IDENTIFICATION OF NOVEL INTESTINAL MICROBIOTA-BASED MARKERS ASSOCIATED WITH DYSBIOSIS, SEPSIS AND SHORT-TERM MORTALITY IN ALCOHOL-RELATED DECOMPENSATED CIRRHOSIS AND ACUTE-ON-CHRONIC LIVER FAILURE

Introduction and Objectives

Decompensated cirrhosis (DC) and acute-on-chronic liver failure (ACLF) related to alcohol present high morbidity and mortality and complications such as sepsis and multiorgan failure. The intestinal microbiota (IM) suffers from marked dysbiosis, altering SCFA biosynthesis and affecting the gut-liver axis. The microbial pathways involved, poorly understood in these pathologies, could represent useful prognostic markers.

To evaluate the relative quantification of bacterial SCFA genes in the IM of patients with CD and ACLF, and their association with different clinical outcomes and alpha-diversity.

Materials and Methods

Retrospective analytical study. Fecal samples from 19 ACLF patients, 16 DC, and 16 healthy controls (HC) were included. The butCoA, buk, ackA, and mmdA genes were quantified by qPCR. ROC curves and Kaplan-Meier analyses were performed using GraphPad. Approval number: CI-01023. No conflicts of interest are reported.

Results

Relative abundances of butCoA and ackA genes were significantly decreased in DC and ACLF patients (p<0.05), whereas mmdA increased in DC. buk increased in patients who died at 28 days (p<0.01) and showed a negative correlation with alpha-diversity, being associated with dysbiosis. Furthermore, buk and butCoA discriminated 28-day mortality in DC and ACLF (AUROC 0.75 and 0.85, respectively). In Kaplan-Meier analyses, increased buk was associated with 28-day mortality of 53% in DC and 71% in ACLF.

Conclusions

Intestinal microbiota of DC/ACLF showed reduction of butCoA, ackA, and mmdA, correlating with functional loss. Increased buk was associated with 28-day mortality, loss of alpha-diversity and sepsis. These findings propose novel microbial biomarkers in the Mexican population which will have to be validated later.

Conflict of interest: None

(A) Relative quantification of bacterial genes encoding SCFA biosynthesis-related genes in feces of the three study groups and (B) Kaplan-Meier mortality analysis on 28- and 90-day mortality in DC and ACLF patients, according to the Cq value cut-off point for the buk gene, established by ROC curves.