Microbes and cancer

Annual Review of Immunology

Volumn 35, Issue , 2017, Pages 199-228

  Dzutsev, Amiran ^a   Badger, Jonathan H ^a   Perez Chanona, Ernesto ^a   Roy, Soumen ^a   Salcedo, Rosalba ^a   Smith, Carolyne K ^a   Trinchieri, Giorgio ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Cachexia; Cancer; Carcinogenesis; Chemotherapy; Immunotherapy; Metabolism and cancer; Microbiota

Indexed keywords

CANCER CHEMOTHERAPY; CANCER IMMUNOTHERAPY; CANCER THERAPY; CARCINOGENICITY; COMORBIDITY; HOMEOSTASIS; HUMAN; IMMUNE RESPONSE; INTESTINE FLORA; MALIGNANT NEOPLASM; MICROFLORA; MICROORGANISM; NONHUMAN; OBESITY; PRIORITY JOURNAL; REVIEW; ADAPTIVE IMMUNITY; ANIMAL; CARCINOGENESIS; IMMUNOLOGY; IMMUNOTHERAPY; INFLAMMATION; INNATE IMMUNITY; INTESTINE MUCOSA; MICROBIOLOGY; NEOPLASM; PROCEDURES; WOUND HEALING;

ANTINEOPLASTIC AGENT;

ADAPTIVE IMMUNITY; ANIMALS; ANTINEOPLASTIC AGENTS; CARCINOGENESIS; HUMANS; IMMUNITY, INNATE; IMMUNOTHERAPY; INFLAMMATION; INTESTINAL MUCOSA; MICROBIOTA; NEOPLASMS; WOUND HEALING;

EID: 85018335347     PISSN: 07320582     EISSN: 15453278     Source Type: Book Series    
DOI: 10.1146/annurev-immunol-051116-052133     Document Type: Review

References (221)

1. Ley RE, Lozupone CA, Hamady M, Knight R, Gordon JI. 2008. Worlds within worlds: Evolution of the vertebrate gut microbiota. Nat. Rev. Microbiol. 6:776-88
2. Yutin N, Wolf MY, Wolf YI, Koonin EV. 2009. The origins of phagocytosis and eukaryogenesis. Biol. Direct 4:9
3. McInerney JO, O'Connell MJ, Pisani D. 2014. The hybrid nature of the Eukaryota and a consilient view of life on Earth. Nat. Rev. Microbiol. 12:449-55
4. Chovatiya R, Medzhitov R. 2014. Stress, inflammation, and defense of homeostasis. Mol. Cell 54:281-88
5. Chu H, Mazmanian SK. 2013. Innate immune recognition of the microbiota promotes host-microbial symbiosis. Nat. Immunol. 14:668-75
6. Hum. Microbiome Proj. Consort. 2012. Structure, function and diversity of the healthy human microbiome. Nature 486:207-14
7. Sender R, Fuchs S, Milo R. 2016. Are we really vastly outnumbered? revisiting the ratio of bacterial to host cells in humans. Cell 164:337-40
8. Bianconi E, Piovesan A, Facchin F, Beraudi A, Casadei R, et al. 2013. An estimation of the number of cells in the human body. Ann. Hum. Biol. 40:463-71
9. Bosch TC, McFall-Ngai MJ. 2011. Metaorganisms as the new frontier. Zoology 114:185-90
10. Costello EK, Stagaman K, Dethlefsen L, Bohannan BJ, Relman DA. 2012. The application of ecological theory toward an understanding of the human microbiome. Science 336:1255-62
11. McFall-Ngai M. 2008. Are biologists in 'future shock'? Symbiosis integrates biology across domains. Nat. Rev. Microbiol. 6:789-92
12. Candela M, Biagi E, Maccaferri S, Turroni S, Brigidi P. 2012. Intestinal microbiota is a plastic factor responding to environmental changes. Trends Microbiol. 20:385-91
13. Zeng MY, Cisalpino D, Varadarajan S, Hellman J, Warren HS, et al. 2016. Gut microbiota-induced immunoglobulinGcontrols systemic infection by symbiotic bacteria and pathogens. Immunity 44:647-58
14. Hand TW, Dos Santos LM, Bouladoux N, Molloy MJ, Pagan AJ, et al. 2012. Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses. Science 337:1553-56
15. Stewart EJ. 2012. Growing unculturable bacteria. J. Bacteriol. 194:4151-60
16. Goodman AL, Kallstrom G, Faith JJ, Reyes A, Moore A, et al. 2011. Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice. PNAS 108:6252-57
17. Tringe SG, Hugenholtz P. 2008. A renaissance for the pioneering 16S rRNA gene. Curr. Opin.Microbiol. 11:442-46
18. Schoch CL, Seifert KA, Huhndorf S, Robert V, Spouge JL, et al. 2012. Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi. PNAS 109:6241-46
19. Parfrey LW, Walters WA, Lauber CL, Clemente JC, Berg-Lyons D, et al. 2014. Communities of microbial eukaryotes in the mammalian gut within the context of environmental eukaryotic diversity. Front. Microbiol. 5:298
20. Morgun A, Dzutsev A, Dong X, Greer RL, Sexton DJ, et al. 2015. Uncovering effects of antibiotics on the host and microbiota using transkingdom gene networks. Gut 64:1732-43
21. Zeevi D, Korem T, Zmora N, Israeli D, Rothschild D, et al. 2015. Personalized nutrition by prediction of glycemic responses. Cell 163:1079-94
22. Belkaid Y, Hand TW. 2014. Role of the microbiota in immunity and inflammation. Cell 157:121-41
23. Cryan JF, Dinan TG. 2012. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat. Rev. Neurosci. 13:701-12
24. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, et al. 2010. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464:59-65
25. Tsai YC, Conlan S, Deming C, Segre JA, Kong HH, et al. 2016. Resolving the complexity of human skin metagenomes using single-molecule sequencing. mBio 7:e01948-15
26. Blekhman R, Goodrich JK, Huang K, Sun Q, Bukowski R, et al. 2015. Host genetic variation impacts microbiome composition across human body sites. Genome Biol. 16:191
27. Mueller NT, Bakacs E, Combellick J, Grigoryan Z, Dominguez-Bello MG.2015. The infantmicrobiome development: Mom matters. Trends Mol. Med. 21:109-17
28. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, et al. 2012. Human gut microbiome viewed across age and geography. Nature 486:222-27
29. Jackson MA, Jeffery IB, Beaumont M, Bell JT, Clark AG, et al. 2016. Signatures of early frailty in the gut microbiota. Genome Med. 8:8
30. O'Toole PW, Jeffery IB. 2015. Gut microbiota and aging. Science 350:1214-15
31. Brestoff JR, Artis D. 2013. Commensal bacteria at the interface of host metabolism and the immune system. Nat. Immunol. 14:676-84
32. Belkaid Y, Naik S. 2013. Compartmentalized and systemic control of tissue immunity by commensals. Nat. Immunol. 14:646-53
33. Ichinohe T, Pang IK, Kumamoto Y, Peaper DR, Ho JH, et al. 2011. Microbiota regulates immune defense against respiratory tract influenza A virus infection. PNAS 108:5354-59
34. Ganal SC, Sanos SL, Kallfass C, Oberle K, Johner C, et al. 2012. Priming of natural killer cells by nonmucosal mononuclear phagocytes requires instructive signals from commensal microbiota. Immunity 37:171-86
35. Abt MC. 2016. Acute gastroenteritis leaves a lasting impression. Cell Host Microbe 19:3-5
36. Chervonsky AV. 2013. Microbiota and autoimmunity. Cold Spring Harb. Perspect. Biol. 5:a007294
37. Naik S, Bouladoux N, Wilhelm C, Molloy MJ, Salcedo R, et al. 2012. Compartmentalized control of skin immunity by resident commensals. Science 337:1115-19
38. Vaishnava S, Behrendt CL, Ismail AS, Eckmann L, Hooper LV. 2008. Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface. PNAS 105:20858
39. Shen W, Li W, Hixon JA, Bouladoux N, Belkaid Y, et al. 2014. Adaptive immunity to murine skin commensals. PNAS 111:E2977-86
40. Khosravi A, Yanez A, Price JG, Chow A, Merad M, et al. 2014. Gut microbiota promote hematopoiesis to control bacterial infection. Cell Host Microbe. 15:374-81
41. Balmer ML, Schurch CM, Saito Y, Geuking MB, Li H, et al. 2014. Microbiota-derived compounds drive steady-state granulopoiesis via MyD88/TICAM signaling. J. Immunol. 193:5273-83
42. Trompette A, Gollwitzer ES, Yadava K, Sichelstiel AK, Sprenger N, et al. 2014. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat. Med. 20:159-66
43. Erny D, Hrabe de Angelis AL, Jaitin D, Wieghofer P, Staszewski O, et al. 2015. Host microbiota constantly control maturation and function of microglia in the CNS. Nat. Neurosci. 18:965-77
44. Zhang D, Chen G, Manwani D, Mortha A, Xu C, et al. 2015. Neutrophil ageing is regulated by the microbiome. Nature 525:528-32
45. Mukherji A, Kobiita A, Ye T, Chambon P. 2013. Homeostasis in intestinal epithelium is orchestrated by the circadian clock and microbiota cues transduced by TLRs. Cell 153:812-27
46. Nguyen KD, Fentress SJ, Qiu Y, Yun K, Cox JS, Chawla A. 2013. Circadian gene Bmal1 regulates diurnal oscillations of Ly6Chi inflammatory monocytes. Science 341:1483-88
47. Thaiss CA, Zeevi D, Levy M, Zilberman-Schapira G, Suez J, et al. 2014. Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell 159:514-29
48. Perussia B, Dayton ET, Fanning V, Thiagarajan P, Hoxie J, Trinchieri G. 1983. Immune interferon and leukocyte-conditioned medium induce normal and leukemic myeloid cells to differentiate along the monocytic pathway. J. Exp. Med. 158:2058-80
49. Colotta F, Re F, Polentarutti N, Sozzani S, Mantovani A. 1992. Modulation of granulocyte survival and programmed cell death by cytokines and bacterial products. Blood 80:2012-20
50. de Oliveira S, Rosowski EE, Huttenlocher A. 2016. Neutrophil migration in infection and wound repair: going forward in reverse. Nat. Rev. Immunol. 16:378-91
51. Askenase MH, Han S-J, Byrd AL, Morais da Fonseca D, Bouladoux N, et al. 2015. Bone-marrow-resident NK cells prime monocytes for regulatory function during infection. Immunity 42:1130-42
52. Gottschalk RA, Martins AJ, Angermann BR, Dutta B, Ng CE, et al. 2016. Distinct NF-κB andMAPK activation thresholds uncouple steady-statemicrobe sensing from anti-pathogen inflammatory responses. Cell Syst. 2:378-90
53. Iida N, Dzutsev A, Stewart CA, Smith L, Bouladoux N, et al. 2013. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 342:967-70
54. Ozmen L, Pericin M, Hakimi J, Chizzonite RA, Wysocka M, et al. 1994. Interleukin 12, interferon γ, and tumor necrosis factor aare the key cytokines of the generalized Shwartzman reaction. J. Exp. Med. 180:907-15
55. Hanahan D, Weinberg RA. 2000. The hallmarks of cancer. Cell 100:57-70
56. Fidler IJ. 2003. The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat. Rev. Cancer 3:453-58
57. Dolberg DS, Bissell MJ. 1984. Inability of Rous sarcoma virus to cause sarcomas in the avian embryo. Nature 309:552-56
58. Martincorena I, Roshan A, Gerstung M, Ellis P, Van Loo P, et al. 2015. Tumor evolution: high burden and pervasive positive selection of somatic mutations in normal human skin. Science 348:880-86
59. Bissell MJ, Hines WC. 2011. Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat. Med. 17:320-29
60. Adami J, Gabel H, Lindelof B, Ekstrom K, Rydh B, et al. 2003. Cancer risk following organ transplantation: a nationwide cohort study in Sweden. Br. J. Cancer 89:1221-27
61. Vogtmann E, Goedert JJ. 2016. Epidemiologic studies of the human microbiome and cancer. Br. J. Cancer 114:237-42
62. IARCWork. Group Evaluation Carcinog. Risks Hum. 1994. Schistosomes, Liver Flukes and Helicobacter pylori. IARCMonogr. Evaluation Carcinog. Risks Hum. Vol. 61. Geneva, Switz.: WorldHealthOrgan.
63. Atherton JC, Blaser MJ. 2009. Coadaptation of Helicobacter pylori and humans: ancient history, modern implications. J. Clin. Investig. 119:2475-87
64. Kostic AD, Chun E, Robertson L, Glickman JN, Gallini CA, et al. 2013. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 14:207-15
65. Sears CL, Garrett WS. 2014. Microbes, microbiota, and colon cancer. Cell Host Microbe 15:317-28
66. Morgan XC, Tickle TL, Sokol H, Gevers D, Devaney KL, et al. 2012. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol. 13:R79
67. Arthur JC, Perez-Chanona E, Muhlbauer M, Tomkovich S, Uronis JM, et al. 2012. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 338:120-23
68. Thomas RM, Jobin C. 2015. The microbiome and cancer: Is the 'oncobiome' mirage real? Trends Cancer 1:24-35
69. Poutahidis T, Varian BJ, Levkovich T, Lakritz JR, Mirabal S, et al. 2015. Dietary microbes modulate transgenerational cancer risk. Cancer Res. 75:1197-204
70. Bhaskaran K, Douglas I, Forbes H, dos-Santos-Silva I, Leon DA, Smeeth L. 2014. Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5.24 million UK adults. Lancet 384:755-65
71. Conroy MJ, Dunne MR, Donohoe CL, Reynolds JV. 2016. Obesity-associated cancer: an immunological perspective. Proc. Nutr. Soc. 75:125-38
72. Beyaz S, Mana MD, Roper J, Kedrin D, Saadatpour A, et al. 2016. High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature 531:53-58
73. Ohtani N, Yoshimoto S, Hara E. 2014. Obesity and cancer: a gut microbial connection. Cancer Res. 74:1885-89
74. Abnet CC, Corley DA, Freedman ND, Kamangar F. 2015. Diet and upper gastrointestinalmalignancies. Gastroenterology 148:1234-43.e4
75. Doll R, Peto R. 1981. The causes of cancer: Quantitative estimates of avoidable risks of cancer in the United States today. J. Natl. Cancer Inst. 66:1191-308
76. Song M, Garrett WS, Chan AT. 2015. Nutrients, foods, and colorectal cancer prevention. Gastroenterology 148:1244-60.e16
77. Wei W, Sun W, Yu S, Yang Y, Ai L. 2016. Butyrate production from high-fiber diet protects against lymphoma tumor. Leuk. Lymphoma 57:2401-8
78. Masuyama H, Mitsui T, Nobumoto E, Hiramatsu Y. 2015. The effects of high-fat diet exposure in utero on the obesogenic and diabetogenic traits through epigenetic changes in adiponectin and leptin gene expression for multiple generations in female mice. Endocrinology 156:2482-91
79. Modi SR, Collins JJ, Relman DA. 2014. Antibiotics and the gutmicrobiota. J. Clin. Investig. 124:4212-18
80. Cho I, Yamanishi S, Cox L, Methe BA, Zavadil J, et al. 2012. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature 488:621-26
81. Scott FI, Horton DB, Mamtani R, Haynes K, Goldberg DS, et al. 2016. Administration of antibiotics to children before age 2 years increases risk for childhood obesity. Gastroenterology 151:120-129.e5
82. Hviid A, Svanstrom H, Frisch M. 2011. Antibiotic use and inflammatory bowel diseases in childhood. Gut 60:49-54
83. Sergentanis TN, Zagouri F, Zografos GC. 2010. Is antibiotic use a risk factor for breast cancer? A meta-analysis. Pharmacoepidemiol. Drug Saf. 19:1101-7
84. Xuan C, Shamonki JM, Chung A, Dinome ML, Chung M, et al. 2014. Microbial dysbiosis is associated with human breast cancer. PLOS ONE 9:e83744
85. Lee YY, Mahendra Raj S, Graham DY. 2013. Helicobacter pylori infection-a boon or a bane: lessons from studies in a low-prevalence population. Helicobacter 18:338-46
86. Levkovich T, Poutahidis T, Cappelle K, Smith MB, Perrotta A, et al. 2014. 'Hygienic' lymphocytes convey increased cancer risk. J. Anal. Oncol. 3:113-21
87. Fonseca DM, Hand TW, Han S-J, Gerner MY, Glatman Zaretsky A, et al. 2015. Microbiota-dependent sequelae of acute infection compromise tissue-specific immunity. Cell 163:354-66
88. Chen JA, Splenser A, Guillory B, Luo J, Mendiratta M, et al. 2015. Ghrelin prevents tumour-and cisplatin-induced muscle wasting: characterization of multiple mechanisms involved. J. Cachexia Sarcopenia Muscle 6:132-43
89. de Matos-Neto EM, Lima JDCC, de Pereira WO, Figueredo RG, Riccardi DMDR, et al. 2015. Systemic inflammation in cachexia-is tumor cytokine expression profile the culprit? Front. Immunol. 6:629
90. Kir S, White JP, Kleiner S, Kazak L, Cohen P, et al. 2014. Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia. Nature 513:100-4
91. Armougom F, Henry M, Vialettes B, Raccah D, Raoult D. 2009. Monitoring bacterial community of human gut microbiota reveals an increase in Lactobacillus in obese patients and Methanogens in anorexic patients. PLOS ONE 4:e7125
92. Varian BJ, Goureshetti S, Poutahidis T, Lakritz JR, Levkovich T, et al. 2016. Beneficial bacteria inhibit cachexia. Oncotarget 7:11803-16
93. Bindels LB, Neyrinck AM, Claus SP, Le Roy CI, Grangette C, et al. 2016. Synbiotic approach restores intestinal homeostasis and prolongs survival in leukaemic mice with cachexia. ISME J. 10:1456-70
94. Schieber AMP, Lee YM, Chang MW, Leblanc M, Collins B, et al. 2015. Disease tolerance mediated by microbiome E. coli involves inflammasome and IGF-1 signaling. Science 350:558-63
95. Klein GL, Petschow BW, Shaw AL, Weaver E. 2013. Gut barrier dysfunction and microbial translocation in cancer cachexia: a new therapeutic target. Curr. Opin. Support. Palliat. Care 7:361-67
96. de Martel C, Ferlay J, Franceschi S, Vignat J, Bray F, et al. 2012. Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol. 13:607-15
97. IARC Work. Group Evaluation Carcinog. Risks Hum. 2012. A Review of Human Carcinogens: Part B; Biological agents. IARC Monogr. Evaluation Carcinog. Risks Hum. Vol. 100B. Geneva, Switz.: World Health Organ.
98. Zhang X, Zhang Z, Zheng B, He Z, Winberg G, Ernberg I. 2013. An update on viral association of human cancers. Arch. Virol. 158:1433-43
99. Ng J, Wu J. 2012. Hepatitis B-and hepatitis C-related hepatocellular carcinomas in the United States: similarities and differences. Hepat. Mon. 12:e7635
100. Psyrri A, Rampias T, Vermorken JB. 2014. The current and future impact of human papillomavirus on treatment of squamous cell carcinoma of the head and neck. Ann. Oncol. 25:2101-15
101. Tommasino M. 2014. The human papillomavirus family and its role in carcinogenesis. Semin. Cancer Biol. 26:13-21
102. Ciminale V, Rende F, Bertazzoni U, Romanelli MG.2014. HTLV-1 andHTLV-2: highly similar viruses with distinct oncogenic properties. Front. Microbiol. 5:398
103. Feng H, Shuda M, Chang Y, Moore PS. 2008. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 319:1096-100
104. Zheng ZM. 2010. Viral oncogenes, noncoding RNAs, and RNA splicing in human tumor viruses. Int. J. Biol. Sci. 6:730-55
105. Mitra A, MacIntyre DA, Lee YS, Smith A, Marchesi JR, et al. 2015. Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity. Sci. Rep. 5:16865
106. Rehermann B, Nascimbeni M. 2005. Immunology of hepatitis B virus and hepatitis C virus infection. Nature Rev. Immunol. 5:215-29
107. Bender S, Reuter A, Eberle F, Einhorn E, Binder M, Bartenschlager R. 2015. Activation of type I and III interferon response by mitochondrial and peroxisomal MAVS and inhibition by hepatitis C virus. PLOS Pathog. 11:e1005264
108. Chen Y, Chen Z, Guo R, Chen N, Lu H, et al. 2011. Correlation between gastrointestinal fungi and varying degrees of chronic hepatitis B virus infection. Diagn. Microbiol. Infect. Dis. 70:492-98
109. Xu M, Wang B, Fu Y, Chen Y, Yang F, et al. 2012. Changes of fecal Bifidobacterium species in adult patients with hepatitis B virus-induced chronic liver disease. Microb. Ecol. 63:304-13
110. Henao-Mejia J, Elinav E, Thaiss CA, Licona-Limon P, Flavell RA. 2013. Role of the intestinal microbiome in liver disease. J. Autoimmun. 46:66-73
111. Chou HH, Chien WH, Wu LL, Cheng CH, Chung CH, et al. 2015. Age-related immune clearance of hepatitis B virus infection requires the establishment of gut microbiota. PNAS 112:2175-80
112. Moore PS, Chang Y. 2010. Why do viruses cause cancer? Highlights of the first century of human tumour virology. Nat. Rev. Cancer 10:878-89
113. Ki MR, Hwang M, Kim AY, Lee EM, Lee EJ, et al. 2014. Role of vacuolating cytotoxin VacA and cytotoxin-associated antigen CagA of Helicobacter pylori in the progression of gastric cancer. Mol. Cell Biochem. 396:23-32
114. Khosravi Y, Bunte RM, Chiow KH, Tan TL, Wong WY, et al. 2016. Helicobacter pylori and gut microbiota modulate energy homeostasis prior to inducing histopathological changes in mice. Gut Microbes 7:48-53
115. Perry S, de Jong BC, Solnick JV, de la Luz Sanchez M, Yang S, et al. 2010. Infection with Helicobacter pylori is associated with protection against tuberculosis. PLOS ONE 5:e8804
116. Koch KN, Hartung ML, Urban S, Kyburz A, Bahlmann AS, et al. 2015. Helicobacter urease-induced activation of the TLR2/NLRP3/IL-18 axis protects against asthma. J. Clin. Investig. 125:3297-302
117. Kim DJ, Park JH, Franchi L, Backert S, Nunez G. 2013. The Cag pathogenicity island and interaction between TLR2/NOD2 and NLRP3 regulate IL-1βproduction in Helicobacter pylori infected dendritic cells. Eur. J. Immunol. 43:2650-58
118. Peek RM Jr., Blaser MJ. 2002. Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat. Rev. Cancer 2:28-37
119. Plottel CS, Blaser MJ. 2011. Microbiome and malignancy. Cell Host Microbe 10:324-35
120. Yap TW, Gan HM, Lee YP, Leow AH, Azmi AN, et al. 2016. Helicobacter pylori eradication causes perturbation of the human gut microbiome in young adults. PLOS ONE 11:e0151893
121. Belkaid Y, Segre JA. 2014. Dialogue between skin microbiota and immunity. Science 346:954-59
122. Goldszmid RS, Trinchieri G. 2012. The price of immunity. Nat. Immunol. 13:932-38
123. Jobin C. 2012. Colorectal cancer: CRC-all about microbial products and barrier function? Nat. Rev. Gastroenterol. Hepatol. 9:694-96
124. Rao VP, Poutahidis T, Ge Z, Nambiar PR, Boussahmain C, et al. 2006. Innate immune inflammatory response against enteric bacteria Helicobacter hepaticus induces mammary adenocarcinoma inmice. Cancer Res. 66:7395-400
125. Attene-Ramos MS, Wagner ED, Plewa MJ, Gaskins HR. 2006. Evidence that hydrogen sulfide is a genotoxic agent. Mol. Cancer Res. 4:9-14
126. Andriamihaja M, Lan A, Beaumont M, Audebert M, Wong X, et al. 2015. The deleterious metabolic and genotoxic effects of the bacterial metabolite p-cresol on colonic epithelial cells. Free Radic. Biol.Med. 85:219-27
127. Garrett WS, Lord GM, Punit S, Lugo-Villarino G, Mazmanian SK. 2007. Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell 131:33
128. Elinav E, Strowig T, Kau AL, Henao-Mejia J, Thaiss CA, et al. 2011. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 145:745-57
129. Rubinstein MR, Wang X, Liu W, Hao Y, Cai G, Han YW. 2013. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin. Cell Host Microbe 14:195-206
130. Zackular JP, Baxter NT, Iverson KD, Sadler WD, Petrosino JF, et al. 2013. The gut microbiome modulates colon tumorigenesis. mBio 4:e00692-13
131. Mira-Pascual L, Cabrera-Rubio R, Ocon S, Costales P, Parra A, et al. 2015. Microbial mucosal colonic shifts associated with the development of colorectal cancer reveal the presence of different bacterial and archaeal biomarkers. J. Gastroenterol. 50:167-79
132. Okuda T, Kokubu E, Kawana T, Saito A, Okuda K, Ishihara K. 2012. Synergy in biofilm formation between Fusobacterium nucleatum and Prevotella species. Anaerobe 18:110-16
133. Abed J, Emgard JE, Zamir G, Faroja M, Almogy G, et al. 2016. Fap2 mediates Fusobacterium nucleatum colorectal adenocarcinoma enrichment by binding to tumor-expressed Gal-GalNAc. Cell Host Microbe 20:215-25
134. Gur C, Ibrahim Y, Isaacson B, Yamin R, Abed J, et al. 2015. Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. Immunity 42:344-55
135. Dejea CM, Wick EC, Hechenbleikner EM, White JR, Mark Welch JL, et al. 2014. Microbiota organization is a distinct feature of proximal colorectal cancers. PNAS 111:18321-26
136. Johnson CH, Dejea CM, Edler D, Hoang LT, Santidrian AF, et al. 2015. Metabolism links bacterial biofilms and colon carcinogenesis. Cell Metab. 21:891-97
137. Dalmasso G, Cougnoux A, Delmas J, Darfeuille-Michaud A, Bonnet R. 2014. The bacterial genotoxin colibactin promotes colon tumor growth by modifying the tumormicroenvironment. Gut Microbes 5:675-80
138. Nesic D, Hsu Y, Stebbins CE. 2004. Assembly and function of a bacterial genotoxin. Nature 429:429-33
139. Kim JJ, Tao H, Carloni E, Leung WK, Graham DY, Sepulveda AR. 2002. Helicobacter pylori impairs DNA mismatch repair in gastric epithelial cells. Gastroenterology 123:542-53
140. Maddocks OD, Short AJ, Donnenberg MS, Bader S, Harrison DJ. 2009. Attaching and effacing Escherichia coli downregulate DNA mismatch repair protein in vitro and are associated with colorectal adenocarcinomas in humans. PLOS ONE 4:e5517
141. Yao Q, Zhang L, Wan X, Chen J, Hu L, et al. 2014. Structure and specificity of the bacterial cysteine methyltransferase effectorNleE suggests a novel substrate in human DNA repair pathway. PLOS Pathog. 10:e1004522
142. Boleij A, Hechenbleikner EM, Goodwin AC, Badani R, Stein EM, et al. 2015. The Bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients. Clin. Infect. Dis. 60:208-15
143. Wick EC, Rabizadeh S, Albesiano E, Wu X, Wu S, et al. 2014. Stat3 activation in murine colitis induced by enterotoxigenic Bacteroides fragilis. Inflamm. Bowel Dis. 20:821-34
144. Geis AL, Fan H, Wu X, Wu S, Huso DL, et al. 2015. Regulatory T-cell response to enterotoxigenic Bacteroides fragilis colonization triggers IL17-dependent colon carcinogenesis. Cancer Discov. 5:1098-109
145. Grivennikov SI, Wang K, Mucida D, Stewart CA, Schnabl B, et al. 2012. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 491:254-58
146. Ernst M, Putoczki TL. 2013. Targeting IL-11 signaling in colon cancer. Oncotarget 4:1860-61
147. Salcedo R, Worschech A, Cardone M, Jones Y, Gyulai Z, et al. 2010. MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18. J. Exp. Med. 207:1625-36
148. Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, et al. 2012. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482:179-85
149. Macia L, Tan J, Vieira AT, Leach K, Stanley D, et al. 2015. Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. Nat. Commun. 6:6734
150. Chudnovskiy A, Mortha A, Kana V, Kennard A, Ramirez JD, et al. 2016. Host-protozoan interactions protect from mucosal infections through activation of the inflammasome. Cell 167:444-56
151. Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, et al. 2013. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341:569-73
152. Singh N, Gurav A, Sivaprakasam S, Brady E, Padia R, et al. 2014. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 40:128-39
153. Saleh M, Trinchieri G. 2011. Innate immune mechanisms of colitis and colitis-associated colorectal cancer. Nat. Rev. Immunol. 11:9-20
154. Huber S, Gagliani N, Zenewicz LA, Huber FJ, Bosurgi L, et al. 2012. IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine. Nature 491:259-63
155. Kirchberger S, Royston DJ, Boulard O, Thornton E, Franchini F, et al. 2013. Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model. J. Exp. Med. 210:917-31
156. Munoz M, Eidenschenk C, Ota N, Wong K, Lohmann U, et al. 2015. Interleukin-22 induces interleukin-18 expression from epithelial cells during intestinal infection. Immunity 42:321-31
157. Nowarski R, Jackson R, Gagliani N, de Zoete MR, Palm NW, et al. 2015. Epithelial IL-18 equilibrium controls barrier function in colitis. Cell 163:1444-56
158. Elangovan S, Pathania R, Ramachandran S, Ananth S, Padia RN, et al. 2014. The niacin/butyrate receptor GPR109A suppresses mammary tumorigenesis by inhibiting cell survival. Cancer Res. 74:1166-78
159. Van den Abbeele P, Belzer C, Goossens M, Kleerebezem M, De Vos WM, et al. 2013. Butyrate-producing Clostridium cluster XIVa species specifically colonize mucins in an in vitro gut model. ISME J. 7:949-61
160. Tan J, McKenzie C, Potamitis M, Thorburn AN, Mackay CR, Macia L. 2014. The role of short-chain fatty acids in health and disease. Adv. Immunol. 121:91-119
161. Belcheva A, Irrazabal T, Robertson SJ, Streutker C, Maughan H, et al. 2014. Gut microbial metabolism drives transformation of Msh2-deficient colon epithelial cells. Cell 158:288-99
162. Uittamo J, Siikala E, Kaihovaara P, Salaspuro M, Rautemaa R. 2009. Chronic candidosis and oral cancer in APECED-patients: production of carcinogenic acetaldehyde from glucose and ethanol by Candida albicans. Int. J. Cancer 124:754-56
163. Howitt MR, Lavoie S, Michaud M, Blum AM, Tran SV, et al. 2016. Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut. Science 351:1329-33
164. Nowak A, Czyzowska A, Huben K, Sojka M, Kuberski S, et al. 2016. Prebiotics and age, but not probiotics affect the transformation of 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ) by fecal microbiota-an in vitro study. Anaerobe 39:124-35
165. Megaraj V, Ding X, Fang C, Kovalchuk N, Zhu Y, Zhang QY. 2014. Role of hepatic and intestinal p450 enzymes in the metabolic activation of the colon carcinogen azoxymethane in mice. Chem. Res. Toxicol. 27:656-62
166. Morita N, Walaszek Z, Kinjo T, Nishimaki T, Hanausek M, et al. 2008. Effects of synthetic and natural in vivo inhibitors of β-glucuronidase on azoxymethane-induced colon carcinogenesis in rats. Mol. Med. Rep. 1:741-46
167. Vergara-Castaneda HA, Guevara-Gonzalez RG, Ramos-Gomez M, Reynoso-Camacho R, Guzman-Maldonado H, et al. 2010. Non-digestible fraction of cooked bean (Phaseolus vulgaris L.) cultivar Bayo Madero suppresses colonic aberrant crypt foci in azoxymethane-induced rats. Food Funct. 1:294-300
168. Kim YG, Udayanga KG, Totsuka N, Weinberg JB, Nunez G, Shibuya A. 2014. Gut dysbiosis promotes M2macrophage polarization and allergic airway inflammation via fungi-induced PGE2. Cell Host Microbe. 15:95-102
169. Nagamine CM, Sohn JJ, Rickman BH, Rogers AB, Fox JG, Schauer DB. 2008. Helicobacter hepaticus infection promotes colon tumorigenesis in the BALB/c-Rag2-/-ApcMin/+ mouse. Infect. Immun. 76:2758-66
170. Poutahidis T, Cappelle K, Levkovich T, Lee CW, Doulberis M, et al. 2013. Pathogenic intestinal bacteria enhance prostate cancer development via systemic activation of immune cells in mice. PLOS ONE 8:e73933
171. Fox JG, Feng Y, Theve EJ, Raczynski AR, Fiala JL, et al. 2010. Gut microbes define liver cancer risk in mice exposed to chemical and viral transgenic hepatocarcinogens. Gut 59:88-97
172. Erdman SE, Poutahidis T, Tomczak M, Rogers AB, Cormier K, et al. 2003. CD4+ CD25+ regulatory T lymphocytes inhibitmicrobially induced colon cancer inRag2-deficient mice.Am. J. Pathol. 162:691-702
173. Lakritz JR, Poutahidis T, Mirabal S, Varian BJ, Levkovich T, et al. 2015. Gut bacteria require neutrophils to promote mammary tumorigenesis. Oncotarget 6:9387-96
174. Yamamoto ML, Maier I, Dang AT, Berry D, Liu J, et al. 2013. Intestinal bacteria modify lymphoma incidence and latency by affecting systemic inflammatory state, oxidative stress, and leukocyte genotoxicity. Cancer Res. 73:4222-32
175. Westbrook AM, Wei B, Hacke K, Xia M, Braun J, Schiestl RH. 2012. The role of tumour necrosis factor-aand tumour necrosis factor receptor signalling in inflammation-associated systemic genotoxicity. Mutagenesis 27:77-86
176. Rutkowski MR, Stephen TL, Svoronos N, Allegrezza MJ, Tesone AJ, et al. 2015. Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation. Cancer Cell 27:27-40
177. ColeyWB. 1893. Treatment of malignant tumors by repeated inoculation of erysipelas: with a report of 10 cases. Am. J. Med. Sci. 105:487-564
178. Tang DH, Chang SS. 2015. Management of carcinoma in situ of the bladder: best practice and recent developments. Adv. Urol. 7:351-64
179. Forbes NS. 2010. Engineering the perfect (bacterial) cancer therapy. Nat. Rev. Cancer 10:785-94
180. Bettegowda C, Huang X, Lin J, Cheong I, Kohli M, et al. 2006. The genome and transcriptomes of the anti-tumor agent Clostridium novyi-NT. Nat. Biotechnol. 24:1573-80
181. Forbes NS. 2006. Profile of a bacterial tumor killer. Nat. Biotechnol. 24:1484-85
182. Mlynarczyk GS, Berg CA, Withrock IC, Fick ME, Anderson SJ, et al. 2014. Salmonella as a biological "Trojan horse" for neoplasia: future possibilities including brain cancer. Med. Hypotheses 83:343-45
183. Zhang M, Forbes NS. 2015. Trg-deficient Salmonella colonize quiescent tumor regions by exclusively penetrating or proliferating. J. Control Release 199:180-89
184. Spanogiannopoulos P, Bess EN, Carmody RN, Turnbaugh PJ. 2016. The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism. Nat. Rev. Microbiol. 14:273-87
185. Dzutsev A, Goldszmid RS, Viaud S, Zitvogel L, Trinchieri G. 2015. The role of the microbiota in inflammation, carcinogenesis, and cancer therapy. Eur. J. Immunol. 45:17-31
186. Li H, Jia W. 2013. Cometabolism of microbes and host: implications for drug metabolism and druginduced toxicity. Clin. Pharmacol. Ther. 94:574-81
187. Maurice CF, Haiser HJ, Turnbaugh PJ. 2013. Xenobiotics shape the physiology and gene expression of the active human gut microbiome. Cell 152:39-50
188. Fujita K, Sparreboom A. 2010. Pharmacogenetics of irinotecan disposition and toxicity: a review. Curr. Clin. Pharmacol. 5:209-17
189. Stringer AM, Gibson RJ, Logan RM, Bowen JM, Yeoh AS, Keefe DM. 2008. Faecal microflora and β-glucuronidase expression are altered in an irinotecan-induced diarrhea model in rats. Cancer Biol. Ther. 7:1919-25
190. McIntosh FM, Maison N, Holtrop G, Young P, Stevens VJ, et al. 2012. Phylogenetic distribution of genes encoding β-glucuronidase activity in human colonic bacteria and the impact of diet on faecal glycosidase activities. Environ. Microbiol. 14:1876-87
191. Wallace BD, Wang H, Lane KT, Scott JE, Orans J, et al. 2010. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science 330:831-35
192. Galluzzi L, Vitale I, Michels J, Brenner C, Szabadkai G, et al. 2014. Systems biology of cisplatin resistance: past, present and future. Cell Death Dis. 5:e1257
193. Roy S, Ryals MM, Van den Bruele AB, Fitzgerald TS, Cunningham LL. 2013. Sound preconditioning therapy inhibits ototoxic hearing loss in mice. J. Clin. Investig. 123:4945-49
194. Zhu S, Pabla N, Tang C, He L, Dong Z. 2015. DNA damage response in cisplatin-induced nephrotoxicity. Arch. Toxicol. 89:2197-205
195. Park SB, Goldstein D, Krishnan AV, Lin CSY, Friedlander ML, et al. 2013. Chemotherapy-induced peripheral neurotoxicity: a critical analysis. CA Cancer J. Clin. 63:419-37
196. Laurent A, Nicco C, Chereau C, Goulvestre C, Alexandre J, et al. 2005. Controlling tumor growth by modulating endogenous production of reactive oxygen species. Cancer Res. 65:948-56
197. Gui QF, Lu HF, Zhang CX, Xu ZR, Yang YH. 2015. Well-balanced commensal microbiota contributes to anti-cancer response in a lung cancer mouse model. Genet. Mol. Res. 14:5642-51
198. Chitapanarux I, Chitapanarux T, Traisathit P, Kudumpee S, Tharavichitkul E, Lorvidhaya V. 2010. Randomized controlled trial of live Lactobacillus acidophilus plus Bifidobacterium bifidum in prophylaxis of diarrhea during radiotherapy in cervical cancer patients. Radiat. Oncol. 5:31
199. Wang Y, Luo X, Pan H, Huang W, Wang X, et al. 2015. Pharmacological inhibition of NADPH oxidase protects against cisplatin induced nephrotoxicity in mice by two step mechanism. Food Chem. Toxicol. 83:251-60
200. Dhiman RK. 2013. Gut microbiota and hepatic encephalopathy. Metab. Brain Dis. 28:321-26
201. Viaud S, Saccheri F, Mignot G, Yamazaki T, Daillere R, et al. 2013. The intestinalmicrobiotamodulates the anticancer immune effects of cyclophosphamide. Science 342:971-6
202. Zwielehner J, Lassl C, Hippe B, Pointner A, Switzeny OJ, et al. 2011. Changes in human fecal microbiota due to chemotherapy analyzed byTaqMan-PCR, 454 sequencing andPCR-DGGEfingerprinting.PLOS ONE 6:e28654
203. Daillere R, Vetizou M, Waldschmitt N, Yamazaki T, Isnard C, et al. 2016. Enterococcus hirae and Barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects. Immunity 45:931-43
204. Couzin-Frankel J. 2013. Breakthrough of the year 2013: cancer immunotherapy. Science 342:1432-33
205. Vetizou M, Pitt JM, Daillere R, Lepage P, Waldschmitt N, et al. 2015. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350:1079-84
206. Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, et al. 2015. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350:1084-89
207. Paulos CM, Wrzesinski C, Kaiser A, Hinrichs CS, Chieppa M, et al. 2007. Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8+ T cells via TLR4 signaling. J. Clin. Investig. 117:2197-204
208. Guiducci C, Vicari AP, Sangaletti S, Trinchieri G, Colombo MP. 2005. Redirecting in vivo elicited tumor infiltrating macrophages and dendritic cells towards tumor rejection. Cancer Res. 65:3437-46
209. Vicari AP, Chiodoni C, Vaure C, Ait-Yahia S, Dercamp C, et al. 2002. Reversal of tumor-induced dendritic cell paralysis by CpG immunostimulatory oligonucleotide and anti-interleukin 10 receptor antibody. J. Exp. Med. 196:541-49
210. Stewart CA, Metheny H, Iida N, Smith L, Hanson M, et al. 2013. Interferon-dependent IL-10 production by Tregs limits tumor Th17 inflammation. J. Clin. Investig. 123:4859-74
211. Netea MG, Joosten LA, Latz E, Mills KH, Natoli G, et al. 2016. Trained immunity: a program of innate immune memory in health and disease. Science 352:aaf1098
212. Schreiber RD, Old LJ, Smyth MJ. 2011. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science 331:1565-70
213. Page DB, Postow MA, Callahan MK, Allison JP, Wolchok JD. 2014. Immune modulation in cancer with antibodies. Annu. Rev. Med. 65:185-202
214. Sharma P, Allison JP. 2015. The future of immune checkpoint therapy. Science 348:56-61
215. Teply BA, Lipson EJ. 2014. Identification and management of toxicities from immune checkpointblocking drugs. Oncology 28(Suppl. 3):30-38
216. Dubin K, Callahan MK, Ren B, Khanin R, Viale A, et al. 2016. Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis. Nat. Commun. 7:10391
217. Santiago-Rodriguez TM, Ly M, Daigneault MC, Brown IH, McDonald JA, et al. 2015. Chemostat culture systems support diverse bacteriophage communities from human feces. Microbiome 3:58
218. Kim HJ, Li H, Collins JJ, Ingber DE. 2016. Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip. PNAS 113:E7-15
219. Goldszmid RS, Dzutsev A, Viaud S, Zitvogel L, Restifo NP, Trinchieri G. 2015. Microbiotamodulation of myeloid cells in cancer therapy. Cancer Immunol. Res. 3:103-9
220. Kelly CR, Ihunnah C, Fischer M, Khoruts A, Surawicz C, et al. 2014. Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients. Am. J. Gastroenterol. 109:1065-71
221. Buffie CG, Bucci V, Stein RR, McKenney PT, Ling L, et al. 2015. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517:205-8