Hanyang Med Rev.  2018 Jun;38(2):80-84. 10.7599/hmr.2018.38.2.80.

Microbiome of Hepatobiliary Diseases

• Kim Y
• Choi D

• KMID: 2431303
• DOI: http://doi.org/10.7599/hmr.2018.38.2.80

Abstract

The microbiome, which has been defined as "˜the ecological community of commensal, symbiotic and pathogenic microorganisms that share our body space, may be distinguished from the microbiota as it includes the collective genomes. An increasing level of evidence reveals that the human microbiome plays a major role in health. For this reason, it is often referred to as the "˜forgotten organ.' All surfaces of the human body that are exposed to the environment are colonized, including skin, respiratory system, urogenital tract and gastrointestinal (GI) tract, totaling at least 100 trillion microbial cells. The known roles of the GI microbiome include metabolic functions, synthesis functions, and immune roles. Recent studies indicate that the human gut microbiome plays a significant role in health and disease. Dysbiosis, defined as a pathological imbalance in a microbial community, is becoming increasingly appreciated as a "˜central environmental factor' that is both associated with complex phenotypes and affected by host genetics, diet, and antibiotic use. More recently, a link has been established between the dysmetabolism of bile acids (BAs) in the gut and the gut-liver axis, and this relationship with the microbiome has been highlighted. This review summarizes the microbiome of the hepatobiliary system and how microbiome is related to diseases of the liver and biliary tract.

Keyword

Microbiome; Liver; Gallbladder; Pancreas; Cancer

MeSH Terms

Bile Acids and Salts
Biliary Tract
Biota
Colon
Diet
Dysbiosis
Gallbladder
Gastrointestinal Microbiome
Genetics
Genome
Human Body
Humans
Liver
Microbiota*
Pancreas
Phenotype
Respiratory System
Skin
Bile Acids and Salts

Reference

1. Bruix J, Gores GJ, Mazzaferro V. Hepatocellular carcinoma: clinical frontiers and perspectives. Gut. 2014; 63(5):844–855.

2. Ho J, et al. Translational genomics in pancreatic ductal adenocarcinoma: A review with re-analysis of TCGA dataset. Semin Cancer Biol. 2018.

3. Salem AA, Mackenzie GG. Pancreatic cancer: A critical review of dietary risk. Nutr Res. 2018; 52:1–13.

4. Shibata T, Arai Y, Totoki Y. Totoki, Molecular genomic landscapes of hepatobiliary cancer. Cancer Sci. 2018; 109(5):1282–1291.

5. Hooper LV, Gordon JI. Commensal host-bacterial relationships in the gut. Science. 2001; 292(5519):1115–1118.

6. Kostic AD, Xavier RJ, Gevers D, The microbiome. current status and the future ahead. Gastroenterology. 2014; 146(6):1489–1499.

7. Hollister EB, Gao C, Versalovic J. Compositional and functional features of the gastrointestinal microbiome and their effects on human health. Gastroenterology. 2014; 146(6):1449–1458.

8. Moore PS, Chang Y. Why do viruses cause cancer? Highlights of the first century of human tumour virology. Nat Rev Cancer. 2010; 10(12):878–889.

9. Schwabe RF, Jobin C. The microbiome and cancer. Nat Rev Cancer. 2013; 13(11):800–812.

10. Abreu MT, Peek RM Jr. Gastrointestinal malignancy and the microbiome. Gastroenterology. 2014; 146(6):1534–1546.e3.

11. Szabo G. Gut-liver axis in alcoholic liver disease. Gastroenterology. 2015; 148(1):30–36.

12. Kamsa-ard S, et al. Risk Factors for Cholangiocarcinoma in Thailand: A Systematic Review and Meta-Analysis. Asian Pac J Cancer Prev. 2018; 19(3):605–614.

13. Schnabl B, Brenner DA. Interactions between the intestinal microbiome and liver diseases. Gastroenterology. 2014; 146(6):1513–1524.

14. Younossi ZM, et al. The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. Hepatology. 2016; 64(5):1577–1586.

15. Spengler EK, Loomba R. Recommendations for Diagnosis, Referral for Liver Biopsy, and Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. Mayo Clin Proc. 2015; 90(9):1233–1246.

16. Loomba R, et al. Association between diabetes, family history of diabetes, and risk of nonalcoholic steatohepatitis and fibrosis. Hepatology. 2012; 56(3):943–951.

17. Doycheva I, et al. Non-invasive screening of diabetics in primary care for NAFLD and advanced fibrosis by MRI and MRE. Aliment Pharmacol Ther. 2016; 43(1):83–95.

18. Loomba R, et al. Heritability of Hepatic Fibrosis and Steatosis Based on a Prospective Twin Study. Gastroenterology. 2015; 149(7):1784–1793.

19. Cui J, et al. Shared genetic effects between hepatic steatosis and fibrosis: A prospective twin study. Hepatology. 2016; 64(5):1547–1558.

20. Caussy C, et al. Nonalcoholic fatty liver disease with cirrhosis increases familial risk for advanced fibrosis. J Clin Invest. 2017; 127(7):2697–2704.

21. Gao B, Bataller R. Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology. 2011; 141(5):1572–1585.

22. Wieland A, et al. Systematic review: microbial dysbiosis and nonalcoholic fatty liver disease. Aliment Pharmacol Ther. 2015; 42(9):1051–1063.

23. Boursier J, 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. 2016; 63(3):764–775.

24. Loomba R, et al. Gut Microbiome-Based Metagenomic Signature for Non-invasive Detection of Advanced Fibrosis in Human Nonalcoholic Fatty Liver Disease. Cell Metab. 2017; 25(5):1054–1062.e5.

25. Mouzaki M, et al. Bile Acids and Dysbiosis in Non-Alcoholic Fatty Liver Disease. PLoS One. 2016; 11(5):e0151829.

26. Yan AW, et al. Enteric dysbiosis associated with a mouse model of alcoholic liver disease. Hepatology. 2011; 53(1):96–105.

27. Ferrere G, et al. Fecal microbiota manipulation prevents dysbiosis and alcohol-induced liver injury in mice. J Hepatol. 2017; 66(4):806–815.

28. Mutlu EA, et al. Colonic microbiome is altered in alcoholism. Am J Physiol Gastrointest Liver Physiol. 2012; 302(9):G966–G978.

29. Tuomisto S, et al. Changes in gut bacterial populations and their translocation into liver and ascites in alcoholic liver cirrhotics. BMC Gastroenterol. 2014; 14:40.

30. Chen Y, et al. Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology. 2011; 54(2):562–572.

31. Kirpich IA, et al. Probiotics restore bowel flora and improve liver enzymes in human alcohol-induced liver injury: a pilot study. Alcohol. 2008; 42(8):675–682.

32. Leclercq S, et al. Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity. Proc Natl Acad Sci U S A. 2014; 111(42):E4485–E4493.

33. Yang AM, et al. Intestinal fungi contribute to development of alcoholic liver disease. J Clin Invest. 2017; 127(7):2829–2841.

34. Bajaj JS, et al. Gut Microbiota Alterations can predict Hospitalizations in Cirrhosis Independent of Diabetes Mellitus. Sci Rep. 2015; 5:18559.

35. Jun DW, et al. Association between small intestinal bacterial overgrowth and peripheral bacterial DNA in cirrhotic patients. Dig Dis Sci. 2010; 55(5):1465–1471.

36. Yao J, et al. Nutrition status and small intestinal bacterial overgrowth in patients with virus-related cirrhosis. Asia Pac J Clin Nutr. 2016; 25(2):283–291.

37. Chen Y, et al. Dysbiosis of small intestinal microbiota in liver cirrhosis and its association with etiology. Sci Rep. 2016; 6:34055.

38. Qin N, et al. Alterations of the human gut microbiome in liver cirrhosis. Nature. 2014; 513(7516):59–64.

39. Bajaj JS, et al. Fungal dysbiosis in cirrhosis. Gut. 2018; 67(6):1146–1154.

40. Yoshimoto S, et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature. 2013; 499(7456):97–101.

41. Xie G, et al. Distinctly altered gut microbiota in the progression of liver disease. Oncotarget. 2016; 7(15):19355–19366.

42. Grat M, et al. Relevance of Pre-Transplant alpha-fetoprotein Dynamics in Liver Transplantation for Hepatocellular Cancer. Ann Transplant. 2016; 21:115–124.

43. Fox JG, et al. Gut microbes define liver cancer risk in mice exposed to chemical and viral transgenic hepatocarcinogens. Gut. 2010; 59(1):88–97.

44. Rogers AB. Distance burning: how gut microbes promote extraintestinal cancers. Gut Microbes. 2011; 2(1):52–57.

45. Huang Y, et al. Identification of helicobacter species in human liver samples from patients with primary hepatocellular carcinoma. J Clin Pathol. 2004; 57(12):1273–1277.

46. Kruttgen A, et al. Study on the association of Helicobacter species with viral hepatitis-induced hepatocellular carcinoma. Gut Microbes. 2012; 3(3):228–233.

47. Ferlay J, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015; 136(5):E359–E386.

48. Siegel R, et al. Cancer statistics, 2014. CA Cancer J Clin. 2014; 64(1):9–29.

49. Jung KW, et al. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2011. Cancer Res Treat. 2014; 46(2):109–123.

50. Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: geographical distribution and risk factors. Int J Cancer. 2006; 118(7):1591–1602.

51. Boutros C, et al. Gallbladder cancer: past, present and an uncertain future. Surg Oncol. 2012; 21(4):e183–e191.

52. Nagaraja V, Eslick GD. Systematic review with meta-analysis: the relationship between chronic Salmonella typhi carrier status and gall-bladder cancer. Aliment Pharmacol Ther. 2014; 39(8):745–750.

53. Scanu T, et al. Salmonella Manipulation of Host Signaling Pathways Provokes Cellular Transformation Associated with Gallbladder Carcinoma. Cell Host Microbe. 2015; 17(6):763–774.

54. Gonzalez-Escobedo G, La Perle KM, Gunn JS. Histopathological analysis of Salmonella chronic carriage in the mouse hepatopancreatobiliary system. PLoS One. 2013; 8(12):e84058.

55. Takayama S, et al. Effect of Helicobacter bilis infection on human bile duct cancer cells. Dig Dis Sci. 2010; 55(7):1905–1910.