Functional gene arrays-based analysis of fecal microbiomes in patients with liver cirrhosis.

BACKGROUND: Human gut microbiota plays an important role in the pathogenesis of cirrhosis complications. Although the phylogenetic diversity of intestinal microbiota in patients with liver cirrhosis has been examined in several studies, little is known about their functional composition and structure.

RESULTS: To characterize the functional gene diversity of the gut microbiome in cirrhotic patients, we recruited a total of 42 individuals, 12 alcoholic cirrhosis patients, 18 hepatitis B virus (HBV)-related cirrhosis patients, and 12 normal controls. We determined the functional structure of these samples using a specific functional gene array, which is a combination of GeoChip for monitoring biogeochemical processes and HuMiChip specifically designed for analyzing human microbiomes. Our experimental data showed that the microbial community functional composition and structure were dramatically distinctive in the alcoholic cirrhosis. Various microbial functional genes involved in organic remediation, stress response, antibiotic resistance, metal resistance, and virulence were highly enriched in the alcoholic cirrhosis group compared to the control group and HBV-related cirrhosis group. Cirrhosis may have distinct influences on metabolic potential of fecal microbial communities. The abundance of functional genes relevant to nutrient metabolism, including amino acid metabolism, lipid metabolism, nucleotide metabolism, and isoprenoid biosynthesis, were significantly decreased in both alcoholic cirrhosis group and HBV-related cirrhosis group. Significant correlations were observed between functional gene abundances and Child-Pugh scores, such as those encoding aspartate-ammonia ligase, transaldolase, adenylosuccinate synthetase and IMP dehydrogenase.

CONCLUSIONS: Functional gene array was utilized to study the gut microbiome in alcoholic and HBV-related cirrhosis patients and controls in this study. Our array data indicated that the functional composition of fecal microbiomes was heavily influenced by cirrhosis, especially by alcoholic cirrhosis. This study provides new insights into the functional potentials and activity of gut microbiota in cirrhotic patients with different etiologies.