1. Miller KD, Nogueira L, Mariotto AB, et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin 2019;Sep;69:363–385.

2. Siegel RL, Miller KD, Fedewa SA, et al. Colorectal cancer statistics, 2017. CA Cancer J Clin 2017;67:177–193.

3. Miller K. Excellent care for cancer survivors: a guide to fully meet their needs in medical offices and in the community. Santa Barbara: ABC-CLIO, 2012. 4. Sender R, Fuchs S, Milo R. Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell 2016;164:337–340.

5. Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI. Human nutrition, the gut microbiome and the immune system. Nature 2011;474:327–336.

6. Nicholson JK, Holmes E, Kinross J, et al. Host-gut microbiota metabolic interactions. Science 2012;336:1262–1267.

7. Wilson ID, Nicholson JK. Gut microbiome interactions with drug metabolism, efficacy, and toxicity. Transl Res 2017;179:204–222.

8. Barko PC, McMichael MA, Swanson KS, Williams DA. The gastrointestinal microbiome: a review. J Vet Intern Med 2018;32:9–25.

9. Rescigno M, Urbano M, Valzasina B, et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2001;2:361–367.

10. Ostman S, Rask C, Wold AE, Hultkrantz S, Telemo E. Impaired regulatory T cell function in germ-free mice. Eur J Immunol 2006;36:2336–2346.

11. Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell 2008;133:775–787.

12. Josefowicz SZ, Niec RE, Kim HY, et al. Extrathymically generated regulatory T cells control mucosal TH2 inflammation. Nature 2012;482:395–399.

13. Mucida D, Kutchukhidze N, Erazo A, Russo M, Lafaille JJ, Curotto de Lafaille MA. Oral tolerance in the absence of naturally occurring Tregs. J Clin Invest 2005;115:1923–1933.

14. Mazmanian SK, Round JL, Kasper DL. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 2008;453:620–625.

15. Round JL, Lee SM, Li J, et al. The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science 2011;332:974–977.

16. Rabizadeh S, Rhee KJ, Wu S, et al. Enterotoxigenic Bacteroides fragilis: a potential instigator of colitis. Inflamm Bowel Dis 2007;13:1475–1483.

17. Wu S, Rhee KJ, Albesiano E, et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med 2009;15:1016–1022.

18. Langrish CL, Chen Y, Blumenschein WM, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 2005;201:233–240.

19. Zhang GX, Gran B, Yu S, et al. Induction of experimental autoimmune encephalomyelitis in IL-12 receptor-beta 2-deficient mice: IL-12 responsiveness is not required in the pathogenesis of inflammatory demyelination in the central nervous system. J Immunol 2003;170:2153–2160.

20. Koenen HJ, Smeets RL, Vink PM, van Rijssen E, Boots AM, Joosten I. Human CD25highFoxp3pos regulatory T cells differentiate into IL-17-producing cells. Blood 2008;112:2340–2352.

21. Osorio F, LeibundGut-Landmann S, Lochner M, et al. DC activated via dectin-1 convert Treg into IL-17 producers. Eur J Immunol 2008;38:3274–3281.

22. Xu L, Kitani A, Fuss I, Strober W. Cutting edge: regulatory T cells induce CD4+CD25-Foxp3- T cells or are self-induced to become Th17 cells in the absence of exogenous TGF-beta. J Immunol 2007;178:6725–6729.

23. Yang XO, Nurieva R, Martinez GJ, et al. Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 2008;29:44–56.

24. Gaboriau-Routhiau V, Rakotobe S, Lécuyer E, et al. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 2009;31:677–689.

25. Wang Y, Yin Y, Chen X, et al. Induction of intestinal Th17 cells by flagellins from segmented filamentous bacteria. Front Immunol 2019;10:2750.

26. Cummings JH, Pomare EW, Branch WJ, Naylor CP, Macfarlane GT. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 1987;28:1221–1227.

27. Furusawa Y, Obata Y, Fukuda S, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 2013;504:446–450.

28. McDermott AJ, Huffnagle GB. The microbiome and regulation of mucosal immunity. Immunology 2014;142:24–31.

29. Di Giacinto C, Marinaro M, Sanchez M, Strober W, Boirivant M. Probiotics ameliorate recurrent Th1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-beta-bearing regulatory cells. J Immunol 2005;174:3237–3246.

30. Feleszko W, Jaworska J, Rha RD, et al. Probiotic-induced suppression of allergic sensitization and airway inflammation is associated with an increase of T regulatory-dependent mechanisms in a murine model of asthma. Clin Exp Allergy 2007;37:498–505.

31. Chen GY. The role of the gut microbiome in colorectal cancer. Clin Colon Rectal Surg 2018;31:192–198.

32. Park CH, Eun CS, Han DS. Intestinal microbiota, chronic inflammation, and colorectal cancer. Intest Res 2018;16:338–345.

33. Gagnière J, Raisch J, Veziant J, et al. Gut microbiota imbalance and colorectal cancer. World J Gastroenterol 2016;22:501–518.

34. Yu LC, Wei SC, Ni YH. Impact of microbiota in colorectal carcinogenesis: lessons from experimental models. Intest Res 2018;16:346–357.

35. Feng Q, Liang S, Jia H, et al. Gut microbiome development along the colorectal adenoma-carcinoma sequence. Nat Commun 2015;6:6528.

36. Arthur JC, Perez-Chanona E, Mühlbauer M, et al. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 2012;338:120–123.

37. Purcell RV, Pearson J, Aitchison A, Dixon L, Frizelle FA, Keenan JI. Colonization with enterotoxigenic Bacteroides fragilis is associated with early-stage colorectal neoplasia. PLoS One 2017;12:e0171602.

38. Bonnet M, Buc E, Sauvanet P, et al. Colonization of the human gut by E. coli and colorectal cancer risk. Clin Cancer Res 2014;20:859–867.

39. Raisch J, Buc E, Bonnet M, et al. Colon cancer-associated B2 Escherichia coli colonize gut mucosa and promote cell proliferation. World J Gastroenterol 2014;20:6560–6572.

40. Nougayrède JP, Homburg S, Taieb F, et al. Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science 2006;313:848–851.

41. Secher T, Samba-Louaka A, Oswald E, Nougayrède JP. Escherichia coli producing colibactin triggers premature and transmissible senescence in mammalian cells. PLoS One 2013;8:e77157.

42. Cougnoux A, Dalmasso G, Martinez R, et al. Bacterial genotoxin colibactin promotes colon tumour growth by inducing a senescence-associated secretory phenotype. Gut 2014;63:1932–1942.

43. Marchès O, Ledger TN, Boury M, et al. Enteropathogenic and enterohaemorrhagic Escherichia coli deliver a novel effector called Cif, which blocks cell cycle G2/M transition. Mol Microbiol 2003;50:1553–1567.

44. Maddocks OD, Short AJ, Donnenberg MS, Bader S, Harrison DJ. Attaching and effacing Escherichia coli downregulate DNA mismatch repair protein in vitro and are associated with colorectal adenocarcinomas in humans. PLoS One 2009;4:e5517.

45. Nowrouzian FL, Oswald E. Escherichia coli strains with the capacity for long-term persistence in the bowel microbiota carry the potentially genotoxic pks island. Microb Pathog 2012;53:180–182.

46. 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 U S A 2010;107:11537–115342.

47. Hussan H, Clinton SK, Roberts K, Bailey MT. Fusobacterium’s link to colorectal neoplasia sequenced: a systematic review and future insights. World J Gastroenterol 2017;23:8626–8650.

48. Kostic AD, Chun E, Robertson L, et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 2013;14:207–215.

49. Bachrach G, Ianculovici C, Naor R, Weiss EI. Fluorescence based measurements of Fusobacterium nucleatum coaggregation and of fusobacterial attachment to mammalian cells. FEMS Microbiol Lett 2005;248:235–240.

50. Gur C, Ibrahim Y, Isaacson B, et al. Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. Immunity 2015;42:344–355.

51. Mima K, Nishihara R, Qian ZR, et al. Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis. Gut 2016;65:1973–1980.

52. Brennan CA, Garrett WS. Fusobacterium nucleatum: symbiont, opportunist and oncobacterium. Nat Rev Microbiol 2019;17:156–166.

53. Sánchez B, Delgado S, Blanco-Míguez A, Lourenço A, Gueimonde M, Margolles A. Probiotics, gut microbiota, and their influence on host health and disease. Mol Nutr Food Res 2017;61:1600240.

54. Alexander JL, Wilson ID, Teare J, Marchesi JR, Nicholson JK, Kinross JM. Gut microbiota modulation of chemotherapy efficacy and toxicity. Nat Rev Gastroenterol Hepatol 2017;14:356–365.

55. Heydari Z, Rahaie M, Alizadeh AM, Agah S, Khalighfard S, Bahmani S. Effects of Lactobacillus acidophilus and Bifidobacterium bifidum probiotics on the expression of microRNAs 135b, 26b, 18a and 155, and their involving genes in mice colon cancer. Probiotics Antimicrob Proteins 2019;11:1155–1162.

56. Baldwin C, Millette M, Oth D, Ruiz MT, Luquet FM, Lacroix M. Probiotic Lactobacillus acidophilus and L. casei mix sensitize colorectal tumoral cells to 5-fluorouracil-induced apoptosis. Nutr Cancer 2010;62:371–378.

57. Dos Reis SA, da Conceição LL, Siqueira NP, Rosa DD, da Silva LL, Peluzio MD. Review of the mechanisms of probiotic actions in the prevention of colorectal cancer. Nutr Res 2017;37:1–19.

58. Escamilla J, Lane MA, Maitin V. Cell-free supernatants from probiotic Lactobacillus casei and Lactobacillus rhamnosus GG decrease colon cancer cell invasion in vitro. Nutr Cancer 2012;64:871–878.

59. Soltan Dallal MM, Mojarrad M, Baghbani F, Raoofian R, Mardaneh J, Salehipour Z. Effects of probiotic Lactobacillus acidophilus and Lactobacillus casei on colorectal tumor cells activity (CaCo-2). Arch Iran Med 2015;18:167–172.

60. An J, Ha EM. Combination therapy of Lactobacillus plantarum supernatant and 5-fluouracil increases chemosensitivity in colorectal cancer cells. J Microbiol Biotechnol 2016;26:1490–1503.

61. Saber A, Alipour B, Faghfoori Z, Mousavi Jam A, Yari Khosroushahi A. Secretion metabolites of probiotic yeast, Pichia kudriavzevii AS-12, induces apoptosis pathways in human colorectal cancer cell lines. Nutr Res 2017;41:36–46.

62. Mi H, Dong Y, Zhang B, et al. Bifidobacterium infantis ameliorates chemotherapy-induced intestinal mucositis via regulating T cell immunity in colorectal cancer rats. Cell Physiol Biochem 2017;42:2330–2341.

63. Osterlund P, Ruotsalainen T, Korpela R, et al. Lactobacillus supplementation for diarrhoea related to chemotherapy of colorectal cancer: a randomised study. Br J Cancer 2007;97:1028–1034.

64. Golkhalkhali B, Rajandram R, Paliany AS, et al. Strain-specific probiotic (microbial cell preparation) and omega-3 fatty acid in modulating quality of life and inflammatory markers in colorectal cancer patients: a randomized controlled trial. Asia Pac J Clin Oncol 2018;14:179–191.

65. Mego M, Chovanec J, Vochyanova-Andrezalova I, et al. Prevention of irinotecan induced diarrhea by probiotics: a randomized double blind, placebo controlled pilot study. Complement Ther Med 2015;23:356–362.

66. Aisu N, Tanimura S, Yamashita Y, et al. Impact of perioperative probiotic treatment for surgical site infections in patients with colorectal cancer. Exp Ther Med 2015;10:966–972.

67. Yang Y, Xia Y, Chen H, et al. The effect of perioperative probiotics treatment for colorectal cancer: short-term outcomes of a randomized controlled trial. Oncotarget 2016;7:8432–8440.

68. Chen ZY, Hsieh YM, Huang CC, Tsai CC. Inhibitory effects of probiotic Lactobacillus on the growth of human colonic carcinoma cell line HT-29. Molecules 2017;22:107.

69. Martín R, Langella P. Emerging health concepts in the probiotics field: streamlining the definitions. Front Microbiol 2019;10:1047.

70. Chang CJ, Lin TL, Tsai YL, et al. Next generation probiotics in disease amelioration. J Food Drug Anal 2019;27:615–622.

71. Wang Y, Ma R, Liu F, Lee SA, Zhang L. Modulation of gut microbiota: a novel paradigm of enhancing the efficacy of programmed death-1 and programmed death ligand-1 blockade therapy. Front Immunol 2018;9:374.

72. Cani PD, de Vos WM. Next-generation beneficial microbes: the case of Akkermansia muciniphila. Front Microbiol 2017;8:1765.

73. Guthrie L, Gupta S, Daily J, Kelly L. Human microbiome signatures of differential colorectal cancer drug metabolism. NPJ Biofilms Microbiomes 2017;3:27.

74. Wallace BD, Wang H, Lane KT, et al. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science 2010;330:831–835.

75. Wang J, Feng W, Zhang S, et al. Gut microbial modulation in the treatment of chemotherapy-induced diarrhea with Shenzhu Capsule. BMC Complement Altern Med 2019;19:126.

76. Wang YH, Yao N, Wei KK, et al. The efficacy and safety of probiotics for prevention of chemoradiotherapy-induced diarrhea in people with abdominal and pelvic cancer: a systematic review and meta-analysis. Eur J Clin Nutr 2016;70:1246–1253.

77. Serna-Thomé G, Castro-Eguiluz D, Fuchs-Tarlovsky V, et al. Use of functional foods and oral supplements as adjuvants in cancer treatment. Rev Invest Clin 2018;70:136–146.

78. Tan CK, Said S, Rajandram R, Wang Z, Roslani AC, Chin KF. Pre-surgical administration of microbial cell preparation in colorectal cancer patients: a randomized controlled trial. World J Surg 2016;40:1985–1992.

79. Kotzampassi K, Stavrou G, Damoraki G, et al. A four-probiotics regimen reduces postoperative complications after colorectal surgery: a randomized, double-blind, placebo-controlled study. World J Surg 2015;39:2776–2783.

80. Liu ZH, Huang MJ, Zhang XW, et al. The effects of perioperative probiotic treatment on serum zonulin concentration and subsequent postoperative infectious complications after colorectal cancer surgery: a double-center and double-blind randomized clinical trial. Am J Clin Nutr 2013;97:117–126.

81. Xie X, He Y, Li H, et al. Effects of prebiotics on immunologic indicators and intestinal microbiota structure in perioperative colorectal cancer patients. Nutrition 2019;61:132–142.

82. Bruno-Barcena JM, Azcarate-Peril MA. Galacto-oligosaccharides and colorectal cancer: feeding our intestinal probiome. J Funct Foods 2015;12:92–108.

83. Kuugbee ED, Shang X, Gamallat Y, et al. Structural change in microbiota by a probiotic cocktail enhances the gut barrier and reduces cancer via TLR2 signaling in a rat model of colon cancer. Dig Dis Sci 2016;61:2908–2920.

84. Saito Y, Hinoi T, Adachi T, et al. Synbiotics suppress colitis-induced tumorigenesis in a colon-specific cancer mouse model. PLoS One 2019;14:e0216393.

85. Rafter J, Bennett M, Caderni G, et al. Dietary synbiotics reduce cancer risk factors in polypectomized and colon cancer patients. Am J Clin Nutr 2007;85:488–496.

86. de Moura NA, Caetano BF, Sivieri K, et al. Protective effects of yacon (Smallanthus sonchifolius) intake on experimental colon carcinogenesis. Food Chem Toxicol 2012;50:2902–2910.

87. Gavresea F, Vagianos C, Korontzi M, et al. Beneficial effect of synbiotics on experimental colon cancer in rats. Turk J Gastroenterol 2018;29:494–501.

88. Li Y, Elmén L, Segota I, et al. Prebiotic-induced anti-tumor immunity attenuates tumor growth. Cell Rep 2020;30:1753–1766.

89. Lee CW, Chen HJ, Chien YH, Hsia SM, Chen JH, Shih CK. Synbiotic combination of djulis (Chenopodium formosanum) and Lactobacillus acidophilus inhibits colon carcinogenesis in rats. Nutrients 2019;12:103.

90. Krebs B. Prebiotic and synbiotic treatment before colorectal surgery: randomised double blind trial. Coll Antropol 2016;40:35–40.