Changes in the Microbiome in Cirrhosis and Relationship to Complications: Hepatic Encephalopathy, Spontaneous Bacterial Peritonitis, and Sepsis

Abstract

Chronic liver disease with progression to decompensated cirrhosis and its associated complications, including hepatic encephalopathy, spontaneous bacterial peritonitis, and sepsis, is a leading cause of mortality and morbidity. The pathophysiology of decompensated cirrhosis, which is being intensively studied, leads to the development of gut microbiome changes causing dysbiosis. This is likely related to altered bile acid composition, with a subsequent increase in the relative abundance of potentially pathogenic bacteria that contributes to hepatic encephalopathy and leads to their translocation and the development of spontaneous bacterial peritonitis and bacteremia. Treatments for these conditions have been found to target the gut microbiome, which has become a vital area of study in the treatment of cirrhosis.

Keywords

hepatic encephalopathy - rifaximin - lactulose - infection - cirrhosis dysbiosis ratio

• References

• 1 Peery AF, Crockett SD, Barritt AS , et al. Burden of gastrointestinal, liver, and pancreatic diseases in the United States. Gastroenterology 2015; 149 (7) 1731-1741 .e3
• 2 Schnabl B, Brenner DA. Interactions between the intestinal microbiome and liver diseases. Gastroenterology 2014; 146 (6) 1513-1524
• 3 Khanna S, Tosh PK. A clinician's primer on the role of the microbiome in human health and disease. Mayo Clin Proc 2014; 89 (1) 107-114
• 4 Karlsson F, Tremaroli V, Nielsen J, Bäckhed F. Assessing the human gut microbiota in metabolic diseases. Diabetes 2013; 62 (10) 3341-3349
• 5 Bajaj JS. The role of microbiota in hepatic encephalopathy. Gut Microbes 2014; 5 (3) 397-403
• 6 Ridlon JM, Alves JM, Hylemon PB, Bajaj JS. Cirrhosis, bile acids and gut microbiota: unraveling a complex relationship. Gut Microbes 2013; 4 (5) 382-387
• 7 Kakiyama G, Pandak WM, Gillevet PM , et al. Modulation of the fecal bile acid profile by gut microbiota in cirrhosis. J Hepatol 2013; 58 (5) 949-955
• 8 Liu Q, Duan ZP, Ha DK, Bengmark S, Kurtovic J, Riordan SM. Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis. Hepatology 2004; 39 (5) 1441-1449
• 9 Gómez-Hurtado I, Such J, Sanz Y, Francés R. Gut microbiota-related complications in cirrhosis. World J Gastroenterol 2014; 20 (42) 15624-15631
• 10 Shawcross D, Jalan R. The pathophysiologic basis of hepatic encephalopathy: central role for ammonia and inflammation. Cell Mol Life Sci 2005; 62 (19-20) 2295-2304
• 11 Bajaj JS, Hylemon PB, Ridlon JM , et al. Colonic mucosal microbiome differs from stool microbiome in cirrhosis and hepatic encephalopathy and is linked to cognition and inflammation. Am J Physiol Gastrointest Liver Physiol 2012; 303 (6) G675-G685
• 12 Bajaj JS, Betrapally NS, Gillevet PM. Decompensated cirrhosis and microbiome interpretation. Nature 2015; 525 (7569) E1-E2
• 13 Bajaj JS, Betrapally NS, Hylemon PB , et al. Salivary microbiota reflects changes in gut microbiota in cirrhosis with hepatic encephalopathy. Hepatology 2015; 62 (4) 1260-1271
• 14 Santiago A, Pozuelo M, Poca M , et al. Alteration of the serum microbiome composition in cirrhotic patients with ascites. Sci Rep 2016; 6: 25001
• 15 Vilstrup H, Amodio P, Bajaj J , et al. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology 2014; 60 (2) 715-735
• 16 Bajaj JS, Saeian K, Schubert CM , et al. Minimal hepatic encephalopathy is associated with motor vehicle crashes: the reality beyond the driving test. Hepatology 2009; 50 (4) 1175-1183
• 17 Patidar KR, Thacker LR, Wade JB , et al. Covert hepatic encephalopathy is independently associated with poor survival and increased risk of hospitalization. Am J Gastroenterol 2014; 109 (11) 1757-1763
• 18 Riordan SM, Williams R. Gut flora and hepatic encephalopathy in patients with cirrhosis. N Engl J Med 2010; 362 (12) 1140-1142
• 19 Rai R, Saraswat VA, Dhiman RK. Gut microbiota: its role in hepatic encephalopathy. J Clin Exp Hepatol 2015; 5 (Suppl. 01) S29-S36
• 20 Kang DJ, Betrapally NS, Ghosh SA , et al. Gut microbiota drive the development of neuroinflammatory response in cirrhosis in mice. Hepatology 2016; 64 (4) 1232-1248
• 21 Ahluwalia V, Betrapally NS, Hylemon PB , et al. Impaired gut-liver-brain axis in patients with cirrhosis. Sci Rep 2016; 6: 26800
• 22 Bajaj JS, Heuman DM, Hylemon PB , et al. Altered profile of human gut microbiome is associated with cirrhosis and its complications. J Hepatol 2014; 60 (5) 940-947
• 23 Wiest R, Lawson M, Geuking M. Pathological bacterial translocation in liver cirrhosis. J Hepatol 2014; 60 (1) 197-209
• 24 Tuomisto S, Pessi T, Collin P, Vuento R, Aittoniemi J, Karhunen PJ. Changes in gut bacterial populations and their translocation into liver and ascites in alcoholic liver cirrhotics. BMC Gastroenterol 2014; 14: 40-230X
• 25 Kakiyama G, Hylemon PB, Zhou H , et al. Colonic inflammation and secondary bile acids in alcoholic cirrhosis. Am J Physiol Gastrointest Liver Physiol 2014; 306 (11) G929-G937
• 26 Bajaj JS, Cox IJ, Betrapally NS , et al. Systems biology analysis of omeprazole therapy in cirrhosis demonstrates significant shifts in gut microbiota composition and function. Am J Physiol Gastrointest Liver Physiol 2014; 307 (10) G951-G957
• 27 Freedberg DE, Lebwohl B, Abrams JA. The impact of proton pump inhibitors on the human gastrointestinal microbiome. Clin Lab Med 2014; 34 (4) 771-785
• 28 Chen Y, Guo J, Qian G , et al. Gut dysbiosis in acute-on-chronic liver failure and its predictive value for mortality. J Gastroenterol Hepatol 2015; 30 (9) 1429-1437
• 29 Bajaj JS, Betrapally NS, Hylemon PB , et al. Gut microbiota alterations can predict hospitalizations in cirrhosis independent of diabetes mellitus. Sci Rep 2015; 5: 18559