Open Access

The microbiome, its molecular mechanisms and its potential as a therapeutic strategy against colorectal carcinogenesis (Review)

  • Authors:
    • Stella Baliou
    • Maria Adamaki
    • Demetrios A. Spandidos
    • Anthony M. Kyriakopoulos
    • Ioannis Christodoulou
    • Vassilis Zoumpourlis
  • View Affiliations

  • Published online on: December 20, 2018     https://doi.org/10.3892/wasj.2018.6
  • Pages: 3-19
Metrics: HTML 0 views | PDF 0 views     Cited By (CrossRef): 0 citations

Abstract

Microbiota is receiving significant attention in the research field, given that it is essential in homeostasis and an indirect modulator of diseases, such as cancer. Humans harbor a multitude of microorganisms that affect both human health and disease. Colorectal cancer is a genetic disease that is composed of distinct subtypes. In all cases, the intestinal microbiota has recently emerged as a crucial factor that promotes tumor growth at all stages through various mechanisms, such as the modulation of inflammation, the stimulation of DNA damage and toxic metabolite synthesis. In this review, we assess the contribution of the gut microbiome to homeostasis, its role as a potentiator or blocker of tumor progression and the underlying molecular mechanisms; we harness human data from both meta‑omics analyses and studies using animal models. Furthermore, we evaluate the ways through which microbes can be manipulated for diagnostic and prognostic purposes, and how they respond to chemotherapy or immunotherapy. Mounting evidence suggests that the microbiota may be used for the development of novel therapeutic strategies against colon cancer.

References

1 

Iida N, Dzutsev A, Stewart CA, Smith L, Bouladoux N, Weingarten RA, Molina DA, Salcedo R, Back T, Cramer S, et al: Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science. 342:967–970. 2013.PubMed/NCBI View Article : Google Scholar

2 

Boleij A, Hechenbleikner EM, Goodwin AC, Badani R, Stein EM, Lazarev MG, Ellis B, Carroll KC, Albesiano E, Wick EC, et al: The Bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients. Clin Infect Dis. 60:208–215. 2015.PubMed/NCBI View Article : Google Scholar

3 

Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, et al: MetaHIT Consortium: A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 464:59–65. 2010.PubMed/NCBI View Article : Google Scholar

4 

Blaser MJ: Who are we? Indigenous microbes and the ecology of human diseases. EMBO Rep. 7:956–960. 2006.PubMed/NCBI View Article : Google Scholar

5 

Bultman SJ: Emerging roles of the microbiome in cancer. Carcinogenesis. 35:249–255. 2014.PubMed/NCBI View Article : Google Scholar

6 

Clemente JC, Ursell LK and Parfrey LW and Knight R: The impact of the gut microbiota on human health: An integrative view. Cell. 148:1258–1270. 2012.PubMed/NCBI View Article : Google Scholar

7 

Plottel CS and Blaser MJ: Microbiome and malignancy. Cell Host Microbe. 10:324–335. 2011.PubMed/NCBI View Article : Google Scholar

8 

Petersen C and Round JL: Defining dysbiosis and its influence on host immunity and disease. Cell Microbiol. 16:1024–1033. 2014.PubMed/NCBI View Article : Google Scholar

9 

Dietert RR and Dietert JM: The microbiome and sustainable healthcare. Healthcare (Basel). 3:100–129. 2015.PubMed/NCBI View Article : Google Scholar

10 

Arslan N: Obesity, fatty liver disease and intestinal microbiota. World J Gastroenterol. 20:16452–16463. 2014.PubMed/NCBI View Article : Google Scholar

11 

Schwabe RF and Jobin C: The microbiome and cancer. Nat Rev Cancer. 13:800–812. 2013.PubMed/NCBI View Article : Google Scholar

12 

Garrett WS: Cancer and the microbiota. Science. 348:80–86. 2015.PubMed/NCBI View Article : Google Scholar

13 

Human Microbiome Project Consortium: Structure, function and diversity of the healthy human microbiome. Nature. 486:207–214. 2012.PubMed/NCBI View Article : Google Scholar

14 

Grice EA and Segre JA: The skin microbiome. Nat Rev Microbiol. 9:244–253. 2011.PubMed/NCBI View Article : Google Scholar

15 

Suau A, Bonnet R, Sutren M, Godon JJ, Gibson GR, Collins MD and Doré J: Direct analysis of genes encoding 16S rRNA from complex communities reveals many novel molecular species within the human gut. Appl Environ Microbiol. 65:4799–4807. 1999.PubMed/NCBI

16 

Savage DC: Microbial ecology of the gastrointestinal tract. Annu Rev Microbiol. 31:107–133. 1977.PubMed/NCBI View Article : Google Scholar

17 

Neish AS: Microbes in gastrointestinal health and disease. Gastroenterology. 136:65–80. 2009.PubMed/NCBI View Article : Google Scholar

18 

Goncharova GI, Dorofeĭchuk VG, Smolianskaia AZ and Sokolova KIa: Microbial ecology of the intestines in health and in pathology. Antibiot Khimioter. 34:462–466. 1989.(In Russian). PubMed/NCBI

19 

Dominguez-Bello MG, Blaser MJ, Ley RE and Knight R: Development of the human gastrointestinal microbiota and insights from high-throughput sequencing. Gastroenterology. 140:1713–1719. 2011.PubMed/NCBI View Article : Google Scholar

20 

Mulder IE, Schmidt B, Lewis M, Delday M, Stokes CR, Bailey M, Aminov RI, Gill BP, Pluske JR, Mayer CD, et al: Restricting microbial exposure in early life negates the immune benefits associated with gut colonization in environments of high microbial diversity. PLoS One. 6(e28279)2011.PubMed/NCBI View Article : Google Scholar

21 

Claesson MJ, Cusack S, O'Sullivan O, Greene-Diniz R, de Weerd H, Flannery E, Marchesi JR, Falush D, Dinan T, Fitzgerald G, et al: Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci USA. 108((Suppl 1)): 4586–4591. 2011.PubMed/NCBI View Article : Google Scholar

22 

Rajilić-Stojanović M, Heilig HGHJ, Molenaar D, Kajander K, Surakka A, Smidt H and de Vos WM: Development and application of the human intestinal tract chip, a phylogenetic microarray: Analysis of universally conserved phylotypes in the abundant microbiota of young and elderly adults. Environ Microbiol. 11:1736–1751. 2009.PubMed/NCBI View Article : Google Scholar

23 

Turnbaugh PJ, Bäckhed F, Fulton L and Gordon JI: Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe. 3:213–223. 2008.PubMed/NCBI View Article : Google Scholar

24 

Zwielehner J, Liszt K, Handschur M, Lassl C, Lapin A and Haslberger AG: Combined PCR-DGGE fingerprinting and quantitative-PCR indicates shifts in fecal population sizes and diversity of Bacteroides, bifidobacteria and Clostridium cluster IV in institutionalized elderly. Exp Gerontol. 44:440–446. 2009.PubMed/NCBI View Article : Google Scholar

25 

Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE and Relman DA: Diversity of the human intestinal microbial flora. Science. 308:1635–1638. 2005.PubMed/NCBI View Article : Google Scholar

26 

Sommer F and Bäckhed F: The gut microbiota - masters of host development and physiology. Nat Rev Microbiol. 11:227–238. 2013.PubMed/NCBI View Article : Google Scholar

27 

Bäckhed F, Ley RE, Sonnenburg JL, Peterson DA and Gordon JI: Host-bacterial mutualism in the human intestine. Science. 307:1915–1920. 2005.PubMed/NCBI View Article : Google Scholar

28 

Tlaskalová-Hogenová H, Stepánková R, Hudcovic T, Tucková L, Cukrowska B, Lodinová-Zádníková R, Kozáková H, Rossmann P, Bártová J, Sokol D, et al: Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases. Immunol Lett. 93:97–108. 2004.PubMed/NCBI View Article : Google Scholar

29 

Wang L, Zhao N, Zhang F, Yue W and Liang M: Effect of taurine on leucocyte function. Eur J Pharmacol. 616:275–280. 2009.PubMed/NCBI View Article : Google Scholar

30 

O'Hara AM and Shanahan F: The gut flora as a forgotten organ. EMBO Rep. 7:688–693. 2006.PubMed/NCBI View Article : Google Scholar

31 

Proctor LM: The human microbiome project in 2011 and beyond. Cell Host Microbe. 10:287–291. 2011.PubMed/NCBI View Article : Google Scholar

32 

Weisburger JH, Reddy BS, Narisawa T and Wynder EL: Germ-free status and colon tumor induction by N-methyl-N'-nitro-N-nitrosoguanidine. Proc Soc Exp Biol Med. 148:1119–1121. 1975.PubMed/NCBI

33 

Peterson DA, Frank DN, Pace NR and Gordon JI: Metagenomic approaches for defining the pathogenesis of inflammatory bowel diseases. Cell Host Microbe. 3:417–427. 2008.PubMed/NCBI View Article : Google Scholar

34 

Walsh CJ, Guinane CM, O'Toole PW and Cotter PD: Beneficial modulation of the gut microbiota. FEBS Lett. 588:4120–4130. 2014.PubMed/NCBI View Article : Google Scholar

35 

Kamada N and Núñez G: Role of the gut microbiota in the development and function of lymphoid cells. J Immunol. 190:1389–1395. 2013.PubMed/NCBI View Article : Google Scholar

36 

Blaser MJ and Falkow S: What are the consequences of the disappearing human microbiota? Nat Rev Microbiol. 7:887–894. 2009.PubMed/NCBI View Article : Google Scholar

37 

Hooper LV and Macpherson AJ: Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat Rev Immunol. 10:159–169. 2010.PubMed/NCBI View Article : Google Scholar

38 

Palmer C, Bik EM, DiGiulio DB, Relman DA and Brown PO: Development of the human infant intestinal microbiota. PLoS Biol. 5(e177)2007.PubMed/NCBI View Article : Google Scholar

39 

Neish AS: Mucosal immunity the microbiome. Ann Am Thorac Soc. 11((Suppl 1)): S28–S32. 2014.PubMed/NCBI View Article : Google Scholar

40 

Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK and Knight R: Diversity, stability and resilience of the human gut microbiota. Nature. 489:220–230. 2012.PubMed/NCBI View Article : Google Scholar

41 

Morgan XC and Huttenhower C: Chapter 12: Human microbiome analysis. PLOS Comput Biol. 8(e1002808)2012.PubMed/NCBI View Article : Google Scholar

42 

Hooper LV, Littman DR and Macpherson AJ: Interactions between the microbiota and the immune system. Science. 336:1268–1273. 2012.PubMed/NCBI View Article : Google Scholar

43 

Khoruts A, Dicksved J, Jansson JK and Sadowsky MJ: Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea. J Clin Gastroenterol. 44:354–360. 2010.PubMed/NCBI View Article : Google Scholar

44 

Reid G, Younes JA, Van der Mei HC, Gloor GB, Knight R and Busscher HJ: Microbiota restoration: Natural and supplemented recovery of human microbial communities. Nat Rev Microbiol. 9:27–38. 2011.PubMed/NCBI View Article : Google Scholar

45 

Swiatczak B, Rescigno M and Cohen IR: Systemic features of immune recognition in the gut. Microbes Infect. 13:983–991. 2011.PubMed/NCBI View Article : Google Scholar

46 

Arthur JC and Jobin C: The struggle within Microbial influences on colorectal cancer. Inflamm Bowel Dis. 17:396–409. 2011.PubMed/NCBI View Article : Google Scholar

47 

Ley RE, Bäckhed F, Turnbaugh P, Lozupone CA, Knight RD and Gordon JI: Obesity alters gut microbial ecology. Proc Natl Acad Sci USA. 102:11070–11075. 2005.PubMed/NCBI View Article : Google Scholar

48 

Ivanov II, Frutos R de L, Manel N, Yoshinaga K, Rifkin DB, Sartor RB, Finlay BB and Littman DR: Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe. 4:337–349. 2008.PubMed/NCBI View Article : Google Scholar

49 

Johansson MEV, Jakobsson HE, Holmén-Larsson J, Schütte A, Ermund A, Rodríguez-Piñeiro AM, Arike L, Wising C, Svensson F, Bäckhed F, et al: Normalization of host intestinal mucus layers requires long-term microbial colonization. Cell Host Microbe. 18:582–592. 2015.PubMed/NCBI View Article : Google Scholar

50 

Spiljar M, Merkler D and Trajkovski M: The immune system bridges the gut microbiota with systemic energy homeostasis: focus on TLRs, mucosal barrier, and SCFAs. Front Immunol. 8(1353)2017.PubMed/NCBI View Article : Google Scholar

51 

Round JL and Mazmanian SK: Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci USA. 107:12204–12209. 2010.PubMed/NCBI View Article : Google Scholar

52 

Hepworth MR, Monticelli LA, Fung TC, Ziegler CG, Grunberg S, Sinha R, Mantegazza AR, Ma HL, Crawford A, Angelosanto JM, et al: Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria. Nature. 498:113–117. 2013.PubMed/NCBI View Article : Google Scholar

53 

Gaboriau-Routhiau V, Rakotobe S, Lécuyer E, Mulder I, Lan A, Bridonneau C, Rochet V, Pisi A, De Paepe M, Brandi G, et al: The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity. 31:677–689. 2009.PubMed/NCBI View Article : Google Scholar

54 

Garland CD, Lee A and Dickson MR: Segmented filamentous bacteria in the rodent small intestine: Their colonization of growing animals and possible role in host resistance to Salmonella. Microb Ecol. 8:181–190. 1982.PubMed/NCBI View Article : Google Scholar

55 

Yang Y, Torchinsky MB, Gobert M, Xiong H, Xu M, Linehan JL, Alonzo F, Ng C, Chen A, Lin X, et al: Focused specificity of intestinal TH17 cells towards commensal bacterial antigens. Nature. 510:152–156. 2014.PubMed/NCBI View Article : Google Scholar

56 

Schnupf P, Gaboriau-Routhiau V and Cerf-Bensussan N: Host interactions with segmented filamentous bacteria: An unusual trade-off that drives the post-natal maturation of the gut immune system. Semin Immunol. 25:342–351. 2013.PubMed/NCBI View Article : Google Scholar

57 

Wu HJ, Ivanov II, Darce J, Hattori K, Shima T, Umesaki Y, Littman DR, Benoist C and Mathis D: Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity. 32:815–827. 2010.PubMed/NCBI View Article : Google Scholar

58 

Song X, Gao H, Lin Y, Yao Y, Zhu S, Wang J, Liu Y, Yao X, Meng G, Shen N, et al: Alterations in the microbiota drive interleukin-17C production from intestinal epithelial cells to promote tumorigenesis. Immunity. 40:140–152. 2014.PubMed/NCBI View Article : Google Scholar

59 

Xu M, Pokrovskii M, Ding Y, Yi R, Au C, Harrison OJ, Galan C, Belkaid Y, Bonneau R and Littman DR: c-MAF-dependent regulatory T cells mediate immunological tolerance to a gut pathobiont. Nature. 554:373–377. 2018.PubMed/NCBI View Article : Google Scholar

60 

Kamada N and Núñez G: Regulation of the immune system by the resident intestinal bacteria. Gastroenterology. 146:1477–1488. 2014.PubMed/NCBI View Article : Google Scholar

61 

Martín R, Miquel S, Chain F, Natividad JM, Jury J, Lu J, Sokol H, Theodorou V, Bercik P, Verdu EF, et al: Faecalibacterium prausnitzii prevents physiological damages in a chronic low-grade inflammation murine model. BMC Microbiol. 15(67)2015.PubMed/NCBI View Article : Google Scholar

62 

Honda K and Littman DR: The microbiota in adaptive immune homeostasis and disease. Nature. 535:75–84. 2016.PubMed/NCBI View Article : Google Scholar

63 

Naik S, Bouladoux N, Wilhelm C, Molloy MJ, Salcedo R, Kastenmuller W, Deming C, Quinones M, Koo L, Conlan S, et al: Compartmentalized control of skin immunity by resident commensals. Science. 337:1115–1119. 2012.PubMed/NCBI View Article : Google Scholar

64 

Naik S, Bouladoux N, Linehan JL, Han SJ, Harrison OJ, Wilhelm C, Conlan S, Himmelfarb S, Byrd AL, Deming C, et al: Commensal-dendritic-cell interaction specifies a unique protective skin immune signature. Nature. 520:104–108. 2015.PubMed/NCBI View Article : Google Scholar

65 

Hajishengallis G, Liang S, Payne MA, Hashim A, Jotwani R, Eskan MA, McIntosh ML, Alsam A, Kirkwood KL, Lambris JD, et al: Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe. 10:497–506. 2011.PubMed/NCBI View Article : Google Scholar

66 

Hajishengallis G and Lamont RJ: Breaking bad: Manipulation of the host response by Porphyromonas gingivalis. Eur J Immunol. 44:328–338. 2014.PubMed/NCBI View Article : Google Scholar

67 

Abt MC, Osborne LC, Monticelli LA, Doering TA, Alenghat T, Sonnenberg GF, Paley MA, Antenus M, Williams KL, Erikson J, et al: Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity. 37:158–170. 2012.PubMed/NCBI View Article : Google Scholar

68 

Belkaid Y and Naik S: Compartmentalized and systemic control of tissue immunity by commensals. Nat Immunol. 14:646–653. 2013.PubMed/NCBI View Article : Google Scholar

69 

Ichinohe T, Pang IK, Kumamoto Y, Peaper DR, Ho JH, Murray TS and Iwasaki A: Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc Natl Acad Sci USA. 108:5354–5359. 2011.PubMed/NCBI View Article : Google Scholar

70 

Chervonsky AV: Microbiota autoimmunity. Cold Spring Harb Perspect Biol. 5(a007294)2013.PubMed/NCBI View Article : Google Scholar

71 

Lee YK, Menezes JS, Umesaki Y and Mazmanian SK: Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA. 108((Suppl 1)): 4615–4622. 2011.PubMed/NCBI View Article : Google Scholar

72 

Kim YG, Udayanga KGS, Totsuka N, Weinberg JB, Núñez G and Shibuya A: Gut dysbiosis promotes M2 macrophage polarization and allergic airway inflammation via fungi-induced PGE2. Cell Host Microbe. 15:95–102. 2014.PubMed/NCBI View Article : Google Scholar

73 

Mangeney M, Pothlichet J, Renard M, Ducos B and Heidmann T: Endogenous retrovirus expression is required for murine melanoma tumor growth in vivo. Cancer Res. 65:2588–2591. 2005.PubMed/NCBI View Article : Google Scholar

74 

Vaishnava S, Behrendt CL, Ismail AS, Eckmann L and Hooper LV: Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface. Proc Natl Acad Sci USA. 105:20858–20863. 2008.PubMed/NCBI View Article : Google Scholar

75 

Ménard S, Cerf-Bensussan N and Heyman M: Multiple facets of intestinal permeability and epithelial handling of dietary antigens. Mucosal Immunol. 3:247–259. 2010.PubMed/NCBI View Article : Google Scholar

76 

Mortha A, Chudnovskiy A, Hashimoto D, Bogunovic M, Spencer SP, Belkaid Y and Merad M: Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis. Science. 343(1249288)2014.PubMed/NCBI View Article : Google Scholar

77 

Rescigno M: Intestinal microbiota and its effects on the immune system. Cell Microbiol. 16:1004–1013. 2014.PubMed/NCBI View Article : Google Scholar

78 

Siegel R, Desantis C and Jemal A: Colorectal cancer statistics 2014. CA Cancer J Clin. 64:104–117. 2014.PubMed/NCBI View Article : Google Scholar

79 

Shen H, Yang J, Huang Q, Jiang MJ, Tan YN, Fu JF, Zhu LZ, Fang XF and Yuan Y: Different treatment strategies and molecular features between right-sided and left-sided colon cancers. World J Gastroenterol. 21:6470–6478. 2015.PubMed/NCBI View Article : Google Scholar

80 

Tamas K, Walenkamp AM, de Vries EG, van Vugt MA, Beets-Tan RG, van Etten B, de Groot DJ and Hospers GA: Rectal and colon cancer: Not just a different anatomic site. Cancer Treat Rev. 41:671–679. 2015.PubMed/NCBI View Article : Google Scholar

81 

Carethers JM and Jung BH: Genetics and genetic biomarkers in sporadic colorectal Cancer. Gastroenterology. 149:1177–1190.e3. 2015.PubMed/NCBI View Article : Google Scholar

82 

Watson AJ and Collins PD: Colon cancer A civilization disorder. Dig Dis. 29:222–228. 2011.PubMed/NCBI View Article : Google Scholar

83 

Starnes CO: Coley's toxins in perspective. Nature. 357:11–12. 1992.PubMed/NCBI View Article : Google Scholar

84 

Hoption Cann SA, van Netten JP and van Netten C: Dr William Coley and tumour regression: A place in history or in the future. Postgrad Med J. 79:672–680. 2003.PubMed/NCBI

85 

Grange JM, Bottasso O, Stanford CA and Stanford JL: The use of mycobacterial adjuvant-based agents for immunotherapy of cancer. Vaccine. 26:4984–4990. 2008.PubMed/NCBI View Article : Google Scholar

86 

Reddy BS, Mastromarino A and Wynder EL: Further leads on metabolic epidemiology of large bowel cancer. Cancer Res. 35:3403–3406. 1975.PubMed/NCBI

87 

Schreiber H, Nettesheim P, Lijinsky W, Richter CB and Walburg HE Jr: Induction of lung cancer in germfree, specific-pathogen-free, and infected rats by N-nitrosoheptamethyleneimine: Enhancement by respiratory infection. J Natl Cancer Inst. 49:1107–1114. 1972.PubMed/NCBI

88 

Dapito DH, Mencin A, Gwak GY, Pradere JP, Jang MK, Mederacke I, Caviglia JM, Khiabanian H, Adeyemi A, Bataller R, et al: Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4. Cancer Cell. 21:504–516. 2012.PubMed/NCBI View Article : Google Scholar

89 

Reddy BS and Watanabe K: Effect of intestinal microflora on 2,2'-dimethyl-4-aminobiphenyl-induced carcinogenesis in F344 rats. J Natl Cancer Inst. 61:1269–1271. 1978.PubMed/NCBI

90 

Uronis JM, Mühlbauer M, Herfarth HH, Rubinas TC, Jones GS and Jobin C: Modulation of the intestinal microbiota alters colitis-associated colorectal cancer susceptibility. PLoS One. 4(e6026)2009.PubMed/NCBI View Article : Google Scholar

91 

Lofgren JL, Whary MT, Ge Z, Muthupalani S, Taylor NS, Mobley M, Potter A, Varro A, Eibach D, Suerbaum S, et al: Lack of commensal flora in Helicobacter pylori-infected INS-GAS mice reduces gastritis and delays intraepithelial neoplasia. Gastroenterology. 140:210–220. 2011.PubMed/NCBI View Article : Google Scholar

92 

Vannucci L, Stepankova R, Kozakova H, Fiserova A, Rossmann P and Tlaskalova-Hogenova H: Colorectal carcinogenesis in germ-free and conventionally reared rats: Different intestinal environments affect the systemic immunity. Int J Oncol. 32:609–617. 2008.PubMed/NCBI View Article : Google Scholar

93 

Dove WF, Clipson L, Gould KA, Luongo C, Marshall DJ, Moser AR, Newton MA and Jacoby RF: Intestinal neoplasia in the ApcMin mouse: Independence from the microbial and natural killer (beige locus) status. Cancer Res. 57:812–814. 1997.PubMed/NCBI

94 

Yoshimoto S, Loo TM, Atarashi K, Kanda H, Sato S, Oyadomari S, Iwakura Y, Oshima K, Morita H, Hattori M, et al: Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature. 499:97–101. 2013.PubMed/NCBI View Article : Google Scholar

95 

Chen GY, Shaw MH, Redondo G and Núñez G: The innate immune receptor Nod1 protects the intestine from inflammation-induced tumorigenesis. Cancer Res. 68:10060–10067. 2008.PubMed/NCBI View Article : Google Scholar

96 

Grivennikov SI, Wang K, Mucida D, Stewart CA, Schnabl B, Jauch D, Taniguchi K, Yu GY, Osterreicher CH, Hung KE, et al: Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature. 491:254–258. 2012.PubMed/NCBI View Article : Google Scholar

97 

Klimesova K, Kverka M, Zakostelska Z, Hudcovic T, Hrncir T, Stepankova R, Rossmann P, Ridl J, Kostovcik M, Mrazek J, et al: Altered gut microbiota promotes colitis-associated cancer in IL-1 receptor-associated kinase M-deficient mice. Inflamm Bowel Dis. 19:1266–1277. 2013.PubMed/NCBI View Article : Google Scholar

98 

Garrett WS, Punit S, Gallini CA, Michaud M, Zhang D, Sigrist KS, Lord GM, Glickman JN and Glimcher LH: Colitis-associated colorectal cancer driven by T-bet deficiency in dendritic cells. Cancer Cell. 16:208–219. 2009.PubMed/NCBI View Article : Google Scholar

99 

Kado S, Uchida K, Funabashi H, Iwata S, Nagata Y, Ando M, Onoue M, Matsuoka Y, Ohwaki M and Morotomi M: 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. 61:2395–2398. 2001.PubMed/NCBI

100 

Engle SJ, Ormsby I, Pawlowski S, Boivin GP, Croft J, Balish E and Doetschman T: Elimination of colon cancer in germ-free transforming growth factor beta 1-deficient mice. Cancer Res. 62:6362–6366. 2002.PubMed/NCBI

101 

Erdman SE, Poutahidis T, Tomczak M, Rogers AB, Cormier K, Plank B, Horwitz BH and Fox JG: CD4+ CD25+ regulatory T lymphocytes inhibit microbially induced colon cancer in Rag2-deficient mice. Am J Pathol. 162:691–702. 2003.PubMed/NCBI View Article : Google Scholar

102 

Garrett WS, Lord GM, Punit S, Lugo-Villarino G, Mazmanian SK, Ito S, Glickman JN and Glimcher LH: Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell. 131:33–45. 2007.PubMed/NCBI View Article : Google Scholar

103 

Garrett WS, Gallini CA, Yatsunenko T, Michaud M, DuBois A, Delaney ML, Punit S, Karlsson M, Bry L, Glickman JN, et al: Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. Cell Host Microbe. 8:292–300. 2010.PubMed/NCBI View Article : Google Scholar

104 

Balish E and Warner T: Enterococcus faecalis induces inflammatory bowel disease in interleukin-10 knockout mice. Am J Pathol. 160:2253–2257. 2002.PubMed/NCBI View Article : Google Scholar

105 

Zhan Y, Chen PJ, Sadler WD, Wang F, Poe S, Núñez G, Eaton KA and Chen GY: Gut microbiota protects against gastrointestinal tumorigenesis caused by epithelial injury. Cancer Res. 73:7199–7210. 2013.PubMed/NCBI View Article : Google Scholar

106 

Hussain SP, Hofseth LJ and Harris CC: Radical causes of cancer. Nat Rev Cancer. 3:276–285. 2003.PubMed/NCBI View Article : Google Scholar

107 

Maddocks ODK, Short AJ, Donnenberg MS, Bader S and Harrison DJ: Attaching and effacing Escherichia coli downregulate DNA mismatch repair protein in vitro and are associated with colorectal adenocarcinomas in humans. PLoS One. 4(e5517)2009.PubMed/NCBI View Article : Google Scholar

108 

Salcedo R, Worschech A, Cardone M, Jones Y, Gyulai Z, Dai RM, Wang E, Ma W, Haines D, O'hUigin C, et al: MyD88-mediated signaling prevents development of adenocarcinomas of the colon: Role of interleukin 18. J Exp Med. 207:1625–1636. 2010.PubMed/NCBI View Article : Google Scholar

109 

Saleh M and Trinchieri G: Innate immune mechanisms of colitis and colitis-associated colorectal cancer. Nat Rev Immunol. 11:9–20. 2011.PubMed/NCBI View Article : Google Scholar

110 

Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S and Medzhitov R: Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell. 118:229–241. 2004.PubMed/NCBI View Article : Google Scholar

111 

Sears CL and Garrett WS: Microbes, microbiota, and colon cancer. Cell Host Microbe. 15:317–328. 2014.PubMed/NCBI View Article : Google Scholar

112 

Eslick GD: Helicobacter pylori infection causes gastric cancer? A review of the epidemiological, meta-analytic, and experimental evidence. World J Gastroenterol. 12:2991–2999. 2006.PubMed/NCBI View Article : Google Scholar

113 

Buti L, Spooner E, van der Veen AG, Rappuoli R, Covacci A and Ploegh HL: Helicobacter pylori cytotoxin-associated gene A (CagA) subverts the apoptosis-stimulating protein of p53 (ASPP2) tumor suppressor pathway of the host. Proc Natl Acad Sci USA. 108:9238–9243. 2011.PubMed/NCBI View Article : Google Scholar

114 

Wroblewski LE, Peek RM Jr and Wilson KT: Helicobacter pylori and gastric cancer: Factors that modulate disease risk. Clin Microbiol Rev. 23:713–739. 2010.PubMed/NCBI View Article : Google Scholar

115 

Marshall BJ and Warren JR: Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1:1311–1315. 1984.PubMed/NCBI View Article : Google Scholar

116 

Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X, Yen HR, Huso DL, Brancati FL, Wick E, McAllister F, et al: A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med. 15:1016–1022. 2009.PubMed/NCBI View Article : Google Scholar

117 

Geis AL, Fan H, Wu X, Wu S, Huso DL, Wolfe JL, Sears CL, Pardoll DM and Housseau F: Regulatory T-cell response to enterotoxigenic Bacteroides fragilis colonization triggers IL17-dependent colon carcinogenesis. Cancer Discov. 5:1098–1109. 2015.PubMed/NCBI View Article : Google Scholar

118 

Kim SC, Tonkonogy SL, Albright CA, Tsang J, Balish EJ, Braun J, Huycke MM and Sartor RB: Variable phenotypes of enterocolitis in interleukin 10-deficient mice monoassociated with two different commensal bacteria. Gastroenterology. 128:891–906. 2005.PubMed/NCBI View Article : Google Scholar

119 

Wang X, Yang Y, Moore DR, Nimmo SL, Lightfoot SA and Huycke MM: 4-Hydroxy-2-nonenal mediates genotoxicity and bystander effects caused by Enterococcus faecalis-infected macrophages. Gastroenterology. 142:543–551, e7. 2012.PubMed/NCBI View Article : Google Scholar

120 

Kostic AD, Chun E, Robertson L, Glickman JN, Gallini CA, Michaud M, Clancy TE, Chung DC, Lochhead P, Hold GL, et al: Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe. 14:207–215. 2013.PubMed/NCBI View Article : Google Scholar

121 

Abed J, Emgård JEM, Zamir G, Faroja M, Almogy G, Grenov A, Sol A, Naor R, Pikarsky E, Atlan KA, et al: Fap2 mediates fusobacterium nucleatum colorectal adenocarcinoma enrichment by binding to tumor-expressed Gal-GalNAc. Cell Host Microbe. 20:215–225. 2016.PubMed/NCBI View Article : Google Scholar

122 

Signat B, Roques C, Poulet P and Duffaut D: Fusobacterium nucleatum in periodontal health and disease. Curr Issues Mol Biol. 13:25–36. 2011.PubMed/NCBI

123 

Strauss J, Kaplan GG, Beck PL, Rioux K, Panaccione R, Devinney R, Lynch T and Allen-Vercoe E: Invasive potential of gut mucosa-derived Fusobacterium nucleatum positively correlates with IBD status of the host. Inflamm Bowel Dis. 17:1971–1978. 2011.PubMed/NCBI View Article : Google Scholar

124 

Sobhani I, Tap J, Roudot-Thoraval F, Roperch JP, Letulle S, Langella P, Corthier G, Tran Van Nhieu J and Furet JP: Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS One. 6(e16393)2011.PubMed/NCBI View Article : Google Scholar

125 

Castellarin M, Warren RL, Freeman JD, Dreolini L, Krzywinski M, Strauss J, Barnes R, Watson P, Allen-Vercoe E, Moore RA, et al: Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 22:299–306. 2012.PubMed/NCBI View Article : Google Scholar

126 

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

127 

Gur C, Ibrahim Y, Isaacson B, Yamin R, Abed J, Gamliel M, Enk J, Bar-On Y, Stanietsky-Kaynan N, Coppenhagen-Glazer S, 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.PubMed/NCBI View Article : Google Scholar

128 

Liu H, Redline RW and Han YW: Fusobacterium nucleatum induces fetal death in mice via stimulation of TLR4-mediated placental inflammatory response. J Immunol. 179:2501–2508. 2007.PubMed/NCBI View Article : Google Scholar

129 

Lee P and Tan KS: Fusobacterium nucleatum activates the immune response through retinoic acid-inducible gene I. J Dent Res. 93:162–168. 2014.PubMed/NCBI View Article : Google Scholar

130 

Chaushu S, Wilensky A, Gur C, Shapira L, Elboim M, Halftek G, Polak D, Achdout H, Bachrach G and Mandelboim O: Direct recognition of Fusobacterium nucleatum by the NK cell natural cytotoxicity receptor NKp46 aggravates periodontal disease. PLoS Pathog. 8(e1002601)2012.PubMed/NCBI View Article : Google Scholar

131 

Huycke MM and Gaskins HR: Commensal bacteria, redox stress, and colorectal cancer Mechanisms and models. Exp Biol Med (Maywood). 229:586–597. 2004.PubMed/NCBI

132 

Rooks MG and Garrett WS: Bacteria, food, and cancer. F1000 Biol Rep 3. 12:2011.PubMed/NCBI View Article : Google Scholar

133 

Goodwin AC, Destefano Shields CE, Wu S, Huso DL, Wu X, Murray-Stewart TR, Hacker-Prietz A, Rabizadeh S, Woster PM, Sears CL, et al: Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis. Proc Natl Acad Sci USA. 108:15354–15359. 2011.PubMed/NCBI View Article : Google Scholar

134 

Arthur JC, Perez-Chanona E, Mühlbauer M, Tomkovich S, Uronis JM, Fan TJ, Campbell BJ, Abujamel T, Dogan B, Rogers AB, et al: Intestinal inflammation targets cancer-inducing activity of the microbiota. Science. 338:120–123. 2012.PubMed/NCBI View Article : Google Scholar

135 

Cougnoux A, Dalmasso G, Martinez R, Buc E, Delmas J, Gibold L, Sauvanet P, Darcha C, Déchelotte P, Bonnet M, et al: Bacterial genotoxin colibactin promotes colon tumour growth by inducing a senescence-associated secretory phenotype. Gut. 63:1932–1942. 2014.PubMed/NCBI View Article : Google Scholar

136 

Mangerich A, Knutson CG, Parry NM, Muthupalani S, Ye W, Prestwich E, Cui L, McFaline JL, Mobley M, Ge Z, et al: Infection-induced colitis in mice causes dynamic and tissue-specific changes in stress response and DNA damage leading to colon cancer. Proc Natl Acad Sci USA. 109:E1820–E1829. 2012.PubMed/NCBI View Article : Google Scholar

137 

Wang X, Allen TD, May RJ, Lightfoot S, Houchen CW and Huycke MM: Enterococcus faecalis induces aneuploidy and tetraploidy in colonic epithelial cells through a bystander effect. Cancer Res. 68:9909–9917. 2008.PubMed/NCBI View Article : Google Scholar

138 

Buc E, Dubois D, Sauvanet P, Raisch J, Delmas J, Darfeuille-Michaud A, Pezet D and Bonnet R: High prevalence of mucosa-associated Ecoli producing cyclomodulin and genotoxin in colon cancer. PLoS One. 8(e56964)2013.PubMed/NCBI View Article : Google Scholar

139 

Cuevas-Ramos G, Petit CR, Marcq I, Boury M, Oswald E and Nougayrède JP: Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells. Proc Natl Acad Sci USA. 107:11537–11542. 2010.PubMed/NCBI View Article : Google Scholar

140 

Devkota S, Wang Y, Musch MW, Leone V, Fehlner-Peach H, Nadimpalli A, Antonopoulos DA, Jabri B and Chang EB: Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in IL10-/- mice. Nature. 487:104–108. 2012.PubMed/NCBI View Article : Google Scholar

141 

Maggio-Price L, Treuting P, Zeng W, Tsang M, Bielefeldt-Ohmann H and Iritani BM: Helicobacter infection is required for inflammation and colon cancer in SMAD3-deficient mice. Cancer Res. 66:828–838. 2006.PubMed/NCBI View Article : Google Scholar

142 

Chu F-F, Esworthy RS, Chu PG, Longmate JA, Huycke MM, Wilczynski S and Doroshow JH: Bacteria-induced intestinal cancer in mice with disrupted Gpx1 and Gpx2 genes. Cancer Res. 64:962–968. 2004.PubMed/NCBI View Article : Google Scholar

143 

Ellmerich S, Schöller M, Duranton B, Gossé F, Galluser M, Klein JP and Raul F: Promotion of intestinal carcinogenesis by Streptococcus bovis. Carcinogenesis. 21:753–756. 2000.PubMed/NCBI

144 

Sheflin AM, Whitney AK and Weir TL: Cancer-promoting effects of microbial dysbiosis. Curr Oncol Rep. 16(406)2014.PubMed/NCBI View Article : Google Scholar

145 

Jobin C: Colorectal cancer: CRC - all about microbial products and barrier function? Nat Rev Gastroenterol Hepatol. 9:694–696. 2012.PubMed/NCBI View Article : Google Scholar

146 

Rao VP, Poutahidis T, Ge Z, Nambiar PR, Boussahmain C, Wang YY, Horwitz BH, Fox JG and Erdman SE: Innate immune inflammatory response against enteric bacteria Helicobacter hepaticus induces mammary adenocarcinoma in mice. Cancer Res. 66:7395–7400. 2006.PubMed/NCBI View Article : Google Scholar

147 

Reddy BS, Weisburger JH, Narisawa T and Wynder EL: Colon carcinogenesis in germ-free rats with 1,2-dimethylhydrazine and N-methyl-n'-nitro-N-nitrosoguanidine. Cancer Res. 34:2368–2372. 1974.PubMed/NCBI

148 

Reddy BS, Narisawa T, Wright P, Vukusich D, Weisburger JH and Wynder EL: Colon carcinogenesis with azoxymethane and dimethylhydrazine in germ-free rats. Cancer Res. 35:287–290. 1975.PubMed/NCBI

149 

Winter SE, Lopez CA and Bäumler AJ: The dynamics of gut-associated microbial communities during inflammation. EMBO Rep. 14:319–327. 2013.PubMed/NCBI View Article : Google Scholar

150 

Allen IC, TeKippe EM, Woodford RM, Uronis JM, Holl EK, Rogers AB, Herfarth HH, Jobin C and Ting JP: The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer. J Exp Med. 207:1045–1056. 2010.PubMed/NCBI View Article : Google Scholar

151 

Elinav E, Strowig T, Kau AL, Henao-Mejia J, Thaiss CA, Booth CJ, Peaper DR, Bertin J, Eisenbarth SC, Gordon JI, et al: NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell. 145:745–757. 2011.PubMed/NCBI View Article : Google Scholar

152 

Couturier-Maillard A, Secher T, Rehman A, Normand S, De Arcangelis A, Haesler R, Huot L, Grandjean T, Bressenot A, Delanoye-Crespin A, et al: NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer. J Clin Invest. 123:700–711. 2013.PubMed/NCBI View Article : Google Scholar

153 

Hu B, Elinav E, Huber S, Strowig T, Hao L, Hafemann A, Jin C, Wunderlich C, Wunderlich T, Eisenbarth SC, et al: Microbiota-induced activation of epithelial IL-6 signaling links inflammasome-driven inflammation with transmissible cancer. Proc Natl Acad Sci USA. 110:9862–9867. 2013.PubMed/NCBI View Article : Google Scholar

154 

Velcich A, Yang W, Heyer J, Fragale A, Nicholas C, Viani S, Kucherlapati R, Lipkin M, Yang K and Augenlicht L: Colorectal cancer in mice genetically deficient in the mucin Muc2. Science. 295:1726–1729. 2002.PubMed/NCBI View Article : Google Scholar

155 

Ochi A, Nguyen AH, Bedrosian AS, Mushlin HM, Zarbakhsh S, Barilla R, Zambirinis CP, Fallon NC, Rehman A, Pylayeva-Gupta Y, et al: MyD88 inhibition amplifies dendritic cell capacity to promote pancreatic carcinogenesis via Th2 cells. J Exp Med. 209:1671–1687. 2012.PubMed/NCBI View Article : Google Scholar

156 

Michaud DS, Joshipura K, Giovannucci E and Fuchs CS: A prospective study of periodontal disease and pancreatic cancer in US male health professionals. J Natl Cancer Inst. 99:171–175. 2007.PubMed/NCBI View Article : Google Scholar

157 

Farrell JJ, Zhang L, Zhou H, Chia D, Elashoff D, Akin D, Paster BJ, Joshipura K and Wong DT: Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer. Gut. 61:582–588. 2012.PubMed/NCBI View Article : Google Scholar

158 

Wiest R and Garcia-Tsao G: Bacterial translocation (BT) in cirrhosis. Hepatology. 41:422–433. 2005.PubMed/NCBI View Article : Google Scholar

159 

Seki E, De Minicis S, Osterreicher CH, Kluwe J, Osawa Y, Brenner DA and Schwabe RF: TLR4 enhances TGF-beta signaling and hepatic fibrosis. Nat Med. 13:1324–1332. 2007.PubMed/NCBI View Article : Google Scholar

160 

Yu LX, Yan HX, Liu Q, Yang W, Wu HP, Dong W, Tang L, Lin Y, He YQ, Zou SS, et al: Endotoxin accumulation prevents carcinogen-induced apoptosis and promotes liver tumorigenesis in rodents. Hepatology. 52:1322–1333. 2010.PubMed/NCBI View Article : Google Scholar

161 

Xuan C, Shamonki JM, Chung A, Dinome ML, Chung M, Sieling PA and Lee DJ: Microbial dysbiosis is associated with human breast cancer. PLoS One. 9(e83744)2014.PubMed/NCBI View Article : Google Scholar

162 

Velicer CM, Heckbert SR, Lampe JW, Potter JD, Robertson CA and Taplin SH: Antibiotic use in relation to the risk of breast cancer. JAMA. 291:827–835. 2004.PubMed/NCBI View Article : Google Scholar

163 

Wu S, Powell J, Mathioudakis N, Kane S, Fernandez E and Sears CL: Bacteroides fragilis enterotoxin induces intestinal epithelial cell secretion of interleukin-8 through mitogen-activated protein kinases and a tyrosine kinase-regulated nuclear factor-kappaB pathway. Infect Immun. 72:5832–5839. 2004.PubMed/NCBI View Article : Google Scholar

164 

Nougayrède JP, Taieb F, De Rycke J and Oswald E: Cyclomodulins: Bacterial effectors that modulate the eukaryotic cell cycle. Trends Microbiol. 13:103–110. 2005.PubMed/NCBI View Article : Google Scholar

165 

Nesić D, Hsu Y and Stebbins CE: Assembly and function of a bacterial genotoxin. Nature. 429:429–433. 2004.PubMed/NCBI View Article : Google Scholar

166 

Oswald E, Nougayrède JP, Taieb F and Sugai M: Bacterial toxins that modulate host cell-cycle progression. Curr Opin Microbiol. 8:83–91. 2005.PubMed/NCBI View Article : Google Scholar

167 

Travaglione S, Fabbri A and Fiorentini C: The Rho-activating CNF1 toxin from pathogenic E. coli: A risk factor for human cancer development? Infect Agent Cancer. 3(4)2008.PubMed/NCBI View Article : Google Scholar

168 

Fox JG and Wang TC: Inflammation, atrophy, and gastric cancer. J Clin Invest. 117:60–69. 2007.PubMed/NCBI View Article : Google Scholar

169 

Ohnishi N, Yuasa H, Tanaka S, Sawa H, Miura M, Matsui A, Higashi H, Musashi M, Iwabuchi K, Suzuki M, et al: Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. Proc Natl Acad Sci USA. 105:1003–1008. 2008.PubMed/NCBI View Article : Google Scholar

170 

Sears CL: Enterotoxigenic Bacteroides fragilis: A rogue among symbiotes. Clin Microbiol Rev. 22:349–369. 2009.PubMed/NCBI View Article : Google Scholar

171 

Wu S, Lim KC, Huang J, Saidi RF and Sears CL: Bacteroides fragilis enterotoxin cleaves the zonula adherens protein, E-cadherin. Proc Natl Acad Sci USA. 95:14979–14984. 1998.PubMed/NCBI

172 

Wu S, Shin J, Zhang G, Cohen M, Franco A and Sears CL: The Bacteroides fragilis toxin binds to a specific intestinal epithelial cell receptor. Infect Immun. 74:5382–5390. 2006.PubMed/NCBI View Article : Google Scholar

173 

Toprak NU, Yagci A, Gulluoglu BM, Akin ML, Demirkalem P, Celenk T and Soyletir G: A possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer. Clin Microbiol Infect. 12:782–786. 2006.PubMed/NCBI View Article : Google Scholar

174 

Wu S, Morin PJ, Maouyo D and Sears CL: Bacteroides fragilis enterotoxin induces c-Myc expression and cellular proliferation. Gastroenterology. 124:392–400. 2003.PubMed/NCBI View Article : Google Scholar

175 

Owen RW, Spiegelhalder B and Bartsch H: Generation of reactive oxygen species by the faecal matrix. Gut. 46:225–232. 2000.PubMed/NCBI View Article : Google Scholar

176 

Huycke MM, Abrams V and Moore DR: Enterococcus faecalis produces extracellular superoxide and hydrogen peroxide that damages colonic epithelial cell DNA. Carcinogenesis. 23:529–536. 2002.PubMed/NCBI

177 

Wallace JL: Hydrogen sulfide-releasing anti-inflammatory drugs. Trends Pharmacol Sci. 28:501–505. 2007.PubMed/NCBI View Article : Google Scholar

178 

Attene-Ramos MS, Wagner ED, Gaskins HR and Plewa MJ: Hydrogen sulfide induces direct radical-associated DNA damage. Mol Cancer Res. 5:455–459. 2007.PubMed/NCBI View Article : Google Scholar

179 

Le Gall T, Clermont O, Gouriou S, Picard B, Nassif X, Denamur E and Tenaillon O: Extraintestinal virulence is a coincidental by-product of commensalism in B2 phylogenetic group Escherichia coli strains. Mol Biol Evol. 24:2373–2384. 2007.PubMed/NCBI View Article : Google Scholar

180 

Escobar-Páramo P, Grenet K, Le Menac'h A, Rode L, Salgado E, Amorin C, Gouriou S, Picard B, Rahimy MC, Andremont A, et al: Large-scale population structure of human commensal Escherichia coli isolates. Appl Environ Microbiol. 70:5698–5700. 2004.PubMed/NCBI View Article : Google Scholar

181 

Darfeuille-Michaud A, Boudeau J, Bulois P, Neut C, Glasser AL, Barnich N, Bringer MA, Swidsinski A, Beaugerie L and Colombel JF: High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease. Gastroenterology. 127:412–421. 2004.PubMed/NCBI View Article : Google Scholar

182 

Han YW, Ikegami A, Rajanna C, Kawsar HI, Zhou Y, Li M, Sojar HT, Genco RJ, Kuramitsu HK and Deng CX: Identification and characterization of a novel adhesin unique to oral fusobacteria. J Bacteriol. 187:5330–5340. 2005.PubMed/NCBI View Article : Google Scholar

183 

Prorok-Hamon M, Friswell MK, Alswied A, Roberts CL, Song F, Flanagan PK, Knight P, Codling C, Marchesi JR, Winstanley C, et al: Colonic mucosa-associated diffusely adherent afaC+ Escherichia coli expressing lpfA and pks are increased in inflammatory bowel disease and colon cancer. Gut. 63:761–770. 2014.PubMed/NCBI View Article : Google Scholar

184 

Morrison DJ and Preston T: Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes. 7:189–200. 2016.PubMed/NCBI View Article : Google Scholar

185 

Belcheva A, Irrazabal T, Robertson SJ, Streutker C, Maughan H, Rubino S, Moriyama EH, Copeland JK, Surendra A, Kumar S, et al: Gut microbial metabolism drives transformation of MSH2-deficient colon epithelial cells. Cell. 158:288–299. 2014.PubMed/NCBI View Article : Google Scholar

186 

LeBlanc JG, Milani C, de Giori GS, Sesma F, van Sinderen D and Ventura M: Bacteria as vitamin suppliers to their host: A gut microbiota perspective. Curr Opin Biotechnol. 24:160–168. 2013.PubMed/NCBI View Article : Google Scholar

187 

Russell WR, Gratz SW, Duncan SH, Holtrop G, Ince J, Scobbie L, Duncan G, Johnstone AM, Lobley GE, Wallace RJ, et al: High-protein, reduced-carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health. Am J Clin Nutr. 93:1062–1072. 2011.PubMed/NCBI View Article : Google Scholar

188 

Windey K, De Preter V and Verbeke K: Relevance of protein fermentation to gut health. Mol Nutr Food Res. 56:184–196. 2012.PubMed/NCBI View Article : Google Scholar

189 

Neis EP, Dejong CH and Rensen SS: The role of microbial amino acid metabolism in host metabolism. Nutrients. 7:2930–2946. 2015.PubMed/NCBI View Article : Google Scholar

190 

Verbeke KA, Boobis AR, Chiodini A, Edwards CA, Franck A, Kleerebezem M, Nauta A, Raes J, van Tol EA and Tuohy KM: Towards microbial fermentation metabolites as markers for health benefits of prebiotics. Nutr Res Rev. 28:42–66. 2015.PubMed/NCBI View Article : Google Scholar

191 

Louis P, Hold GL and Flint HJ: The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev Microbiol. 12:661–672. 2014.PubMed/NCBI View Article : Google Scholar

192 

Donohoe DR, Garge N, Zhang X, Sun W, O'Connell TM, Bunger MK and Bultman SJ: The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab. 13:517–526. 2011.PubMed/NCBI View Article : Google Scholar

193 

Roediger WE: Role of anaerobic bacteria in the metabolic welfare of the colonic mucosa in man. Gut. 21:793–798. 1980.PubMed/NCBI View Article : Google Scholar

194 

Roediger WE: Utilization of nutrients by isolated epithelial cells of the rat colon. Gastroenterology. 83:424–429. 1982.PubMed/NCBI

195 

Sleeth ML, Thompson EL, Ford HE, Zac-Varghese SE and Frost G: Free fatty acid receptor 2 and nutrient sensing: A proposed role for fibre, fermentable carbohydrates and short-chain fatty acids in appetite regulation. Nutr Res Rev. 23:135–145. 2010.PubMed/NCBI View Article : Google Scholar

196 

Pessione E: Lactic acid bacteria contribution to gut microbiota complexity: Lights shadows. Front Cell Infect Microbiol. 2(86)2012.PubMed/NCBI View Article : Google Scholar

197 

Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ and Brummer RJ: Review article: The role of butyrate on colonic function. Aliment Pharmacol Ther. 27:104–119. 2008.PubMed/NCBI View Article : Google Scholar

198 

Fung KYC, Cosgrove L, Lockett T, Head R and Topping DL: A review of the potential mechanisms for the lowering of colorectal oncogenesis by butyrate. Br J Nutr. 108:820–831. 2012.PubMed/NCBI View Article : Google Scholar

199 

Wilson AJ, Chueh AC, Tögel L, Corner GA, Ahmed N, Goel S, Byun DS, Nasser S, Houston MA, Jhawer M, et al: Apoptotic sensitivity of colon cancer cells to histone deacetylase inhibitors is mediated by an Sp1/Sp3-activated transcriptional program involving immediate-early gene induction. Cancer Res. 70:609–620. 2010.PubMed/NCBI View Article : Google Scholar

200 

Chang PV, Hao L, Offermanns S and Medzhitov R: The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc Natl Acad Sci USA. 111:2247–2252. 2014.PubMed/NCBI View Article : Google Scholar

201 

Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly YM, Glickman JN and Garrett WS: The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 341:569–573. 2013.PubMed/NCBI View Article : Google Scholar

202 

Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, Takahashi D, Nakanishi Y, Uetake C, Kato K, Kato T, et al: Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 504:446–450. 2013.PubMed/NCBI View Article : Google Scholar

203 

Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, Liu H, Cross JR, Pfeffer K, Coffer PJ, et al: Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 504:451–455. 2013.PubMed/NCBI View Article : Google Scholar

204 

Vander Heiden MG, Cantley LC and Thompson CB: Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science. 324:1029–1033. 2009.PubMed/NCBI View Article : Google Scholar

205 

Donohoe DR, Holley D, Collins LB, Montgomery SA, Whitmore AC, Hillhouse A, Curry KP, Renner SW, Greenwalt A, Ryan EP, et al: A gnotobiotic mouse model demonstrates that dietary fiber protects against colorectal tumorigenesis in a microbiota- and butyrate-dependent manner. Cancer Discov. 4:1387–1397. 2014.PubMed/NCBI View Article : Google Scholar

206 

Donohoe DR, Collins LB, Wali A, Bigler R, Sun W and Bultman SJ: The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. Mol Cell. 48:612–626. 2012.PubMed/NCBI View Article : Google Scholar

207 

Sebastián C and Mostoslavsky R: Untangling the fiber yarn: Butyrate feeds Warburg to suppress colorectal cancer. Cancer Discov. 4:1368–1370. 2014.PubMed/NCBI View Article : Google Scholar

208 

Davie JR: Inhibition of histone deacetylase activity by butyrate. J Nutr. 133((Suppl 7)): 2485S–2493S. 2003.PubMed/NCBI View Article : Google Scholar

209 

Gonçalves P and Martel F: Butyrate and colorectal cancer: The role of butyrate transport. Curr Drug Metab. 14:994–1008. 2013.PubMed/NCBI View Article : Google Scholar

210 

Thangaraju M, Cresci GA, Liu K, Ananth S, Gnanaprakasam JP, Browning DD, Mellinger JD, Smith SB, Digby GJ, Lambert NA, et al: GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. Cancer Res. 69:2826–2832. 2009.PubMed/NCBI View Article : Google Scholar

211 

Singh N, Gurav A, Sivaprakasam S, Brady E, Padia R, Shi H, Thangaraju M, Prasad PD, Manicassamy S, Munn DH, et al: Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity. 40:128–139. 2014.PubMed/NCBI View Article : Google Scholar

212 

Larrosa M, González-Sarrías A, García-Conesa MT, Tomás-Barberán FA and Espín JC: Urolithins, ellagic acid-derived metabolites produced by human colonic microflora, exhibit estrogenic and antiestrogenic activities. J Agric Food Chem. 54:1611–1620. 2006.PubMed/NCBI View Article : Google Scholar

213 

González-Sarrías A, Larrosa M, Tomás-Barberán FA, Dolara P and Espín JC: NF-kappaB-dependent anti-inflammatory activity of urolithins, gut microbiota ellagic acid-derived metabolites, in human colonic fibroblasts. Br J Nutr. 104:503–512. 2010.PubMed/NCBI View Article : Google Scholar

214 

Atkinson C, Frankenfeld CL and Lampe JW: Gut bacterial metabolism of the soy isoflavone daidzein: Exploring the relevance to human health. Exp Biol Med (Maywood). 230:155–170. 2005.PubMed/NCBI

215 

Bolca S, Possemiers S, Herregat A, Huybrechts I, Heyerick A, De Vriese S, Verbruggen M, Depypere H, De Keukeleire D, Bracke M, et al: Microbial and dietary factors are associated with the equol producer phenotype in healthy postmenopausal women. J Nutr. 137:2242–2246. 2007.PubMed/NCBI View Article : Google Scholar

216 

Lampe JW: Emerging research on equol cancer. J Nutr. 140:1369S–1372S. 2010.PubMed/NCBI View Article : Google Scholar

217 

Davis CD and Milner JA: Gastrointestinal microflora, food components and colon cancer prevention. J Nutr Biochem. 20:743–752. 2009.PubMed/NCBI View Article : Google Scholar

218 

Bode LM, Bunzel D, Huch M, Cho GS, Ruhland D, Bunzel M, Bub A, Franz CM and Kulling SE: In vivo and in vitro metabolism of trans-resveratrol by human gut microbiota. Am J Clin Nutr. 97:295–309. 2013.PubMed/NCBI View Article : Google Scholar

219 

Greer JB and O'Keefe SJ: Microbial induction of immunity, inflammation, and cancer. Front Physiol. 1(168)2011.PubMed/NCBI View Article : Google Scholar

220 

Ridlon JM, Kang DJ and Hylemon PB: Bile salt biotransformations by human intestinal bacteria. J Lipid Res. 47:241–259. 2006.PubMed/NCBI View Article : Google Scholar

221 

Wells JE, Williams KB, Whitehead TR, Heuman DM and Hylemon PB: Development and application of a polymerase chain reaction assay for the detection and enumeration of bile acid 7alpha-dehydroxylating bacteria in human feces. Clin Chim Acta. 331:127–134. 2003.PubMed/NCBI View Article : Google Scholar

222 

Rubin DC, Shaker A and Levin MS: Chronic intestinal inflammation: Inflammatory bowel disease and colitis-associated colon cancer. Front Immunol. 3(107)2012.PubMed/NCBI View Article : Google Scholar

223 

Powolny A, Xu J and 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. 33:193–203. 2001.PubMed/NCBI View Article : Google Scholar

224 

Imray CH, Radley S, Davis A, Barker G, Hendrickse CW, Donovan IA, Lawson AM, Baker PR and Neoptolemos JP: Faecal unconjugated bile acids in patients with colorectal cancer or polyps. Gut. 33:1239–1245. 1992.PubMed/NCBI View Article : Google Scholar

225 

Nagengast FM, Grubben MJ and van Munster IP: Role of bile acids in colorectal carcinogenesis. Eur J Cancer. 31A:1067–1070. 1995.PubMed/NCBI View Article : Google Scholar

226 

Carmody RN and Turnbaugh PJ: Host-microbial interactions in the metabolism of therapeutic and diet-derived xenobiotics. J Clin Invest. 124:4173–4181. 2014.PubMed/NCBI View Article : Google Scholar

227 

Flanagan L, Schmid J, Ebert M, Soucek P, Kunicka T, Liska V, Bruha J, Neary P, Dezeeuw N, Tommasino M, et al: Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome. Eur J Clin Microbiol Infect Dis. 33:1381–1390. 2014.PubMed/NCBI View Article : Google Scholar

228 

McCoy AN, Araújo-Pérez F, Azcárate-Peril A, Yeh JJ, Sandler RS and Keku TO: Fusobacterium is associated with colorectal adenomas. PLoS One. 8(e53653)2013.PubMed/NCBI View Article : Google Scholar

229 

Fukugaiti MH, Ignacio A, Fernandes MR, Ribeiro Júnior U, Nakano V and Avila-Campos MJ: High occurrence of Fusobacterium nucleatum and Clostridium difficile in the intestinal microbiota of colorectal carcinoma patients. Braz J Microbiol. 46:1135–1140. 2015.PubMed/NCBI View Article : Google Scholar

230 

Zackular JP, Rogers MAM, Ruffin MT IV and Schloss PD: The human gut microbiome as a screening tool for colorectal cancer. Cancer Prev Res (Phila). 7:1112–1121. 2014.PubMed/NCBI View Article : Google Scholar

231 

Mima K, Nishihara R, Qian ZR, Cao Y, Sukawa Y, Nowak JA, Yang J, Dou R, Masugi Y, Song M, et al: Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis. Gut. 65:1973–1980. 2016.PubMed/NCBI View Article : Google Scholar

232 

Ballal SA, Veiga P, Fenn K, Michaud M, Kim JH, Gallini CA, Glickman JN, Quéré G, Garault P, Béal C, et al: Host lysozyme-mediated lysis of Lactococcus lactis facilitates delivery of colitis-attenuating superoxide dismutase to inflamed colons. Proc Natl Acad Sci USA. 112:7803–7808. 2015.PubMed/NCBI View Article : Google Scholar

233 

Veiga P, Gallini CA, Beal C, Michaud M, Delaney ML, DuBois A, Khlebnikov A, van Hylckama Vlieg JE, Punit S, Glickman JN, et al: Bifidobacterium animalis subsplactis fermented milk product reduces inflammation by altering a niche for colitogenic microbes. Proc Natl Acad Sci USA. 107:18132–18137. 2010.PubMed/NCBI View Article : Google Scholar

234 

Viaud S, Saccheri F, Mignot G, Yamazaki T, Daillère R, Hannani D, Enot DP, Pfirschke C, Engblom C, Pittet MJ, et al: The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science. 342:971–976. 2013.PubMed/NCBI View Article : Google Scholar

235 

Siddik ZH: Cisplatin: Mode of cytotoxic action and molecular basis of resistance. Oncogene. 22:7265–7279. 2003.PubMed/NCBI View Article : Google Scholar

236 

Yang J, Liu KX, Qu JM and Wang XD: The changes induced by cyclophosphamide in intestinal barrier and microflora in mice. Eur J Pharmacol. 714:120–124. 2013.PubMed/NCBI View Article : Google Scholar

237 

Nam YD, Kim HJ, Seo JG, Kang SW and Bae JW: Impact of pelvic radiotherapy on gut microbiota of gynecological cancer patients revealed by massive pyrosequencing. PLoS One. 8(e82659)2013.PubMed/NCBI View Article : Google Scholar

238 

Jenq RR, Ubeda C, Taur Y, Menezes CC, Khanin R, Dudakov JA, Liu C, West ML, Singer NV, Equinda MJ, et al: Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. J Exp Med. 209:903–911. 2012.PubMed/NCBI View Article : Google Scholar

239 

Von Bültzingslöwen I, Adlerberth I, Wold AE, Dahlén G and Jontell M: Oral and intestinal microflora in 5-fluorouracil treated rats, translocation to cervical and mesenteric lymph nodes and effects of probiotic bacteria. Oral Microbiol Immunol. 18:278–284. 2003.PubMed/NCBI View Article : Google Scholar

240 

Wallace BD, Wang H, Lane KT, Scott JE, Orans J, Koo JS, Venkatesh M, Jobin C, Yeh LA, Mani S, et al: Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science. 330:831–835. 2010.PubMed/NCBI View Article : Google Scholar

241 

Lam W, Bussom S, Guan F, Jiang Z, Zhang W, Gullen EA, Liu SH and Cheng YC: The four-herb Chinese medicine PHY906 reduces chemotherapy-induced gastrointestinal toxicity. Sci Transl Med. 2(45ra59)2010.PubMed/NCBI View Article : Google Scholar

242 

Cesaro C, Tiso A, Del Prete A, Cariello R, Tuccillo C, Cotticelli G, Del Vecchio Blanco C and Loguercio C: Gut microbiota and probiotics in chronic liver diseases. Dig Liver Dis. 43:431–438. 2011.PubMed/NCBI View Article : Google Scholar

243 

Hemarajata P and Versalovic J: Effects of probiotics on gut microbiota: Mechanisms of intestinal immunomodulation and neuromodulation. Therap Adv Gastroenterol. 6:39–51. 2013.PubMed/NCBI View Article : Google Scholar

244 

Ekmekciu I, von Klitzing E, Fiebiger U, Neumann C, Bacher P, Scheffold A, Bereswill S and Heimesaat MM: The probiotic compound VSL#3 modulates mucosal, peripheral, and systemic immunity following murine broad-spectrum antibiotic treatment. Front Cell Infect Microbiol. 7(167)2017.PubMed/NCBI View Article : Google Scholar

245 

Rao RK and Samak G: Protection and restitution of gut barrier by probiotics Nutritional and clinical implications. Curr Nutr Food Sci. 9:99–107. 2013.PubMed/NCBI

246 

Kamada N, Chen GY, Inohara N and Núñez G: Control of pathogens and pathobionts by the gut microbiota. Nat Immunol. 14:685–690. 2013.PubMed/NCBI View Article : Google Scholar

247 

Jonkers D and Stockbrügger R: Probiotics and inflammatory bowel disease. J R Soc Med. 96:167–171. 2003.PubMed/NCBI

248 

Celiberto LS, Bedani R, Rossi EA and Cavallini DC: Probiotics: The scientific evidence in the context of inflammatory bowel disease. Crit Rev Food Sci Nutr. 57:1759–1768. 2017.PubMed/NCBI View Article : Google Scholar

249 

Sheil B, Shanahan F and O'Mahony L: Probiotic effects on inflammatory bowel disease. J Nutr. 137:(Suppl 2):819S–824S. 2007.PubMed/NCBI View Article : Google Scholar

250 

Tamboli CP, Caucheteux C, Cortot A, Colombel JF and Desreumaux P: Probiotics in inflammatory bowel disease: A critical review. Best Pract Res Clin Gastroenterol. 17:805–820. 2003.PubMed/NCBI View Article : Google Scholar

251 

Bibiloni R, Fedorak RN, Tannock GW, Madsen KL, Gionchetti P, Campieri M, De Simone C and Sartor RB: VSL#3 probiotic-mixture induces remission in patients with active ulcerative colitis. Am J Gastroenterol. 100:1539–1546. 2005.PubMed/NCBI View Article : Google Scholar

252 

Kim S, Covington A and Pamer EG: The intestinal microbiota: Antibiotics, colonization resistance, and enteric pathogens. Immunol Rev. 279:90–105. 2017.PubMed/NCBI View Article : Google Scholar

253 

Dethlefsen L, Huse S, Sogin ML and Relman DA: The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol. 6(e280)2008.PubMed/NCBI View Article : Google Scholar

254 

Dethlefsen L and Relman DA: Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci USA. 108((Suppl 1)): 4554–4561. 2011.PubMed/NCBI View Article : Google Scholar

255 

Jernberg C, Löfmark S, Edlund C and Jansson JK: Long-term ecological impacts of antibiotic administration on the human intestinal microbiota. ISME J. 1:56–66. 2007.PubMed/NCBI View Article : Google Scholar

256 

Lankelma JM, Cranendonk DR, Belzer C, de Vos AF, de Vos WM, van der Poll T and Wiersinga WJ: Antibiotic-induced gut microbiota disruption during human endotoxemia: A randomised controlled study. Gut. 66:1623–1630. 2017.PubMed/NCBI View Article : Google Scholar

257 

Lopez J and Grinspan A: Fecal microbiota transplantation for inflammatory bowel disease. Gastroenterol Hepatol (NY). 12:374–379. 2016.PubMed/NCBI

258 

McFarland LV: Epidemiology, risk factors and treatments for antibiotic-associated diarrhea. Dig Dis. 16:292–307. 1998.PubMed/NCBI View Article : Google Scholar

259 

Suez J, Zmora N, Zilberman-Schapira G, Mor U, Dori-Bachash M, Bashiardes S, Zur M, Regev-Lehavi D, Ben-Zeev Brik R, Federici S, et al: Post-antibiotic gut mucosal microbiome reconstitution is impaired by probiotics and improved by autologous FMT. Cell. 174:1406–1423, e16. 2018.PubMed/NCBI View Article : Google Scholar

260 

Chaput N, Lepage P, Coutzac C, Soularue E, Le Roux K, Monot C, Boselli L, Routier E, Cassard L, Collins M, et al: Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. Ann Oncol. 28:1368–1379. 2017.PubMed/NCBI View Article : Google Scholar

261 

Frankel AE, Coughlin LA, Kim J, Froehlich TW, Xie Y, Frenkel EP and Koh AY: 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. 2017.PubMed/NCBI View Article : Google Scholar

262 

Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, Prieto PA, Vicente D, Hoffman K, Wei SC, et al: Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 359:97–103. 2018.PubMed/NCBI View Article : Google Scholar

263 

Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre ML, Luke JJ and Gajewski TF: The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 359:104–108. 2018.PubMed/NCBI View Article : Google Scholar

264 

Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP, et al: Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 359:91–97. 2018.PubMed/NCBI View Article : Google Scholar

265 

Vétizou M, Pitt JM, Daillère R, Lepage P, Waldschmitt N, Flament C, Rusakiewicz S, Routy B, Roberti MP, Duong CP, et al: Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 350:1079–1084. 2015.PubMed/NCBI View Article : Google Scholar

266 

Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, Benyamin FW, Lei YM, Jabri B, Alegre ML, et al: Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 350:1084–1089. 2015.PubMed/NCBI View Article : Google Scholar

Related Articles

Journal Cover

January 2019
Volume 1 Issue 1

Print ISSN: 2632-2900
Online ISSN:2632-2919

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Baliou, S., Adamaki, M., Spandidos, D.A., Kyriakopoulos, A.M., Christodoulou, I., & Zoumpourlis, V. (2019). The microbiome, its molecular mechanisms and its potential as a therapeutic strategy against colorectal carcinogenesis (Review). World Academy of Sciences Journal, 1, 3-19. https://doi.org/10.3892/wasj.2018.6
MLA
Baliou, S., Adamaki, M., Spandidos, D. A., Kyriakopoulos, A. M., Christodoulou, I., Zoumpourlis, V."The microbiome, its molecular mechanisms and its potential as a therapeutic strategy against colorectal carcinogenesis (Review)". World Academy of Sciences Journal 1.1 (2019): 3-19.
Chicago
Baliou, S., Adamaki, M., Spandidos, D. A., Kyriakopoulos, A. M., Christodoulou, I., Zoumpourlis, V."The microbiome, its molecular mechanisms and its potential as a therapeutic strategy against colorectal carcinogenesis (Review)". World Academy of Sciences Journal 1, no. 1 (2019): 3-19. https://doi.org/10.3892/wasj.2018.6