A Systematic Review of Microbiota in Cirrhosis: A Change Towards a More Pathogenic Predisposition

Abstract

The microbiome of the human intestine is a regulator of health that modulates immune response and plays an important role in metabolism. The diversity, and abundance of microbiota communities in the gut have been shown to change in cirrhosis and its complications. We aimed to review the current knowledge regarding microbiota alterations in cirrhosis, its potential differences according to etiology, and its role in the development of cirrhosis complications. A systematic search of the online bibliographic database up to July 2024 was performed. Randomized controlled trials and observational and cohort studies that included a total or at least a cohort of cirrhotic adult patients were enlisted for data extraction and analysis. A total of 73 publications were included for data extraction. Alpha diversity was found to decrease in cirrhotic patients in 30/38 (78%) of the studies, while beta diversity in 20/22 (90%) presented significant differences between healthy and cirrhotic groups. Proteobacteria significantly increased in 20/27 (74%) studies, followed by Actinobacteria and Fusobacteria, while 22/25 (88%) studies found either a reduction in cirrhotic patients or increased abundance in healthy controls for Firmicutes and Bacteroidetes. The most abundant genera in hepatic encephalopathy groups were pathobionts such as Enterococcus and Streptococcus, followed by Vellionella and Escherichia. Heterogeneity was found among studies regarding Alpha diversity in hepatocellular carcinoma (HCC) as it was decreased in three studies, indifferent in five, and increased in three studies in comparison to cirrhotic non-HCC patients. The dysbiosis of the gut microbiota is associated with cirrhosis and the development of complications such as hepatic encephalopathy and hepatocellular carcinoma.

Keywords: bacterial overgrowth; cirrhosis; dysbiosis; hepatic encephalopathy; hepatocellular carcinoma; microbiota.

Figure 1

PRISMA flowchart of excluded and included studies for microbiota changes in cirrhosis.

Figure 2

Patients included in the study and their relative groups of etiology according to geographical distribution.

Figure 3

Results from studies reporting alpha and beta diversities of gut microbiota differences in liver cirrhosis (LC) patients vs. healthy controls (HC), cirrhotic patients with vs. without hepatic encephalopathy (HE), cirrhotic patients with vs. without hepatocellular cancer (HCC), and cirrhotic patients with vs. without decompensation.

Figure 4

Gut microbiota enriched in liver cirrhosis. (The number of studies that support enrichment/the number of studies that support reduction). * Although the abundance of firmicutes is reduced in patients with liver cirrhosis compared to healthy subjects, some families and genera included in this phylum tend to be significantly enriched.

Figure 5

Gut microbiota decreased in liver cirrhosis vs. healthy subjects. (The number of studies that support reduction/the number of studies that support enrichment). * Although the abundance of Actinobacteria is increased in patients with liver cirrhosis compared to healthy subjects, Bifidobacterium tends to be more enriched in healthy vs. cirrhotic patients.

Figure 6

Comparison of hepatic encephalopathy and hepatocellular carcinoma as the most presented bacteria taxon in the studies. (The number of studies that show an increase/the number of studies that show no increase or decrease). Taxa that are reported in the results of at least two or more studies are presented in the graph.