JY, et al. Immunomodulatory and antitumor effects in vivo by the cytoplasmic fraction of Lactobacillus casei and Bifidobacterium longum. J Vet Sci. 2004;5(1):41–8.

    PubMed  Google Scholar 

  96. de Giorgio R, Blandizzi C. Targeting enteric neuroplasticity: diet and bugs as new key factors. Gastroenterology. 2010;138(5):1663–6.

    Article  PubMed  CAS  Google Scholar 

  97. Powolny A, Xu J, Loo G. Deoxycholate induces DNA damage and apoptosis in human colon epithelial cells expressing either mutant or wild-type p53. Int J Biochem Cell Biol. 2001;33(2):193–203.

    Article  PubMed  CAS  Google Scholar 

  98. Narahara H, Tatsuta M, Iishi H, Baba M, Uedo N, Sakai N, et al. K-ras point mutation is associated with enhancement by deoxycholic acid of colon carcinogenesis induced by azoxymethane, but not with its attenuation by all-trans-retinoic acid. Int J Cancer. 2000;88(2):157–61.

    Article  PubMed  CAS  Google Scholar 

  99. Radley S, Davis AE, Imray CH, Barker G, Morton DG, Baker PR, et al. Biliary bile acid profiles in familial adenomatous polyposis. Br J Surg. 1992;79(1):89–90.

    Article  PubMed  CAS  Google Scholar 

  100. Imray CH, Radley S, Davis A, Barker G, Hendrickse CW, Donovan IA, et al. Faecal unconjugated bile acids in patients with colorectal cancer or polyps. Gut. 1992;33(9):1239–45.

    Article  PubMed  CAS  Google Scholar 

  101. de Kok TM, van Maanen JM. Evaluation of fecal mutagenicity and colorectal cancer risk. Mutat Res. 2000;463(1):53–101.

    Article  PubMed  Google Scholar 

  102. Deschner EE, Cohen BI, Raicht RF. Acute and chronic effect of dietary cholic acid on colonic epithelial cell proliferation. Digestion. 1981;21(6):290–6.

    Article  PubMed  CAS  Google Scholar 

  103. Deschner EE, Raicht RF. Influence of bile on kinetic behavior of colonic epithelial cells of the rat. Digestion. 1979;19(5):322–7.

    Article  PubMed  CAS  Google Scholar 

  104. DeRubertis FR, Craven PA, Saito R. Bile salt stimulation of colonic epithelial proliferation. Evidence for involvement of lipoxygenase products. J Clin Invest. 1984;74(5):1614–24.

    Article  PubMed  CAS  Google Scholar 

  105. Hughes R, Kurth MJ, McGilligan V, McGlynn H, Rowland I. Effect of colonic bacterial metabolites on Caco-2 cell paracellular permeability in vitro. Nutr Cancer. 2008;60(2):259–66.

    Article  PubMed  CAS  Google Scholar 

  106. Heavey PM, Rowland IR. Microbial–gut interactions in health and disease. Gastrointestinal cancer. Best Pract Res Clin Gastroenterol. 2004;18(2):323–36.

    Article  PubMed  Google Scholar 

  107. Orrhage K, Sillerström E, Gustafsson JA, Nord CE, Rafter J. Binding of mutagenic heterocyclic amines by intestinal and lactic acid bacteria. Mutat Res. 1994;311(2):239–48.

    Article  PubMed  CAS  Google Scholar 

  108. Carman RJ, Van Tassell RL, Kingston DG, Bashir M, Wilkins TD. Conversion of IQ, a dietary pyrolysis carcinogen to a direct-acting mutagen by normal intestinal bacteria of humans. Mutat Res. 1988;206(3):335–42.

    Article  PubMed  CAS  Google Scholar 

  109. Owen RW, Spiegelhalder B, Bartsch H. Generation of reactive oxygen species by the faecal matrix. Gut. 2000;46(2):225–32.

    Article  PubMed  CAS  Google Scholar 

  110. Marnett LJ. Oxyradicals and DNA damage. Carcinogenesis. 2000;21(3):361–70.

    Article  PubMed  CAS  Google Scholar 

  111. Shacter E, Weitzman SA. Chronic inflammation and cancer. Oncology (Williston Park). 2002; 16(2):217–26, 229.

  112. Hughes R, Cross AJ, Pollock JR, Bingham S. Dose-dependent effect of dietary meat on endogenous colonic N-nitrosation. Carcinogenesis. 2001;22(1):199–202.

    Article  PubMed  CAS  Google Scholar 

  113. Massey RC, Key PE, Mallett AK, Rowland IR. An investigation of the endogenous formation of apparent total N-nitroso compounds in conventional microflora and germ-free rats. Food Chem Toxicol. 1988;26(7):595–600.

    Article  PubMed  CAS  Google Scholar 

  114. Rowland IR, Granli T, Bøckman OC, Key PE, Massey RC. Endogenous N-nitrosation in man assessed by measurement of apparent total N-nitroso compounds in faeces. Carcinogenesis. 1991;12(8):1395–401.

    Article  PubMed  CAS  Google Scholar 

  115. Pala V, Sieri S, Berrino F, Vineis P, Sacerdote C, Palli D, et al. Yogurt consumption and risk of colorectal cancer in the Italian European prospective investigation into cancer and nutrition cohort. Int J Cancer. 2011;129(11):2712–9.

    Article  PubMed  CAS  Google Scholar 

  116. de Vrese M, Schrezenmeir J. Probiotics, prebiotics, and synbiotics. Adv Biochem Eng Biotechnol. 2008;111:1–66.

    PubMed  Google Scholar 

  117. Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, et al. Enterotypes of the human gut microbiome. Nature. 2011;473(7346):174–80.

    Article  PubMed  CAS  Google Scholar 

  118. Corthésy B, Gaskins HR, Mercenier A. Cross-talk between probiotic bacteria and the host immune system. J Nutr. 2007;137(3 Suppl 2):781S–90S.

    PubMed  Google Scholar 

  119. Orlando A, Messa C, Linsalata M, Cavallini A, Russo F. Effects of Lactobacillus rhamnosus GG on proliferation and polyamine metabolism in HGC-27 human gastric and DLD-1 colonic cancer cell lines. Immunopharmacol Immunotoxicol. 2009;31(1):108–16.

    Article  PubMed  CAS  Google Scholar 

  120. Lee NK, Park JS, Park E, Paik HD. Adherence and anticarcinogenic effects of Bacillus polyfermenticus SCD in the large intestine. Lett Appl Microbiol. 2007;44(3):274–8.

    Article  PubMed  Google Scholar 

  121. Kim Y, Lee D, Kim D, Cho J, Yang J, Chung M, et al. Inhibition of proliferation in colon cancer cell lines and harmful enzyme activity of colon bacteria by Bifidobacterium adolescentis SPM0212. Arch Pharm Res. 2008;31(4):468–73.

    Article  PubMed  CAS  Google Scholar 

  122. Pool-Zobel BL, Neudecker C, Domizlaff I, Ji S, Schillinger U, Rumney C, et al. Lactobacillus- and Bifidobacterium-mediated antigenotoxicity in the colon of rats. Nutr Cancer. 1996;26(3):365–80.

    Article  PubMed  CAS  Google Scholar 

  123. Le Leu RK, Brown IL, Hu Y, Bird AR, Jackson M, Esterman A, et al. A synbiotic combination of resistant starch and Bifidobacterium lactis facilitates apoptotic deletion of carcinogen-damaged cells in rat colon. J Nutr. 2005;135(5):996–1001.

    PubMed  Google Scholar 

  124. Tlaskalová-Hogenová H, Stěpánková R, Kozáková H, Hudcovic T, Vannucci L, Tučková L, et al. The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases. Cell Mol Immunol. 2011;8(2):110–20.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Dr. Huanlong Qin for his critical reading of this manuscript.

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  1. Department of Surgery, The Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, 600 Yishan Road, Shanghai, 200233, People’s Republic of China

    Qingchao Zhu, Renyuan Gao, Wen Wu & Huanlong Qin

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  1. Qingchao Zhu
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  2. Renyuan Gao
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  3. Wen Wu
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Correspondence to Huanlong Qin.

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Zhu, Q., Gao, R., Wu, W. et al. The role of gut microbiota in the pathogenesis of colorectal cancer. Tumor Biol. 34, 1285–1300 (2013). https://doi.org/10.1007/s13277-013-0684-4

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