Alterations of gut microbiome and effects of probiotic therapy in patients with liver cirrhosis: A systematic review and meta-analysis

Abstract

Alterations in the gut microbiome usually occur in liver cirrhosis. Gut microbiome dysregulation damages the liver and accelerates the development of liver fibrosis. Probiotic treatment has gradually become a major method for improving the prognosis of liver cirrhosis and reducing its complications. However, alterations in the gut microbiome have revealed different results, and the therapeutic effects of various probiotics are inconsistent. We searched the PubMed, Medline, EMBASE, ScienceDirect, and Cochrane databases up to August 2022 and conducted a systematic review and meta-analysis of 17 relevant studies. The counts of Enterobacter (standardized mean difference [SMD] -1.79, 95% confidence interval [CI]: -3.08 to -0.49) and Enterococcus (SMD -1.41, 95% CI: -2.26 to -0.55) increased significantly in patients with cirrhosis, while the counts of Lactobacillus (SMD 0.63, 95% CI: 0.12-1.15) and Bifidobacterium (SMD 0.44, 95% CI: 0.12-0.77) decreased significantly. Blood ammonia (weighted mean difference [WMD] 14.61, 95% CI: 7.84-21.37) and the incidence of hepatic encephalopathy (WMD 0.40, 95% CI: 0.27-0.61) were significantly decreased in the probiotic group. As for mortality (MD 0.75, 95% CI: 0.48-1.16) and the incidence of spontaneous bacterial peritonitis (WMD -0.02, 95% CI: -0.07 to 0.03), no significant differences were found between the probiotic and placebo groups. In summary, the gut microbiome in cirrhosis manifests as decreased counts of Lactobacillus and Bifidobacterium and increased counts of Enterobacter and Enterococcus. Targeted supplementation of probiotics in cirrhosis, including Lactobacillus combined with Bifidobacterium or Bifidobacterium alone, can reduce blood ammonia and the incidence of hepatic encephalopathy. The effect is similar to that of lactulose, but it has no obvious effect on mortality and spontaneous bacterial peritonitis.