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.

Microbiome and bile acid profiles in duodenal aspirates from patients with liver cirrhosis: The Microbiome, Microbial Markers and Liver Disease Study

“…Although prior studies have shown that small intestinal bacterial overgrowth is associated with HE, we additionally found that patients with HE also have lower microbial richness and diversity in the duodenum compared to patients without HE . Potentially related to this observation are prior reports that have linked lower diversity of the fecal microbiome to cirrhosis severity . Lactulose, a non‐absorbable sugar, and rifaximin, a minimally absorbed antibiotic, are typically used as first‐line treatments for HE and were used by 7 and 10 participants in our study, respectively.…”

Role of Gut Dysbiosis in Liver Diseases: What Have We Learned So Far?

“…Bacterial DNA was reported to be detected in blood and ascites in one-third of cirrhotic patients with portal hypertension and culture-negative ascites [209]. Most bacteria causing SBP are Gram-negative bacilli, especially Enterobacteriaceae family (E. coli, Enterobacter, Klebsiella and Proteus), which are predominant in the gut microbiota of cirrhotic patients [38,184,188,210,211]. Bajaj et al [40] found that fecal microbiota in cirrhotic patients admitted with infections showed significant differences in the fecal microbiota characterized by increased Enterobacteriaceae and decreased Coriobacteriaceae, Lachnospiraceae, Ruminococcaceae, Veillonellaceae and Clostridiales XIV, lower CDR and higher plasma endotoxin levels compared with those without infections.…”

Unique subgingival microbiota associated with periodontitis in cirrhosis patients

“…Another factor that might disturb the microbiome in liver cirrhosis patients is lactulose, which is used as a prebiotic for patients with liver cirrhosis and hepatic encephalopathy 52 – 54 . Lactulose acidifies the colonic pH, which renders the environment hostile to the urease-producing Klebsiella and Proteus species, while promoting non-urease-producing and aciduric lactobacilli and bifidobacteria 55 . In the few studies that have investigated the direct effect of lactulose on the gut microbiome in liver cirrhosis patients no major changes of the gut microbiome composition were found 56 , 57 .…”

“…It is well established that liver cirrhosis patients become immunocompromised, which is responsible for many of the complications observed, including bacterial infections 66 , 67 . The changes in the gut microbiota in liver cirrhosis patients have been proposed to be caused by a combination of the direct effect of the liver on the gut as well as by their immunocompromised status 22 , 24 , 55 . Recent studies showed that the oral microbiome associated with periodontitis differs greatly between HIV positive and HIV negative patients 46 , 68 , 69 .…”