Microbial Profiles of Cirrhosis in the Human Small Intestine

Abstract

Purpose of Review

The aim of this review is to summarize the recent literature on associations of small intestinal microbial and bile acid profiles with liver cirrhosis and its complications.

Recent Findings

Recent studies into the duodenal microbiome of patients with cirrhosis have linked the microbiome to certain etiologies of chronic liver disease as well as complications of cirrhosis. In particular, microbial differences in the duodenum of patients with cirrhosis have been linked to the presence of hepatic encephalopathy and varices.

Summary

While the fecal microbiome of patients with liver cirrhosis is well characterized, the small intestinal microbiome of cirrhotic patients is an active area of research. This review focuses on the current understanding of the small intestinal microbiome in human cirrhosis as well as future directions of the field.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.

    Wiest R, Garcia-Tsao G. Bacterial translocation (BT) in cirrhosis. Hepatology. 2005;41:422–33.

    CAS  Article  Google Scholar 

  2. 2.

    Chu H, Duan Y, Yang L, Schnabl B. Small metabolites, possible big changes: a microbiota-centered view of non-alcoholic fatty liver disease. Gut. 2019;68:359–70.

    CAS  Article  Google Scholar 

  3. 3.

    Shalapour S, Lin X-J, Bastian IN, Brain J, Burt AD, Aksenov AA, et al. Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity. Nature. 2017;551:340–5.

    CAS  Article  Google Scholar 

  4. 4.

    Cruz-Ramón V, Chinchilla-López P, Ramírez-Pérez O, Méndez-Sánchez N. Bile acids in nonalcoholic fatty liver disease: new concepts and therapeutic advances. Ann Hepatol. 2017;16:s58–67.

    Article  Google Scholar 

  5. 5.

    Hayashi H, Takahashi R, Nishi T, Sakamoto M, Benno Y. Molecular analysis of jejunal, ileal, caecal and recto-sigmoidal human colonic microbiota using 16S rRNA gene libraries and terminal restriction fragment length polymorphism. J Med Microbiol. 2005;54:1093–101.

    CAS  Article  Google Scholar 

  6. 6.

    Onishi JC, Campbell S, Moreau M, Patel F, Brooks AI, Zhou YX, et al. Bacterial communities in the small intestine respond differently to those in the caecum and colon in mice fed low- and high-fat diets. Microbiology. 2017;163:1189–97.

    CAS  Article  Google Scholar 

  7. 7.

    Zoetendal EG, Raes J, van den Bogert B, Arumugam M, Booijink CCGM, Troost FJ, et al. The human small intestinal microbiota is driven by rapid uptake and conversion of simple carbohydrates. ISME J. 2012;6:1415–26.

    CAS  Article  Google Scholar 

  8. 8.

    Angelakis E, Armougom F, Carrière F, Bachar D, Laugier R, Lagier J-C, et al. A metagenomic investigation of the duodenal microbiota reveals links with obesity. PLoS One. 2015;10:e0137784.

    Article  Google Scholar 

  9. 9.

    Wacklin P, Laurikka P, Lindfors K, Collin P, Salmi T, Lähdeaho ML, et al. Altered duodenal microbiota composition in celiac disease patients suffering from persistent symptoms on a long-term gluten-free diet. Am J Gastroenterol. 2014;109:1933–41.

    CAS  Article  Google Scholar 

  10. 10.

    Steed H, Macfarlane GT, Blackett KL, Macfarlane S, Miller MH, Bahrami B, et al. Bacterial translocation in cirrhosis is not caused by an abnormal small bowel gut microbiota. FEMS Immunol Med Microbiol. 2011;63:346–54.

    CAS  Article  Google Scholar 

  11. 11.

    Costello EK, Lauber CL, Hamady M, Fierer N, Gordon JI, Knight R. Bacterial community variation in human body habitats across space and time. Science. 2009;326:1694–7.

    CAS  Article  Google Scholar 

  12. 12.

    •• Chen Y, Ji F, Guo J, Shi D, Fang D, Li L. Dysbiosis of small intestinal microbiota in liver cirrhosis and its association with etiology. Sci Rep. 2016;6:34055. One of three articles that actually examined the microbiome of cirrhotic patients in the small intestine.

    CAS  Article  Google Scholar 

  13. 13.

    •• Bajaj JS, Kakiyama G, Zhao D, et al. Continued alcohol misuse in human cirrhosis is associated with an impaired gut-liver Axis. Alcohol Clin Exp Res. 2017;41:1857–65. One of three articles that actually examined the microbiome of cirrhotic patients in the small intestine.

    CAS  Article  Google Scholar 

  14. 14.

    •• Jacobs JP, Dong TS, Agopian V, et al. Microbiome and bile acid profiles in duodenal aspirates from patients with liver cirrhosis: the microbiome, microbial markers and liver disease study. Hepatol Res. 2018;48:1108–17. One of three articles that actually examined the microbiome of cirrhotic patients in the small intestine.

    CAS  Article  Google Scholar 

  15. 15.

    Aly AM, Adel A, El-Gendy AO, Essam TM, Aziz RK. Gut microbiome alterations in patients with stage 4 hepatitis C. Gut Pathog. 2016;8:42.

    Article  Google Scholar 

  16. 16.

    Als-Nielsen B, Gluud LL, Gluud C. Nonabsorbable disaccharides for hepatic encephalopathy. Cochrane Database Syst Rev. 2004;4:CD003044.

    Google Scholar 

  17. 17.

    Bass NM, Mullen KD, Sanyal A, Poordad F, Neff G, Leevy CB, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362:1071–81.

    CAS  Article  Google Scholar 

  18. 18.

    Bajaj JS. Review article: potential mechanisms of action of rifaximin in the management of hepatic encephalopathy and other complications of cirrhosis. Aliment Pharmacol Ther. 2016;43(Suppl 1):11–26.

    CAS  Article  Google Scholar 

  19. 19.

    Zhang Y, Feng Y, Cao B, Tian Q. The effect of small intestinal bacterial overgrowth on minimal hepatic encephalopathy in patients with cirrhosis. Arch Med Sci. 2016;12:592–6.

    CAS  Article  Google Scholar 

  20. 20.

    Gupta A, Dhiman RK, Kumari S, Rana S, Agarwal R, Duseja A, et al. Role of small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhotic patients with minimal hepatic encephalopathy. J Hepatol. 2010;53:849–55.

    Article  Google Scholar 

  21. 21.

    • Mullish BH, McDonald JAK, Thursz MR, Marchesi JR. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: a randomized clinical trial. Hepatology. 2017;66:1354–5. The only randomized clinical trial looking at fecal transplant in encephalopathy.

    Article  Google Scholar 

  22. 22.

    Yüksel O, Köklü S, Arhan M, Yolcu OF, Ertuğrul I, Odemiş B, et al. Effects of esophageal varice eradication on portal hypertensive gastropathy and fundal varices: a retrospective and comparative study. Dig Dis Sci. 2006;51:27–30.

    Article  Google Scholar 

  23. 23.

    Scarpellini E, Valenza V, Gabrielli M, Lauritano EC, Perotti G, Merra G, et al. Intestinal permeability in cirrhotic patients with and without spontaneous bacterial peritonitis: is the ring closed? Am J Gastroenterol. 2010;105:323–7.

    Article  Google Scholar 

  24. 24.

    Pascual S, Such J, Esteban A, et al. Intestinal permeability is increased in patients with advanced cirrhosis. Hepatogastroenterology. 2003;50:1482–6.

    PubMed  Google Scholar 

  25. 25.

    Campillo B, Pernet P, Bories PN, Richardet JP, Devanlay M, Aussel C. Intestinal permeability in liver cirrhosis: relationship with severe septic complications. Eur J Gastroenterol Hepatol. 1999;11:755–9.

    CAS  Article  Google Scholar 

  26. 26.

    Parlesak A, Schäfer C, Schütz T, Bode JC, Bode C. Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease. J Hepatol. 2000;32:742–7.

    CAS  Article  Google Scholar 

  27. 27.

    Assimakopoulos SF, Tsamandas AC, Tsiaoussis GI, Karatza E, Triantos C, Vagianos CE, et al. Altered intestinal tight junctions’ expression in patients with liver cirrhosis: a pathogenetic mechanism of intestinal hyperpermeability. Eur J Clin Investig. 2012;42:439–46.

    CAS  Article  Google Scholar 

  28. 28.

    Aranha MM, Cortez-Pinto H, Costa A, da Silva IBM, Camilo ME, de Moura MC, et al. Bile acid levels are increased in the liver of patients with steatohepatitis. Eur J Gastroenterol Hepatol. 2008;20:519–25.

    CAS  Article  Google Scholar 

  29. 29.

    Schnabl B, Brenner DA. Interactions between the intestinal microbiome and liver diseases. Gastroenterology. 2014;146:1513–24.

    CAS  Article  Google Scholar 

  30. 30.

    Ma C, Han M, Heinrich B, Fu Q, Zhang Q, Sandhu M, et al. Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells. Science. 2018;360:eaan5931. https://doi.org/10.1126/science.aan5931.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Fickert P, Wagner M. Biliary bile acids in hepatobiliary injury - what is the link? J Hepatol. 2017;67:619–31.

    CAS  Article  Google Scholar 

  32. 32.

    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. 2013;499:97–101. https://doi.org/10.1038/nature12347.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Chung GE, Yoon J-H, Lee J-H, Kim HY, Myung SJ, Yu SJ, et al. Ursodeoxycholic acid-induced inhibition of DLC1 protein degradation leads to suppression of hepatocellular carcinoma cell growth. Oncol Rep. 2011;25:1739–46.

    CAS  PubMed  Google Scholar 

  34. 34.

    Zhu L, Shan LJ, Liu YJ, Chen D, Xiao XG, Li Y. Ursodeoxycholic acid induces apoptosis of hepatocellular carcinoma cells in vitro. J Dig Dis. 2014;15:684–93.

    CAS  Article  Google Scholar 

  35. 35.

    Liu H, Xu H-W, Zhang Y-Z, Huang Y, Han G-Q, Liang T-J, et al. Ursodeoxycholic acid induces apoptosis in hepatocellular carcinoma xenografts in mice. World J Gastroenterol. 2015;21:10367–74.

    CAS  Article  Google Scholar 

  36. 36.

    Gilbert JA, Blaser MJ, Caporaso JG, Jansson JK, Lynch SV, Knight R. Current understanding of the human microbiome. Nat Med. 2018;24:392–400.

    CAS  Article  Google Scholar 

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Correspondence to Shehnaz K. Hussain.

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Dong, T.S., Jacobs, J.P. & Hussain, S.K. Microbial Profiles of Cirrhosis in the Human Small Intestine. Curr Gastroenterol Rep 21, 50 (2019). https://doi.org/10.1007/s11894-019-0717-2

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Keywords

  • Microbiome
  • Bile acids
  • Cirrhosis
  • Hepatic encephalopathy
  • Portal hypertension
  • Ascites