Gut microbiota as prognosis markers for patients with HBV-related acute-on-chronic liver failure

Abstract

The gut microbiota in the hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is poorly defined. We aim to uncover the characteristics of the gut microbiota in HBV-ACLF and in other HBV associated pathologies. We analyzed the gut microbiome in patients with HBV-ACLF or other HBV associated pathologies and healthy individuals by 16S rRNA sequencing and metagenomic sequencing of fecal samples. 212 patients with HBV-ACLF, 252 with chronic hepatitis B (CHB), 162 with HBV-associated cirrhosis (HBV-LC) and 877 healthy individuals were recruited for the study. CHB and HBV-LC patients are grouped as HBV-Other. We discovered striking differences in the microbiome diversity between the HBV-ACLF, HBV-Other and healthy groups using 16S rRNA sequencing. The ratio of cocci to bacilli was significantly elevated in the HBV-ACLF group compared with healthy group. Further analysis within the HBV-ACLF group identified 52 genera showing distinct richness within the group where <i>Enterococcus</i> was enriched in the progression group whilst <i>Faecalibacterium</i> was enriched in the regression group. Metagenomic sequencing validated these findings and further uncovered an enrichment of <i>Lactobacillus casei paracasei</i> in progression group, while <i>Alistipes senegalensis, Faecalibacterium prausnitzii</i> and <i>Parabacteroides merdae</i> dominated the regression group. Importantly, our analysis revealed that there was a rapid increase of <i>Enterococcus faecium</i> during the progression of HBV-ACLF. The gut microbiota displayed distinct composition at different phases of HBV-ACLF. High abundance of <i>Enterococcus</i> is associated with progression while that of <i>Faecalibacterium</i> is associated with regression of HBV-ACLF. Therefore, the microbiota features hold promising potential as prognostic markers for HBV-ACLF.