Implication of the intestinal microbiome in complications of cirrhosis

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.