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World J Hepatol. Sep 28, 2016; 8(27): 1128-1136
Published online Sep 28, 2016. doi: 10.4254/wjh.v8.i27.1128
Implication of the intestinal microbiome in complications of cirrhosis
Mamatha Bhat, Bianca M Arendt, Venkat Bhat, Eberhard L Renner, Atul Humar, Johane P Allard
Mamatha Bhat, Bianca M Arendt, Eberhard L Renner, Johane P Allard, Division of Gastroenterology, University Health Network, Toronto M5G 2N2, Canada
Mamatha Bhat, Eberhard L Renner, Atul Humar, Multi-organ Transplant Program, University Health Network, Toronto M5G 2N2, Canada
Mamatha Bhat, Eberhard L Renner, Atul Humar, Johane P Allard, Department of Medicine, University of Toronto, Toronto M5G 2N2, Canada
Venkat Bhat, Department of Psychiatry, McGill University, Montreal H3A 1A1, Canada
Author contributions: Bhat M performed the data collection, majority of the writing, prepared the figures and tables; Bhat V helped with data collection; Arendt BM, Renner EL, Humar A and Allard JP provided the input in writing the paper.
Conflict-of-interest statement: There is no conflict of interest associated with the senior author or other coauthors contributed their efforts in this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Mamatha Bhat, MD, Department of Medicine, University of Toronto, 585 University Avenue, Toronto M5G 2N2, Canada. mamatha.bhat@mail.mcgill.ca
Telephone: +1-416-3404800 Fax: +1-416-3404041
Received: March 18, 2016
Peer-review started: March 21, 2016
First decision: April 19, 2016
Revised: May 6, 2016
Accepted: July 29, 2016
Article in press: August 1, 2016
Published online: September 28, 2016
Abstract

The intestinal microbiome (IM) is altered in patients with cirrhosis, and emerging literature suggests that this impacts on the development of complications. The PubMed database was searched from January 2000 to May 2015 for studies and review articles on the composition, pathophysiologic effects and therapeutic modulation of the IM in cirrhosis. The following combination of relevant text words and MeSH terms were used, namely intestinal microbiome, microbiota, or dysbiosis, and cirrhosis, encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome, variceal bleeding, hepatopulmonary syndrome, portopulmonary hypertension and hepatocellular carcinoma. The search results were evaluated for pertinence to the subject of IM and cirrhosis, as well as for quality of study design. The IM in cirrhosis is characterized by a decreased proportion of Bacteroides and Lactobacilli, and an increased proportion of Enterobacteriaceae compared to healthy controls. Except for alcoholic cirrhosis, the composition of the IM in cirrhosis is not affected by the etiology of the liver disease. The percentage of Enterobacteriaceae increases with worsening liver disease severity and decompensation and is associated with bacteremia, spontaneous bacterial peritonitis and hepatic encephalopathy. Lactulose, rifaximin and Lactobacillus-containing probiotics have been shown to partially reverse the cirrhosis associated enteric dysbiosis, in conjunction with improvement in encephalopathy. The IM is altered in cirrhosis, and this may contribute to the development of complications associated with end-stage liver disease. Therapies such as lactulose, rifaximin and probiotics may, at least partially, reverse the cirrhosis-associated changes in the IM. This, in turn, may prevent or alleviate the severity of complications.

Keywords: Encephalopathy, Intestinal microbiome, Cirrhosis

Core tip: There has recently been an increasing understanding of the importance of the intestinal microbiome (IM) in the physiology of cirrhosis and its complications. Novel sequencing techniques have enabled a better characterization of the bacteria in the IM of patients with cirrhosis, and how this differs from the microbiome in a healthy individual. Additionally, therapeutics for enteric dysbiosis in patients with cirrhosis have been studied, and have shown promise in reducing the morbidity of complications in cirrhosis. In this review, we will critically review the literature on characterization of the IM in cirrhosis, its role in complications, and the evidence for strategies to address enteric dysbiosis.