Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Molecular Cancer
Published in: Molecular Cancer 1/2019

Open Access 01-12-2019 | Hepatitis B | Review

The microbiota and microbiome in pancreatic cancer: more influential than expected

Authors: Miao-Yan Wei, Si Shi, Chen Liang, Qing-Cai Meng, Jie Hua, Yi-Yin Zhang, Jiang Liu, Bo Zhang, Jin Xu, Xian-Jun Yu

Published in: Molecular Cancer | Issue 1/2019

Login to get access

Abstract

Microbiota is just beginning to be recognized as an important player in carcinogenesis and the interplay among microbes is greater than expected. Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease for which mortality closely parallels incidence. Early detection would provide the best opportunity to increase survival rates. Specific well-studied oral, gastrointestinal, and intrapancreatic microbes and some kinds of hepatotropic viruses and bactibilia may have potential etiological roles in pancreatic carcinogenesis, or modulating individual responses to oncotherapy. Concrete mechanisms mainly involve perpetuating inflammation, regulating the immune system-microbe-tumor axis, affecting metabolism, and altering the tumor microenvironment. The revolutionary technology of omics has generated insight into cancer microbiomes. A better understanding of the microbiota in PDAC might lead to the establishment of screening or early-stage diagnosis methods, implementation of cancer bacteriotherapy, adjustment of therapeutic efficacy even alleviating the adverse effects, creating new opportunities and fostering hope for desperate PDAC patients.
Literature
1.
Human Microbiome Project C. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486:207–14.CrossRef
2.
Rajpoot M, Sharma AK, Sharma A, Gupta GK. Understanding the microbiome: Emerging biomarkers for exploiting the microbiota for personalized medicine against cancer. Semin Cancer Biol. 2018;52:1–8.PubMedCrossRef
3.
Staley C, Weingarden AR, Khoruts A, Sadowsky MJ. Interaction of gut microbiota with bile acid metabolism and its influence on disease states. Appl Microbiol Biotechnol. 2017;101:47–64.PubMedCrossRef
4.
Tilg H, Adolph TE. Beyond Digestion: The Pancreas Shapes Intestinal Microbiota and Immunity. Cell Metab. 2017;25:495–6.PubMedCrossRef
5.
de Martel C, Ferlay J, Franceschi S, Vignat J, Bray F, Forman D, Plummer M. Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol. 2012;13:607–15.PubMedCrossRef
6.
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. 2009;15:1016–22.PubMedPubMedCentralCrossRef
7.
Housseau F, Sears CL. Enterotoxigenic Bacteroides fragilis (ETBF)-mediated colitis in Min (Apc+/−) mice: a human commensal-based murine model of colon carcinogenesis. Cell Cycle. 2010;9:3–5.PubMedCrossRef
8.
9.
10.
Chung L, Thiele Orberg E, Geis AL, Chan JL, Fu K, DeStefano Shields CE, Dejea CM, Fathi P, Chen J, Finard BB, et al. Bacteroides fragilis Toxin Coordinates a Pro-carcinogenic Inflammatory Cascade via Targeting of Colonic Epithelial Cells. Cell Host Microbe. 2018;23:203–214 e205.PubMedPubMedCentralCrossRef
11.
Kwong TNY, Wang X, Nakatsu G, Chow TC, Tipoe T, Dai RZW, Tsoi KKK, Wong MCS, Tse G, Chan MTV, et al. Association Between Bacteremia From Specific Microbes and Subsequent Diagnosis of Colorectal Cancer. Gastroenterology. 2018;155:383–390 e388.PubMedCrossRef
12.
Li J, Sung CY, Lee N, Ni Y, Pihlajamaki J, Panagiotou G, El-Nezami H. Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice. Proc Natl Acad Sci U S A. 2016;113:E1306–15.PubMedPubMedCentralCrossRef
13.
Loo TM, Kamachi F, Watanabe Y, Yoshimoto S, Kanda H, Arai Y, Nakajima-Takagi Y, Iwama A, Koga T, Sugimoto Y, et al. Gut Microbiota Promotes Obesity-Associated Liver Cancer through PGE2-Mediated Suppression of Antitumor Immunity. Cancer Discov. 2017;7:522–38.PubMedCrossRef
14.
15.
Ma C, Han M, Heinrich B, Fu Q, Zhang Q, Sandhu M, Agdashian D, Terabe M, Berzofsky JA, Fako V, et al. Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells. Science. 2018;360(6391):eaan5931.PubMedCrossRefPubMedCentral
16.
Borrelli A, Bonelli P, Tuccillo FM, Goldfine ID, Evans JL, Buonaguro FM, Mancini A. Role of gut microbiota and oxidative stress in the progression of non-alcoholic fatty liver disease to hepatocarcinoma: Current and innovative therapeutic approaches. Redox Biol. 2018;15:467–79.PubMedPubMedCentralCrossRef
17.
18.
19.
Ertz-Archambault N, Keim P, Von Hoff D. Microbiome and pancreatic cancer: A comprehensive topic review of literature. World J Gastroenterol. 2017;23:1899–908.PubMedPubMedCentralCrossRef
20.
21.
22.
23.
Jotwani R, Cutler CW. Adult periodontitis--specific bacterial infection or chronic inflammation? J Med Microbiol. 1998;47:187–8.PubMedCrossRef
24.
Hujoel PP, Drangsholt M, Spiekerman C, Weiss NS. An exploration of the periodontitis-cancer association. Ann Epidemiol. 2003;13:312–6.PubMedCrossRef
25.
Michaud DS, Joshipura K, Giovannucci E, Fuchs CS. A prospective study of periodontal disease and pancreatic cancer in US male health professionals. J Natl Cancer Inst. 2007;99:171–5.PubMedCrossRef
26.
Michaud DS, Liu Y, Meyer M, Giovannucci E, Joshipura K. Periodontal disease, tooth loss, and cancer risk in male health professionals: a prospective cohort study. Lancet Oncol. 2008;9:550–8.PubMedPubMedCentralCrossRef
27.
Ahn J, Segers S, Hayes RB. Periodontal disease, Porphyromonas gingivalis serum antibody levels and orodigestive cancer mortality. Carcinogenesis. 2012;33:1055–8.PubMedPubMedCentralCrossRef
28.
Michaud DS, Izard J, Wilhelm-Benartzi CS, You DH, Grote VA, Tjonneland A, Dahm CC, Overvad K, Jenab M, Fedirko V, et al. Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study. Gut. 2013;62:1764–70.PubMedCrossRef
29.
Bracci PM. Oral Health and the Oral Microbiome in Pancreatic Cancer: An Overview of Epidemiological Studies. Cancer J. 2017;23:310–4.PubMedCrossRef
30.
Heikkila P, But A, Sorsa T, Haukka J. Periodontitis and cancer mortality: Register-based cohort study of 68,273 adults in 10-year follow-up. Int J Cancer. 2018;142:2244–53.PubMedCrossRef
31.
Tezal M, Sullivan MA, Hyland A, Marshall JR, Stoler D, Reid ME, Loree TR, Rigual NR, Merzianu M, Hauck L, et al. Chronic periodontitis and the incidence of head and neck squamous cell carcinoma. Cancer Epidemiol Biomark Prev. 2009;18:2406–12.CrossRef
32.
Mai X, LaMonte MJ, Hovey KM, Nwizu N, Freudenheim JL, Tezal M, Scannapieco F, Hyland A, Andrews CA, Genco RJ, Wactawski-Wende J. History of periodontal disease diagnosis and lung cancer incidence in the Women's Health Initiative Observational Study. Cancer Causes Control. 2014;25:1045–53.PubMedPubMedCentralCrossRef
33.
Urbaniak C, Cummins J, Brackstone M, Macklaim JM, Gloor GB, Baban CK, Scott L, O'Hanlon DM, Burton JP, Francis KP, et al. Microbiota of human breast tissue. Appl Environ Microbiol. 2014;80:3007–14.PubMedPubMedCentralCrossRef
34.
Freudenheim JL, Genco RJ, LaMonte MJ, Millen AE, Hovey KM, Mai X, Nwizu N, Andrews CA, Wactawski-Wende J. Periodontal Disease and Breast Cancer: Prospective Cohort Study of Postmenopausal Women. Cancer Epidemiol Biomark Prev. 2016;25:43–50.CrossRef
35.
Nwizu NN, Marshall JR, Moysich K, Genco RJ, Hovey KM, Mai X, LaMonte MJ, Freudenheim JL, Wactawski-Wende J. Periodontal Disease and Incident Cancer Risk among Postmenopausal Women: Results from the Women's Health Initiative Observational Cohort. Cancer Epidemiol Biomark Prev. 2017;26:1255–65.CrossRef
36.
Farrell JJ, Zhang L, Zhou H, Chia D, Elashoff D, Akin D, Paster BJ, Joshipura K, Wong DT. Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer. Gut. 2012;61:582–8.PubMedCrossRef
37.
Meyer MS, Joshipura K, Giovannucci E, Michaud DS. A review of the relationship between tooth loss, periodontal disease, and cancer. Cancer Causes Control. 2008;19:895–907.PubMedPubMedCentralCrossRef
38.
Stolzenberg-Solomon RZ, Dodd KW, Blaser MJ, Virtamo J, Taylor PR, Albanes D. Tooth loss, pancreatic cancer, and Helicobacter pylori. Am J Clin Nutr. 2003;78:176–81.CrossRefPubMed
39.
Hiraki A, Matsuo K, Suzuki T, Kawase T, Tajima K. Teeth loss and risk of cancer at 14 common sites in Japanese. Cancer Epidemiol Biomark Prev. 2008;17:1222–7.CrossRef
40.
Hayashi C, Gudino CV, Gibson FC 3rd, Genco CA. Review: Pathogen-induced inflammation at sites distant from oral infection: bacterial persistence and induction of cell-specific innate immune inflammatory pathways. Mol Oral Microbiol. 2010;25:305–16.PubMedPubMedCentralCrossRef
41.
Brook I, Frazier EH. Microbiological analysis of pancreatic abscess. Clin Infect Dis. 1996;22:384–5.PubMedCrossRef
42.
Jacob JA. Study Links Periodontal Disease Bacteria to Pancreatic Cancer Risk. JAMA. 2016;315:2653–4.PubMedCrossRef
43.
Fan X, Alekseyenko AV, Wu J, Peters BA, Jacobs EJ, Gapstur SM, Purdue MP, Abnet CC, Stolzenberg-Solomon R, Miller G, et al. Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study. Gut. 2018;67:120–7.PubMedCrossRef
44.
Barton CM, Staddon SL, Hughes CM, Hall PA, O'Sullivan C, Kloppel G, Theis B, Russell RC, Neoptolemos J, Williamson RC, et al. Abnormalities of the p53 tumour suppressor gene in human pancreatic cancer. Br J Cancer. 1991;64:1076–82.PubMedPubMedCentralCrossRef
45.
Liu L, Wang K, Zhu ZM, Shao JH. Associations between P53 Arg72Pro and development of digestive tract cancers: a meta-analysis. Arch Med Res. 2011;42:60–9.PubMedCrossRef
46.
Prassolov VS, Sakamoto H, Nishimura S, Terada M, Sugimura T. Activation of c-Ki-ras gene in human pancreatic cancer. Jpn J Cancer Res. 1985;76:792–5.PubMed
47.
Watanabe H, Miyagi C, Yamaguchi Y, Satomura Y, Ohta H, Motoo Y, Okai T, Yoshimura T, Tsuji Y, Sawabu N. Detection of K-ras point mutations at codon 12 in pancreatic juice for the diagnosis of pancreatic cancer by hybridization protection assay: a simple method for the determination of the types of point mutation. Jpn J Cancer Res. 1996;87:466–74.PubMedPubMedCentralCrossRef
48.
Evans T, Faircloth M, Deery A, Thomas V, Turner A, Dalgleish A. Analysis of K-ras gene mutations in human pancreatic cancer cell lines and in bile samples from patients with pancreatic and biliary cancers. Oncol Rep. 1997;4:1373–81.PubMed
49.
Sinn BV, Striefler JK, Rudl MA, Lehmann A, Bahra M, Denkert C, Sinn M, Stieler J, Klauschen F, Budczies J, et al. KRAS mutations in codon 12 or 13 are associated with worse prognosis in pancreatic ductal adenocarcinoma. Pancreas. 2014;43:578–83.PubMedCrossRef
50.
51.
52.
53.
Tribble GD, Kerr JE, Wang BY. Genetic diversity in the oral pathogen Porphyromonas gingivalis: molecular mechanisms and biological consequences. Future Microbiol. 2013;8:607–20.PubMedCrossRef
54.
Aliyu SH, Marriott RK, Curran MD, Parmar S, Bentley N, Brown NM, Brazier JS, Ludlam H. Real-time PCR investigation into the importance of Fusobacterium necrophorum as a cause of acute pharyngitis in general practice. J Med Microbiol. 2004;53:1029–35.PubMedCrossRef
55.
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. 2013;14:207–15.PubMedPubMedCentralCrossRef
56.
Yu T, Guo F, Yu Y, Sun T, Ma D, Han J, Qian Y, Kryczek I, Sun D, Nagarsheth N, et al. Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy. Cell. 2017;170:548–563 e516.PubMedPubMedCentralCrossRef
57.
Maisonneuve P, Lowenfels AB. Risk factors for pancreatic cancer: a summary review of meta-analytical studies. Int J Epidemiol. 2015;44:186–98.PubMedCrossRef
58.
Mishra AK, Dubey V, Ghosh AR. Obesity: An overview of possible role(s) of gut hormones, lipid sensing and gut microbiota. Metabolism. 2016;65:48–65.PubMedCrossRef
59.
Fritz S, Hackert T, Hartwig W, Rossmanith F, Strobel O, Schneider L, Will-Schweiger K, Kommerell M, Buchler MW, Werner J. Bacterial translocation and infected pancreatic necrosis in acute necrotizing pancreatitis derives from small bowel rather than from colon. Am J Surg. 2010;200:111–7.PubMedCrossRef
60.
Pushalkar S, Hundeyin M, Daley D, Zambirinis CP, Kurz E, Mishra A, Mohan N, Aykut B, Usyk M, Torres LE, et al. The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression. Cancer Discov. 2018;8:403–16.PubMedPubMedCentralCrossRef
61.
Sethi V, Kurtom S, Tarique M, Lavania S, Malchiodi Z, Hellmund L, Zhang L, Sharma U, Giri B, Garg B, et al. Gut Microbiota Promotes Tumor Growth in Mice by Modulating Immune Response. Gastroenterology. 2018;155:33–37 e36.PubMedCrossRef
62.
Raderer M, Wrba F, Kornek G, Maca T, Koller DY, Weinlaender G, Hejna M, Scheithauer W. Association between Helicobacter pylori infection and pancreatic cancer. Oncology. 1998;55:16–9.PubMedCrossRef
63.
Stolzenberg-Solomon RZ, Blaser MJ, Limburg PJ, Perez-Perez G, Taylor PR, Virtamo J, Albanes D, Study A. Helicobacter pylori seropositivity as a risk factor for pancreatic cancer. J Natl Cancer Inst. 2001;93:937–41.PubMedCrossRef
64.
Risch HA, Yu H, Lu L, Kidd MS. ABO blood group, Helicobacter pylori seropositivity, and risk of pancreatic cancer: a case-control study. J Natl Cancer Inst. 2010;102:502–5.PubMedPubMedCentralCrossRef
65.
Lindkvist B, Johansen D, Borgstrom A, Manjer J. A prospective study of Helicobacter pylori in relation to the risk for pancreatic cancer. BMC Cancer. 2008;8:321.PubMedPubMedCentralCrossRef
66.
Bao Y, Spiegelman D, Li R, Giovannucci E, Fuchs CS, Michaud DS. History of peptic ulcer disease and pancreatic cancer risk in men. Gastroenterology. 2010;138:541–9.PubMedCrossRef
67.
Trikudanathan G, Philip A, Dasanu CA, Baker WL. Association between Helicobacter pylori infection and pancreatic cancer. A cumulative meta-analysis. JOP. 2011;12:26–31.PubMed
68.
69.
Schulte A, Pandeya N, Fawcett J, Fritschi L, Risch HA, Webb PM, Whiteman DC, Neale RE. Association between Helicobacter pylori and pancreatic cancer risk: a meta-analysis. Cancer Causes Control. 2015;26:1027–35.PubMedCrossRef
70.
de Martel C, Llosa AE, Friedman GD, Vogelman JH, Orentreich N, Stolzenberg-Solomon RZ, Parsonnet J. Helicobacter pylori infection and development of pancreatic cancer. Cancer Epidemiol Biomark Prev. 2008;17:1188–94.CrossRef
71.
Gawin A, Wex T, Lawniczak M, Malfertheiner P, Starzynska T. Helicobacter pylori infection in pancreatic cancer. Pol Merkur Lekarski. 2012;32:103–7.PubMed
72.
Yu G, Murphy G, Michel A, Weinstein SJ, Mannisto S, Albanes D, Pawlita M, Stolzenberg-Solomon RZ. Seropositivity to Helicobacter pylori and risk of pancreatic cancer. Cancer Epidemiol Biomark Prev. 2013;22:2416–9.CrossRef
73.
Chen XZ, Wang R, Chen HN, Hu JK. Cytotoxin-Associated Gene A-Negative Strains of Helicobacter pylori as a Potential Risk Factor of Pancreatic Cancer: A Meta-Analysis Based on Nested Case-Control Studies. Pancreas. 2015;44:1340–4.PubMedCrossRef
74.
Wang Y, Zhang FC, Wang YJ. Helicobacter pylori and pancreatic cancer risk: a meta- analysis based on 2,049 cases and 2,861 controls. Asian Pac J Cancer Prev. 2014;15:4449–54.PubMedCrossRef
75.
Risch HA, Lu L, Kidd MS, Wang J, Zhang W, Ni Q, Gao YT, Yu H. Helicobacter pylori seropositivities and risk of pancreatic carcinoma. Cancer Epidemiol Biomark Prev. 2014;23:172–8.CrossRef
76.
Kalaf EA, Al-Khafaji ZM, Yassen NY, Al-Abbudi FA, Sadwen SN. Study of the cytoxin-associated gene a (CagA gene) in Helicobacter pylori using gastric biopsies of Iraqi patients. Saudi J Gastroenterol. 2013;19:69–74.PubMedPubMedCentralCrossRef
77.
Chen S, Duan G, Zhang R, Fan Q. Helicobacter pylori cytotoxin-associated gene A protein upregulates alpha-enolase expression via Src/MEK/ERK pathway: implication for progression of gastric cancer. Int J Oncol. 2014;45:764–70.PubMedCrossRef
78.
Risch HA. Pancreatic cancer: Helicobacter pylori colonization, N-nitrosamine exposures, and ABO blood group. Mol Carcinog. 2012;51:109–18.PubMedCrossRef
79.
Jesnowski R, Isaksson B, Mohrcke C, Bertsch C, Bulajic M, Schneider-Brachert W, Kloppel G, Lowenfels AB, Maisonneuve P, Lohr JM. Helicobacter pylori in autoimmune pancreatitis and pancreatic carcinoma. Pancreatology. 2010;10:462–6.PubMedCrossRef
80.
Luo J, Nordenvall C, Nyren O, Adami HO, Permert J, Ye W. The risk of pancreatic cancer in patients with gastric or duodenal ulcer disease. Int J Cancer. 2007;120:368–72.PubMedCrossRef
81.
Shimoda T, Shikata T, Karasawa T, Tsukagoshi S, Yoshimura M, Sakurai I. Light microscopic localization of hepatitis B virus antigens in the human pancreas. Possibility of multiplication of hepatitis B virus in the human pancreas. Gastroenterology. 1981;81:998–1005.PubMed
82.
Yoshimura M, Sakurai I, Shimoda T, Abe K, Okano T, Shikata T. Detection of HBsAg in the pancreas. Acta Pathol Jpn. 1981;31:711–7.PubMed
83.
Dejean A, Lugassy C, Zafrani S, Tiollais P, Brechot C. Detection of hepatitis B virus DNA in pancreas, kidney and skin of two human carriers of the virus. J Gen Virol. 1984;65 ( Pt 3:651–5.PubMedCrossRef
84.
Hohenberger P. The pancreas as target organ for hepatitis B virus--immunohistological detection of HBsAg in pancreatic carcinoma and chronic pancreatitis. Leber Magen Darm. 1985;15:58–63.PubMed
85.
Jin Y, Gao H, Chen H, Wang J, Chen M, Li G, Wang L, Gu J, Tu H. Identification and impact of hepatitis B virus DNA and antigens in pancreatic cancer tissues and adjacent non-cancerous tissues. Cancer Lett. 2013;335:447–54.PubMedCrossRef
86.
Chen Y, Bai X, Zhang Q, Wen L, Su W, Fu Q, Sun X, Lou Y, Yang J, Zhang J, et al. The hepatitis B virus X protein promotes pancreatic cancer through modulation of the PI3K/AKT signaling pathway. Cancer Lett. 2016;380:98–105.PubMedCrossRef
87.
Fiorino S, Visani M, Acquaviva G, Fornelli A, Masetti M, Cuppini A, Bacchi-Reggiani ML, Jovine E, Tallini G, Pession A, de Biase D. Search for HBV and HCV Genome in Cancer Cells of Pancreatic Tumors. Pancreas. 2016;45:e12–4.PubMedCrossRef
88.
Sundquist K, Sundquist J, Ji J. Risk of hepatocellular carcinoma and cancers at other sites among patients diagnosed with chronic hepatitis B virus infection in Sweden. J Med Virol. 2014;86:18–22.PubMedCrossRef
89.
Kamiza AB, Su FH, Wang WC, Sung FC, Chang SN, Yeh CC. Chronic hepatitis infection is associated with extrahepatic cancer development: a nationwide population-based study in Taiwan. BMC Cancer. 2016;16:861.PubMedPubMedCentralCrossRef
90.
Kwok RM, Tran TT. Hepatitis B and Risk of Non-Hepatocellular Carcinoma Malignancy. Clin Liver Dis. 2016;20:693–702.PubMedCrossRef
91.
Wei XL, Luo HY, Li CF, Jin Y, Zeng ZL, Ju HQ, Wu QN, Wang Y, Mao MJ, Liu WL, et al. Hepatitis B virus infection is associated with younger median age at diagnosis and death in cancers. Int J Cancer. 2017;141:152–9.PubMedCrossRef
92.
Fiorino S. HBV and HCV infection and pancreatic ductal adenocarcinoma. Hepatobiliary Pancreat Dis Int. 2013;12:570–4.PubMedCrossRef
93.
Taranto D, Carrato A, Romano M, Maio G, Izzo CM, Del Vecchio Blanco C. Mild pancreatic damage in acute viral hepatitis. Digestion. 1989;42:93–7.PubMedCrossRef
94.
Katakura Y, Yotsuyanagi H, Hashizume K, Okuse C, Okuse N, Nishikawa K, Suzuki M, Iino S, Itoh F. Pancreatic involvement in chronic viral hepatitis. World J Gastroenterol. 2005;11:3508–13.PubMedPubMedCentralCrossRef
95.
Hoefs JC, Renner IG, Askhcavai M, Redeker AG. Hepatitis B surface antigen in pancreatic and biliary secretions. Gastroenterology. 1980;79:191–4.PubMedCrossRef
96.
Ben Q, Li Z, Liu C, Cai Q, Yuan Y, Wang K, Xiao L, Gao J, Zhang H. Hepatitis B virus status and risk of pancreatic ductal adenocarcinoma: a case-control study from China. Pancreas. 2012;41:435–40.PubMedCrossRef
97.
Hassan MM, Li D, El-Deeb AS, Wolff RA, Bondy ML, Davila M, Abbruzzese JL. Association between hepatitis B virus and pancreatic cancer. J Clin Oncol. 2008;26:4557–62.PubMedPubMedCentralCrossRef
98.
Fiorino S, Chili E, Bacchi-Reggiani L, Masetti M, Deleonardi G, Grondona AG, Silvestri T, Magrini E, Zanini N, Cuppini A, et al. Association between hepatitis B or hepatitis C virus infection and risk of pancreatic adenocarcinoma development: a systematic review and meta-analysis. Pancreatology. 2013;13:147–60.PubMedCrossRef
99.
Li L, Wu B, Yang LB, Yin GC, Liu JY. Chronic hepatitis B virus infection and risk of pancreatic cancer: a meta-analysis. Asian Pac J Cancer Prev. 2013;14:275–9.PubMedCrossRef
100.
Luo G, Hao NB, Hu CJ, Yong X, Lu MH, Cheng BJ, Zhang Y, Yang SM. HBV infection increases the risk of pancreatic cancer: a meta-analysis. Cancer Causes Control. 2013;24:529–37.PubMedCrossRef
101.
Wang Y, Yang S, Song F, Cao S, Yin X, Xie J, Tu X, Xu J, Xu X, Dong X, Lu Z. Hepatitis B virus status and the risk of pancreatic cancer: a meta-analysis. Eur J Cancer Prev. 2013;22:328–34.PubMedCrossRef
102.
Xing S, Li ZW, Tian YF, Zhang LM, Li MQ, Zhou P. Chronic hepatitis virus infection increases the risk of pancreatic cancer: a meta-analysis. Hepatobiliary Pancreat Dis Int. 2013;12:575–83.PubMedCrossRef
103.
Xu JH, Fu JJ, Wang XL, Zhu JY, Ye XH, Chen SD. Hepatitis B or C viral infection and risk of pancreatic cancer: a meta-analysis of observational studies. World J Gastroenterol. 2013;19:4234–41.PubMedPubMedCentralCrossRef
104.
Majumder S, Bockorny B, Baker WL, Dasanu CA. Association between HBsAg positivity and pancreatic cancer: a meta-analysis. J Gastrointest Cancer. 2014;45:347–52.PubMedCrossRef
105.
Iloeje UH, Yang HI, Jen CL, Su J, Wang LY, You SL, Lu SN, Chen CJ. Risk of pancreatic cancer in chronic hepatitis B virus infection: data from the REVEAL-HBV cohort study. Liver Int. 2010;30:423–9.PubMedCrossRef
106.
Wei XL, Qiu MZ, Chen WW, Jin Y, Ren C, Wang F, Luo HY, Wang ZQ, Zhang DS, Wang FH, et al. The status of HBV infection influences metastatic pattern and survival in Chinese patients with pancreatic cancer. J Transl Med. 2013;11:249.PubMedPubMedCentralCrossRef
107.
Wang DS, Chen DL, Ren C, Wang ZQ, Qiu MZ, Luo HY, Zhang DS, Wang FH, Li YH, Xu RH. ABO blood group, hepatitis B viral infection and risk of pancreatic cancer. Int J Cancer. 2012;131:461–8.PubMedCrossRef
108.
Andersen ES, Omland LH, Jepsen P, Krarup H, Christensen PB, Obel N, Weis N, Study DC. Risk of all-type cancer, hepatocellular carcinoma, non-Hodgkin lymphoma and pancreatic cancer in patients infected with hepatitis B virus. J Viral Hepat. 2015;22:828–34.PubMedCrossRef
109.
Fiorino S, Lorenzini S, Masetti M, Deleonardi G, Grondona AG, Silvestri T, Chili E, Del Prete P, Bacchi-Reggiani L, Cuppini A, Jovine E. Hepatitis B and C virus infections as possible risk factor for pancreatic adenocarcinoma. Med Hypotheses. 2012;79:678–97.PubMedCrossRef
110.
Fiorino S, Bacchi-Reggiani L, Pontoriero L, Gallo C, Chili E, Masetti M, Zanini N, Grondona A, Silvestri T, Deleonardi G, et al. Tensegrity model hypothesis: may this paradigm be useful to explain hepatic and pancreatic carcinogenesis in patients with persistent hepatitis B or hepatitis C virus infection? JOP. 2014;15:151–64.PubMed
111.
Sangiorgio L, Attardo T, Gangemi R, Rubino C, Barone M, Lunetta M. Increased frequency of HCV and HBV infection in type 2 diabetic patients. Diabetes Res Clin Pract. 2000;48:147–51.PubMedCrossRef
112.
Maekawa T, Fukaya R, Takamatsu S, Itoyama S, Fukuoka T, Yamada M, Hata T, Nagaoka S, Kawamoto K, Eguchi H, et al. Possible involvement of Enterococcus infection in the pathogenesis of chronic pancreatitis and cancer. Biochem Biophys Res Commun. 2018;506:962-969.PubMedCrossRef
113.
Serra N, Di Carlo P, Gulotta G, d' Arpa F, Giammanco A, Colomba C, Melfa G, Fasciana T, Sergi C. Bactibilia in women affected with diseases of the biliary tract and pancreas. A STROBE guidelines-adherent cross-sectional study in Southern Italy. J Med Microbiol. 2018;67:1090–5.PubMedCrossRef
114.
Tomasiewicz K, Modrzewska R, Lyczak A, Krawczuk G. TT virus infection and pancreatic cancer: relationship or accidental coexistence. World J Gastroenterol. 2005;11:2847–9.PubMedPubMedCentralCrossRef
115.
116.
Olson SH, Satagopan J, Xu Y, Ling L, Leong S, Orlow I, Saldia A, Li P, Nunes P, Madonia V, et al. The oral microbiota in patients with pancreatic cancer, patients with IPMNs, and controls: a pilot study. Cancer Causes Control. 2017;28:959–69.PubMedPubMedCentralCrossRef
117.
Geller LT, Barzily-Rokni M, Danino T, Jonas OH, Shental N, Nejman D, Gavert N, Zwang Y, Cooper ZA, Shee K, et al. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science. 2017;357:1156–60.PubMedPubMedCentralCrossRef
118.
Nilsson HO, Stenram U, Ihse I, Wadstrom T. Helicobacter species ribosomal DNA in the pancreas, stomach and duodenum of pancreatic cancer patients. World J Gastroenterol. 2006;12:3038–43.PubMedPubMedCentralCrossRef
119.
Takayama S, Takahashi H, Matsuo Y, Okada Y, Manabe T. Effects of Helicobacter pylori infection on human pancreatic cancer cell line. Hepatogastroenterology. 2007;54:2387–91.PubMed
120.
Mitsuhashi K, Nosho K, Sukawa Y, Matsunaga Y, Ito M, Kurihara H, Kanno S, Igarashi H, Naito T, Adachi Y, et al. Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis. Oncotarget. 2015;6:7209–20.PubMedPubMedCentral
121.
122.
Lowenfels AB, Maisonneuve P, Cavallini G, Ammann RW, Lankisch PG, Andersen JR, Dimagno EP, Andren-Sandberg A, Domellof L. Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N Engl J Med. 1993;328:1433–7.PubMedCrossRef
123.
124.
Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454:436–44.PubMedCrossRef
125.
Morgillo F, Dallio M, Della Corte CM, Gravina AG, Viscardi G, Loguercio C, Ciardiello F, Federico A. Carcinogenesis as a Result of Multiple Inflammatory and Oxidative Hits: a Comprehensive Review from Tumor Microenvironment to Gut Microbiota. Neoplasia. 2018;20:721–33.PubMedPubMedCentralCrossRef
126.
Guerra C, Schuhmacher AJ, Canamero M, Grippo PJ, Verdaguer L, Perez-Gallego L, Dubus P, Sandgren EP, Barbacid M. Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell. 2007;11:291–302.PubMedCrossRef
127.
Sparmann A, Bar-Sagi D. Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell. 2004;6:447–58.PubMedCrossRef
128.
Schulz MD, Atay C, Heringer J, Romrig FK, Schwitalla S, Aydin B, Ziegler PK, Varga J, Reindl W, Pommerenke C, et al. High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity. Nature. 2014;514:508–12.PubMedPubMedCentralCrossRef
129.
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. 2013;342:967–70.PubMedCrossRefPubMedCentral
130.
131.
132.
Sistigu A, Viaud S, Chaput N, Bracci L, Proietti E, Zitvogel L. Immunomodulatory effects of cyclophosphamide and implementations for vaccine design. Semin Immunopathol. 2011;33:369–83.PubMedCrossRef
133.
Viaud S, Saccheri F, Mignot G, Yamazaki T, Daillere R, Hannani D, Enot DP, Pfirschke C, Engblom C, Pittet MJ, et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science. 2013;342:971–6.PubMedPubMedCentralCrossRef
134.
Vetizou M, Pitt JM, Daillere 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. 2015;350:1079–84.PubMedPubMedCentralCrossRef
135.
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. 2015;350:1084–9.PubMedPubMedCentralCrossRef
136.
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. 2018;359:97–103.PubMedCrossRef
137.
Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre ML, Luke JJ, Gajewski TF. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 2018;359:104–8.PubMedCrossRefPubMedCentral
138.
Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillere R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359:91–7.PubMedCrossRef
139.
140.
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. 2012;209:1671–87.PubMedPubMedCentralCrossRef
141.
Ochi A, Graffeo CS, Zambirinis CP, Rehman A, Hackman M, Fallon N, Barilla RM, Henning JR, Jamal M, Rao R, et al. Toll-like receptor 7 regulates pancreatic carcinogenesis in mice and humans. J Clin Invest. 2012;122:4118–29.PubMedPubMedCentralCrossRef
142.
Ikebe M, Kitaura Y, Nakamura M, Tanaka H, Yamasaki A, Nagai S, Wada J, Yanai K, Koga K, Sato N, et al. Lipopolysaccharide (LPS) increases the invasive ability of pancreatic cancer cells through the TLR4/MyD88 signaling pathway. J Surg Oncol. 2009;100:725–31.PubMedCrossRef
143.
Zhang JJ, Wu HS, Wang L, Tian Y, Zhang JH, Wu HL. Expression and significance of TLR4 and HIF-1alpha in pancreatic ductal adenocarcinoma. World J Gastroenterol. 2010;16:2881–8.PubMedPubMedCentralCrossRef
144.
Ding SP, Li JC, Jin C. A mouse model of severe acute pancreatitis induced with caerulein and lipopolysaccharide. World J Gastroenterol. 2003;9:584–9.PubMedPubMedCentralCrossRef
145.
Sharif R, Dawra R, Wasiluk K, Phillips P, Dudeja V, Kurt-Jones E, Finberg R, Saluja A. Impact of toll-like receptor 4 on the severity of acute pancreatitis and pancreatitis-associated lung injury in mice. Gut. 2009;58:813–9.PubMedCrossRef
146.
Daniluk J, Liu Y, Deng D, Chu J, Huang H, Gaiser S, Cruz-Monserrate Z, Wang H, Ji B, Logsdon CD. An NF-kappaB pathway-mediated positive feedback loop amplifies Ras activity to pathological levels in mice. J Clin Invest. 2012;122:1519–28.PubMedPubMedCentralCrossRef
147.
Riquelme E, Maitra A, McAllister F. Immunotherapy for Pancreatic Cancer: More Than Just a Gut Feeling. Cancer Discov. 2018;8:386–8.PubMedCrossRef
148.
De Monte L, Reni M, Tassi E, Clavenna D, Papa I, Recalde H, Braga M, Di Carlo V, Doglioni C, Protti MP. Intratumor T helper type 2 cell infiltrate correlates with cancer-associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer. J Exp Med. 2011;208:469–78.PubMedPubMedCentralCrossRef
149.
Benakanakere MR, Li Q, Eskan MA, Singh AV, Zhao J, Galicia JC, Stathopoulou P, Knudsen TB, Kinane DF. Modulation of TLR2 protein expression by miR-105 in human oral keratinocytes. J Biol Chem. 2009;284:23107–15.PubMedPubMedCentralCrossRef
150.
Moffatt CE, Lamont RJ. Porphyromonas gingivalis induction of microRNA-203 expression controls suppressor of cytokine signaling 3 in gingival epithelial cells. Infect Immun. 2011;79:2632–7.PubMedPubMedCentralCrossRef
151.
Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, Pettersson S. Host-gut microbiota metabolic interactions. Science. 2012;336:1262–7.PubMedCrossRef
152.
Donohoe DR, Collins LB, Wali A, Bigler R, Sun W, Bultman SJ. The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. Mol Cell. 2012;48:612–26.PubMedPubMedCentralCrossRef
153.
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. 2014;4:1387–97.PubMedPubMedCentralCrossRef
154.
Clarke JM, Topping DL, Bird AR, Young GP, Cobiac L. Effects of high-amylose maize starch and butyrylated high-amylose maize starch on azoxymethane-induced intestinal cancer in rats. Carcinogenesis. 2008;29:2190–4.PubMedPubMedCentralCrossRef
155.
Buda A, Qualtrough D, Jepson MA, Martines D, Paraskeva C, Pignatelli M. Butyrate downregulates alpha2beta1 integrin: a possible role in the induction of apoptosis in colorectal cancer cell lines. Gut. 2003;52:729–34.PubMedPubMedCentralCrossRef
156.
Miko E, Vida A, Kovacs T, Ujlaki G, Trencsenyi G, Marton J, Sari Z, Kovacs P, Boratko A, Hujber Z, et al. Lithocholic acid, a bacterial metabolite reduces breast cancer cell proliferation and aggressiveness. Biochim Biophys Acta Bioenerg. 2018;1859:958–74.PubMedCrossRef
157.
Rogers CJ, Prabhu KS, Vijay-Kumar M. The microbiome and obesity-an established risk for certain types of cancer. Cancer J. 2014;20:176–80.PubMedCrossRef
158.
Djuric Z. Obesity-associated cancer risk: the role of intestinal microbiota in the etiology of the host proinflammatory state. Transl Res. 2017;179:155–67.PubMedCrossRef
159.
Parekh PJ, Balart LA, Johnson DA. The Influence of the Gut Microbiome on Obesity, Metabolic Syndrome and Gastrointestinal Disease. Clin Transl Gastroenterol. 2015;6:e91.PubMedPubMedCentralCrossRef
160.
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. 2013;499:97–101.PubMedCrossRef
161.
Eibl G, Rozengurt E. KRAS, YAP, and obesity in pancreatic cancer: A signaling network with multiple loops. Semin Cancer Biol. 2019;54:50-62.PubMedCrossRef
162.
Thomas H. Pancreatic cancer: Intra-tumour bacteria promote gemcitabine resistance in pancreatic adenocarcinoma. Nat Rev Gastroenterol Hepatol. 2017;14:632.PubMedCrossRef
163.
Klemm F, Joyce JA. Microenvironmental regulation of therapeutic response in cancer. Trends Cell Biol. 2015;25:198–213.PubMedCrossRef
164.
165.
Apte MV, Wilson JS, Lugea A, Pandol SJ. A starring role for stellate cells in the pancreatic cancer microenvironment. Gastroenterology. 2013;144:1210–9.PubMedCrossRef
166.
Tang D, Wang D, Yuan Z, Xue X, Zhang Y, An Y, Chen J, Tu M, Lu Z, Wei J, et al. Persistent activation of pancreatic stellate cells creates a microenvironment favorable for the malignant behavior of pancreatic ductal adenocarcinoma. Int J Cancer. 2013;132:993–1003.PubMedCrossRef
167.
Barbour SE, Nakashima K, Zhang JB, Tangada S, Hahn CL, Schenkein HA, Tew JG. Tobacco and smoking: environmental factors that modify the host response (immune system) and have an impact on periodontal health. Crit Rev Oral Biol Med. 1997;8:437–60.PubMedCrossRef
168.
Metadata
Title
The microbiota and microbiome in pancreatic cancer: more influential than expected
Authors
Miao-Yan Wei
Si Shi
Chen Liang
Qing-Cai Meng
Jie Hua
Yi-Yin Zhang
Jiang Liu
Bo Zhang
Jin Xu
Xian-Jun Yu
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2019
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-019-1008-0

Other articles of this Issue 1/2019

Molecular Cancer 1/2019 Go to the issue

Review

Bevacizumab treatment for radiation brain necrosis: mechanism, efficacy and issues

Research

Long noncoding RNA Pvt1 regulates the immunosuppression activity of granulocytic myeloid-derived suppressor cells in tumor-bearing mice

Review

Long non-coding RNAs in Oral squamous cell carcinoma: biologic function, mechanisms and clinical implications

Research

Exosome-mediated secretion of LOXL4 promotes hepatocellular carcinoma cell invasion and metastasis

Research

Circular RNA circTADA2A promotes osteosarcoma progression and metastasis by sponging miR-203a-3p and regulating CREB3 expression

Review

Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits