Gut microbial dysbiosis associates hepatocellular carcinoma via the gut-liver axis

Hepatobiliary and Pancreatic Diseases International

Volumn 18, Issue 1, 2019, Pages 19-27

  Jiang, Jian Wen ^a,b   Chen, Xin Hua ^a,b   Ren, Zhigang ^c   Zheng, Shu Sen ^a,b  

^a ZHEJIANG UNIVERSITY SCHOOL OF MEDICINE   (China)

^b ZHEJIANG UNIVERSITY   (China)

^c THE FIRST AFFILIATED HOSPITAL OF ZHENGZHOU UNIVERSITY   (China)

Author keywords

Gut microbiota; Gut liver axis; Hepatocellular carcinoma; Lipopolysaccharide; Toll like receptor 4

Indexed keywords

TOLL LIKE RECEPTOR 4;

ALCOHOL LIVER DISEASE; CANCER GROWTH; CHRONIC LIVER DISEASE; DISEASE ASSOCIATION; DYSBIOSIS; GENETIC ASSOCIATION; HEPATITIS; HUMAN; INTESTINE FLORA; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; LIVER FUNCTION; METABOLOMICS; NONALCOHOLIC FATTY LIVER; NONHUMAN; PATHOLOGICAL ANATOMY; PRECANCER; REVIEW; TRANSLATIONAL RESEARCH; ANIMAL; CELL TRANSFORMATION; HEPATITIS B; HOST PATHOGEN INTERACTION; LIVER; LIVER TUMOR; METABOLISM; MICROBIOLOGY; PATHOLOGY; PROGNOSIS; RISK FACTOR; SIGNAL TRANSDUCTION; VIROLOGY;

ANIMALS; CARCINOMA, HEPATOCELLULAR; CELL TRANSFORMATION, NEOPLASTIC; DYSBIOSIS; GASTROINTESTINAL MICROBIOME; HEPATITIS B; HOST-PATHOGEN INTERACTIONS; HUMANS; LIVER; LIVER NEOPLASMS; PROGNOSIS; RISK FACTORS; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTOR 4;

EID: 85057859945     PISSN: 14993872     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.hbpd.2018.11.002     Document Type: Review

References (85)

1. Chen, W, Zheng, R, Baade, PD, Zhang, S, Zeng, H, Bray, F, et al. Cancer statistics in China, 2015. CA Cancer J Clin 66 (2016), 115–132.
2. El-Serag, HB, Hepatocellular carcinoma. N Engl J Med 365 (2011), 1118–1127.
3. Welzel, TM, Graubard, BI, Quraishi, S, Zeuzem, S, Davila, JA, El-Serag, HB, et al. Population-attributable fractions of risk factors for hepatocellular carcinoma in the United States. Am J Gastroenterol 108 (2013), 1314–1321.
4. Kamada, N, Seo, SU, Chen, GY, Núñez, G, Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol 13 (2013), 321–335.
5. Nenci, A, Becker, C, Wullaert, A, Gareus, R, van Loo, G, Danese, S, et al. Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature 446 (2007), 557–561.
6. Cani, PD, Delzenne, NM, The role of the gut microbiota in energy metabolism and metabolic disease. Curr Pharm Des 15 (2009), 1546–1558.
7. Bäckhed, F, Ley, RE, Sonnenburg, JL, Peterson, DA, Gordon, JI, Host-bacterial mutualism in the human intestine. Science 307 (2005), 1915–1920.
8. Eckburg, PB, Bik, EM, Bernstein, CN, Purdom, E, Dethlefsen, L, Sargent, M, et al. Diversity of the human intestinal microbial flora. Science 308 (2005), 1635–1638.
9. Chassaing, B, Etienne-Mesmin, L, Gewirtz, AT, Microbiota-liver axis in hepatic disease. Hepatology 59 (2014), 328–339.
10. Ren, Z, Li, A, Jiang, J, Zhou, L, Yu, Z, Lu, H, et al. Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma. Gut, 2018 Jul 25. pii: gutjnl-2017-315084.
11. Marshall, JC, The gut as a potential trigger of exercise-induced inflammatory responses. Can J Physiol Pharmacol 76 (1998), 479–484.
12. Szabo, G, Bala, S, Petrasek, J, Gattu, A, Gut-liver axis and sensing microbes. Dig Dis 28 (2010), 737–744.
13. Nakao, A, Taki, S, Yasui, M, Kimura, Y, Nonami, T, Harada, A, et al. The fate of intravenously injected endotoxin in normal rats and in rats with liver failure. Hepatology 19 (1994), 1251–1256.
14. Medvedev, AE, Lentschat, A, Wahl, LM, Golenbock, DT, Vogel, SN, Dysregulation of LPS-induced Toll-like receptor 4-MyD88 complex formation and IL-1 receptor-associated kinase 1 activation in endotoxin-tolerant cells. J Immunol 169 (2002), 5209–5216.
15. Miettinen, TA, Lipid absorption, bile acids, and cholesterol metabolism in patients with chronic liver disease. Gut 13 (1972), 682–689.
16. Gunnarsdottir, SA, Sadik, R, Shev, S, Simrén, M, Sjövall, H, Stotzer, PO, et al. Small intestinal motility disturbances and bacterial overgrowth in patients with liver cirrhosis and portal hypertension. Am J Gastroenterol 98 (2003), 1362–1370.
17. Yajima, S, Morisaki, H, Serita, R, Suzuki, T, Katori, N, Asahara, T, et al. Tumor necrosis factor-alpha mediates hyperglycemia-augmented gut barrier dysfunction in endotoxemia. Crit Care Med 37 (2009), 1024–1030.
18. Seki, E, Brenner, DA, Toll-like receptors and adaptor molecules in liver disease: update. Hepatology 48 (2008), 322–335.
19. Wiest, R, Garcia-Tsao, G, Bacterial translocation (BT) in cirrhosis. Hepatology 41 (2005), 422–433.
20. Frasinariu, OE, Ceccarelli, S, Alisi, A, Moraru, E, Nobili, V, Gut-liver axis and fibrosis in nonalcoholic fatty liver disease: an input for novel therapies. Dig Liver Dis 45 (2013), 543–551.
21. Ren, Z, Cui, G, Lu, H, Chen, X, Jiang, J, Liu, H, et al. Liver ischemic preconditioning (IPC) improves intestinal microbiota following liver transplantation in rats through 16 s rDNA-based analysis of microbial structure shift. PLoS One, 8, 2013, e75950.
22. Lu, H, Wu, Z, Xu, W, Yang, J, Chen, Y, Li, L, Intestinal microbiota was assessed in cirrhotic patients with hepatitis B virus infection. Intestinal microbiota of HBV cirrhotic patients. Microb Ecol 61 (2011), 693–703.
23. Mutlu, EA, Gillevet, PM, Rangwala, H, Sikaroodi, M, Naqvi, A, Engen, PA, et al. Colonic microbiome is altered in alcoholism. Am J Physiol Gastrointest Liver Physiol 302 (2012), G966–G978.
24. Shen, F, Zheng, RD, Sun, XQ, Ding, WJ, Wang, XY, Fan, JG, Gut microbiota dysbiosis in patients with non-alcoholic fatty liver disease. Hepatobiliary Pancreat Dis Int 16 (2017), 375–381.
25. Wang, J, Wang, Y, Zhang, X, Liu, J, Zhang, Q, Zhao, Y, et al. Gut microbial dysbiosis is associated with altered hepatic functions and serum metabolites in chronic hepatitis B patients. Front Microbiol, 8, 2017, 2222.
26. Gut, JP, Schmitt, S, Bingen, A, Anton, M, Kirn, A, Probable role of endogenous endotoxins in hepatocytolysis during murine hepatitis caused by frog virus 3. J Infect Dis 149 (1984), 621–629.
27. Inoue, T, Nakayama, J, Moriya, K, Kawaratani, H, Momoda, R, Ito, K, et al. Gut dysbiosis associated with hepatitis C virus infection. Clin Infect Dis 67 (2018), 869–877.
28. Yan, AW, Fouts, DE, Brandl, J, Stärkel, P, Torralba, M, Schott, E, et al. Enteric dysbiosis associated with a mouse model of alcoholic liver disease. Hepatology 53 (2011), 96–105.
29. Schnabl, B, Brenner, DA, Interactions between the intestinal microbiome and liver diseases. Gastroenterology 146 (2014), 1513–1524.
30. Hartmann, P, Chen, P, Wang, HJ, Wang, L, McCole, DF, Brandl, K, et al. Deficiency of intestinal mucin-2 ameliorates experimental alcoholic liver disease in mice. Hepatology 58 (2013), 108–119.
31. Kirpich, IA, Solovieva, NV, Leikhter, SN, Shidakova, NA, Lebedeva, OV, Sidorov, PI, et al. Probiotics restore bowel flora and improve liver enzymes in human alcohol-induced liver injury: a pilot study. Alcohol 42 (2008), 675–682.
32. Adachi, Y, Moore, LE, Bradford, BU, Gao, W, Thurman, RG, Antibiotics prevent liver injury in rats following long-term exposure to ethanol. Gastroenterology 108 (1995), 218–224.
33. Ferrier, L, Bérard, F, Debrauwer, L, Chabo, C, Langella, P, Buéno, L, et al. Impairment of the intestinal barrier by ethanol involves enteric microflora and mast cell activation in rodents. Am J Pathol 168 (2006), 1148–1154.
34. Elamin, EE, Masclee, AA, Dekker, J, Jonkers, DM, Ethanol metabolism and its effects on the intestinal epithelial barrier. Nutr Rev 71 (2013), 483–499.
35. Rao, RK, Seth, A, Sheth, P, Recent advances in alcoholic liver disease I. Role of intestinal permeability and endotoxemia in alcoholic liver disease. Am J Physiol Gastrointest Liver Physiol 286 (2004), G881–G884.
36. Mittal, S, El-Serag, HB, Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol 47 (2013), S2–S6.
37. Le Roy, T, Llopis, M, Lepage, P, Bruneau, A, Rabot, S, Bevilacqua, C, et al. Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice. Gut 62 (2013), 1787–1794.
38. Mouzaki, M, Comelli, EM, Arendt, BM, Bonengel, J, Fung, SK, Fischer, SE, et al. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology 58 (2013), 120–127.
39. Zhu, L, Baker, SS, Gill, C, Liu, W, Alkhouri, R, Baker, RD, et al. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH. Hepatology 57 (2013), 601–609.
40. Boursier, J, Mueller, O, Barret, M, Machado, M, Fizanne, L, Araujo-Perez, F, et al. The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology 63 (2016), 764–775.
41. Cabrera, R, Nelson, DR, Review article: the management of hepatocellular carcinoma. Aliment Pharmacol Ther 31 (2010), 461–476.
42. Jia, JD, Further systematize and standardize the diagnosis and treatment of liver cirrhosis. Zhonghua Gan Zang Bing Za Zhi 13 (2005), 401–402.
43. Lin, RS, Lee, FY, Lee, SD, Tsai, YT, Lin, HC, Lu, RH, et al. Endotoxemia in patients with chronic liver diseases: relationship to severity of liver diseases, presence of esophageal varices, and hyperdynamic circulation. J Hepatol 22 (1995), 165–172.
44. Chen, Y, Yang, F, Lu, H, Wang, B, Chen, Y, Lei, D, et al. Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology 54 (2011), 562–572.
45. Qin, N, Yang, F, Li, A, Prifti, E, Chen, Y, Shao, L, et al. Alterations of the human gut microbiome in liver cirrhosis. Nature 513 (2014), 59–64.
46. Bajaj, JS, Heuman, DM, Hylemon, PB, Sanyal, AJ, White, MB, Monteith, P, et al. Altered profile of human gut microbiome is associated with cirrhosis and its complications. J Hepatol 60 (2014), 940–947.
47. Sandler, NG, Koh, C, Roque, A, Eccleston, JL, Siegel, RB, Demino, M, et al. Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection. Gastroenterology 141 (2011), 1220–1230 1230.e1-3.
48. Tranah, TH, Vijay, GK, Ryan, JM, Shawcross, DL, Systemic inflammation and ammonia in hepatic encephalopathy. Metab Brain Dis 28 (2013), 1–5.
49. Bass, NM, Mullen, KD, Sanyal, A, Poordad, F, Neff, G, Leevy, CB, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med 362 (2010), 1071–1081.
50. Fox, JG, Feng, Y, Theve, EJ, Raczynski, AR, Fiala, JL, Doernte, AL, et al. Gut microbes define liver cancer risk in mice exposed to chemical and viral transgenic hepatocarcinogens. Gut 59 (2010), 88–97.
51. Yu, LX, Yan, HX, Liu, Q, Yang, W, Wu, HP, Dong, W, et al. Endotoxin accumulation prevents carcinogen-induced apoptosis and promotes liver tumorigenesis in rodents. Hepatology 52 (2010), 1322–1333.
52. Dapito, DH, Mencin, A, Gwak, GY, Pradere, JP, Jang, MK, Mederacke, I, et al. Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4. Cancer Cell 21 (2012), 504–516.
53. Darnaud, M, Faivre, J, Moniaux, N, Targeting gut flora to prevent progression of hepatocellular carcinoma. J Hepatol 58 (2013), 385–387.
54. Yoshimoto, S, Loo, TM, Atarashi, K, Kanda, H, Sato, S, Oyadomari, S, et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 499 (2013), 97–101.
55. Jang, ES, Yoon, JH, Lee, SH, Lee, SM, Lee, JH, Yu, SJ, et al. Sodium taurocholate cotransporting polypeptide mediates dual actions of deoxycholic acid in human hepatocellular carcinoma cells: enhanced apoptosis versus growth stimulation. J Cancer Res Clin Oncol 140 (2014), 133–144.
56. Horvath, S, Erhart, W, Brosch, M, Ammerpohl, O, von Schönfels, W, Ahrens, M, et al. Obesity accelerates epigenetic aging of human liver. Proc Natl Acad Sci USA 111 (2014), 15538–15543.
57. Coppé, JP, Patil, CK, Rodier, F, Sun, Y, Muñoz, DP, Goldstein, J, et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 6 (2008), 2853–2868.
58. Ohtani, N, Yoshimoto, S, Hara, E, Obesity and cancer: a gut microbial connection. Cancer Res 74 (2014), 1885–1889.
59. Loo, TM, Kamachi, F, Watanabe, Y, Yoshimoto, S, Kanda, H, Arai, Y, et al. Gut microbiota promotes obesity-associated liver cancer through PGE2-mediated suppression of antitumor immunity. Cancer Discov 7 (2017), 522–538.
60. Liu, Y, Crosstalk between liver and gut-holistic integrative hepato-enterology. 2014, People's Medical Publishing House, Beijing, 168–184.
61. Chou, HH, Chien, WH, Wu, LL, Cheng, CH, Chung, CH, Horng, JH, et al. Age-related immune clearance of hepatitis B virus infection requires the establishment of gut microbiota. Proc Natl Acad Sci USA 112 (2015), 2175–2180.
62. Ren, YD, Ye, ZS, Yang, LZ, Jin, LX, Wei, WJ, Deng, YY, et al. Fecal microbiota transplantation induces hepatitis B virus e-antigen (HBeAg) clearance in patients with positive HBeAg after long-term antiviral therapy. Hepatology 65 (2017), 1765–1768.
63. Lu, H, Ren, Z, Li, A, Zhang, H, Jiang, J, Xu, S, et al. Deep sequencing reveals microbiota dysbiosis of tongue coat in patients with liver carcinoma. Sci Rep, 6, 2016, 33142.
64. Grąt, M, Wronka, KM, Krasnodębski, M, Ł, Masior, Lewandowski, Z, Kosińska, I, et al. Profile of gut microbiota associated with the presence of hepatocellular cancer in patients with liver cirrhosis. Transpl Proc 48 (2016), 1687–1691.
65. Lee, MH, Yang, HI, Yuan, Y, L'Italien, G, Chen, CJ, Epidemiology and natural history of hepatitis C virus infection. World J Gastroenterol 20 (2014), 9270–9280.
66. Mitchell, JK, Lemon, SM, McGivern, DR, How do persistent infections with hepatitis C virus cause liver cancer?. Curr Opin Virol 14 (2015), 101–108.
67. Ye, J, Livergood, RS, Peng, G, The role and regulation of human Th17 cells in tumor immunity. Am J Pathol 182 (2013), 10–20.
68. Zhang, JP, Yan, J, Xu, J, Pang, XH, Chen, MS, Li, L, et al. Increased intratumoral IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients. J Hepatol 50 (2009), 980–989.
69. Liao, R, Sun, J, Wu, H, Yi, Y, Wang, JX, He, HW, et al. High expression of IL-17 and IL-17RE associate with poor prognosis of hepatocellular carcinoma. J Exp Clin Cancer Res, 32, 2013, 3.
70. Ivanov, II, Atarashi, K, Manel, N, Brodie, EL, Shima, T, Karaoz, U, et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139 (2009), 485–498.
71. Li, J, Sung, CY, Lee, N, Ni, Y, Pihlajamäki, J, Panagiotou, G, et al. Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice. Proc Natl Acad Sci USA 113 (2016), E1306–E1315.
72. Zhang, HL, Yu, LX, Yang, W, Tang, L, Lin, Y, Wu, H, et al. Profound impact of gut homeostasis on chemically-induced pro-tumorigenic inflammation and hepatocarcinogenesis in rats. J Hepatol 57 (2012), 803–812.
73. Wan, MLY, El-Nezami, H, Targeting gut microbiota in hepatocellular carcinoma: probiotics as a novel therapy. Hepatobiliary Surg Nutr 7 (2018), 11–20.
74. Gagliani, N, Hu, B, Huber, S, Elinav, E, Flavell, RA, The fire within: microbes inflame tumors. Cell 157 (2014), 776–783.
75. Zitvogel, L, Galluzzi, L, Viaud, S, Vétizou, M, Daillère, R, Merad, M, et al. Cancer and the gut microbiota: an unexpected link. Sci Transl Med, 7, 2015 271ps1.
76. Viaud, S, Saccheri, F, Mignot, G, Yamazaki, T, Daillère, R, Hannani, D, et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 342 (2013), 971–976.
77. Daillère, R, Vétizou, M, Waldschmitt, N, Yamazaki, T, Isnard, C, Poirier-Colame, V, et al. Enterococcus hirae and Barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects. Immunity 45 (2016), 931–943.
78. Vétizou, M, Pitt, JM, Daillère, R, Lepage, P, Waldschmitt, N, Flament, C, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350 (2015), 1079–1084.
79. Iida, N, Dzutsev, A, Stewart, CA, Smith, L, Bouladoux, N, Weingarten, RA, et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 342 (2013), 967–970.
80. Thomas, RM, Jobin, C, The microbiome and cancer: Is the 'oncobiome' mirage real?. Trends Cancer 1 (2015), 24–35.
81. Qin, J, Li, R, Raes, J, Arumugam, M, Burgdorf, KS, Manichanh, C, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464 (2010), 59–65.
82. Qin, J, Li, Y, Cai, Z, Li, S, Zhu, J, Zhang, F, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490 (2012), 55–60.
83. Karlsson, FH, Tremaroli, V, Nookaew, I, Bergström, G, Behre, CJ, Fagerberg, B, et al. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 498 (2013), 99–103.
84. Nicholson, JK, Lindon, JC, Holmes, E, 'Metabonomics': understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica 29 (1999), 1181–1189.
85. Integrative HMP (iHMP) Research Network Consortium. The Integrative Human Microbiome Project: dynamic analysis of microbiome-host omics profiles during periods of human health and disease. Cell Host Microbe 16 (2014), 276–289.