Comprehensive Strain-Level Analysis of the Gut Microbe Faecalibacterium prausnitzii in Patients with Liver Cirrhosis

Abstract

ABSTRACT Liver cirrhosis (LC) has been associated with gut microbes. However, the strain diversity of species and its association with LC have received little attention. Here, we constructed a computational framework to study the strain heterogeneity in the gut microbiome of patients with LC. Only Faecalibacterium prausnitzii shows different single-nucleotide polymorphism (SNP) patterns between the LC and healthy control (HC) groups. Strain diversity analysis discovered that although most F. prausnitzii genomes are more deficient in the LC group than in the HC group at the strain level, a subgroup of 19 F. prausnitzii strains showed no sensitivity to LC, which is inconsistent with the species-level result. The functional differences between this subgroup and other strains may involve short-chain fatty acid production and chlorine-related pathways. These findings demonstrate functional differences among F. prausnitzii subgroups, which extend current knowledge about strain heterogeneity and relationships between F. prausnitzii and LC at the strain level. IMPORTANCE Most metagenomic studies focus on microbes at the species level, thus ignoring the different effects of different strains of the same species on the host. In this study, we explored the different microbes at the strain level in the intestines of patients with liver cirrhosis and of healthy people. Previous studies have shown that the species Faecalibacterium prausnitzii has a lower abundance in patients with liver cirrhosis than in healthy people. However, our results found multiple F. prausnitzii strains that do not decrease in abundance in patients with liver cirrhosis. It is more sensitive to select the appropriate strains as indicators to distinguish between the disease and the control samples than to use the entire species as an indicator. We clustered multiple F. prausnitzii strains and discuss the functional differences of different clusters. Our findings suggest that more attention should be paid to metagenomic studies at the strain level.

Keywords

• liver cirrhosis
• Faecalibacterium prausnitzii
• within-species variation
• species heterogeneity
• strain diversity
• strain-level analysis