# Deciphering the Language of Intestinal Microbiota Associated with Sepsis, Organ Failure, and Mortality in Patients with Alcohol-Related Acute-on-Chronic Liver Failure (ACLF): A Pioneer Study in Latin America

## TL;DR

This study explores how gut bacteria in patients with alcohol-related liver failure in Latin America are linked to sepsis, organ failure, and mortality.

## Contribution

The study is the first to investigate intestinal microbiota in ACLF patients in Latin America and identifies potential biomarkers for mortality and sepsis.

## Key findings

- Patients with ACLF showed significant changes in gut microbiota diversity compared to healthy controls.
- The Klebsiella/Faecalibacterium ratio effectively predicted sepsis, and certain bacteria were linked to mortality and multiorgan failure.
- Higher levels of Proteobacteria and LPS correlated with disease severity and organ dysfunction.

## Abstract

ACLF is a severe stage of liver cirrhosis, characterized by multiple organ failure, systemic inflammation, and high short-term mortality. The intestinal microbiota (IM) influences its pathophysiology; however, there are currently no studies in Latin American populations. Therefore, we analyzed IM and its relationships with sepsis, organ failure, and mortality. In parallel, we quantified serum lipopolysaccharides as a marker of bacterial translocation. Fecal samples from 33 patients and 20 healthy controls (HCs) were obtained. The IMs were characterized by 16S-rRNA amplicon sequencing, the metagenomic functional predictive profiles were analyzed by PICRUSt2, and LPS quantification was performed by ELISA. Patients with ACLF showed significant alterations in alpha and beta diversity compared to the HCs. A strong dominance index accurately predicted 28-day and 90-day mortalities. The IMs showed a polarization toward Proteobacteria associated with increased LPS. The LPS correlated with clinical severity, organ dysfunction, and higher pathogenic taxa. The Klebsiella/Faecalibacterium ratio showed good performance in identifying sepsis (AUROC = 0.83). Furthermore, Morganella, Proteus, and Klebsiella were enriched in patients with multiorgan failure. Lactobacillus, Escherichia/Shigella, Veillonella, and Ruminococcus gnavus exhibited potential in predicting 28- and 90-day mortalities. The IM alterations in ACLF may be useful as clinical biomarkers of poor prognosis, primarily for mortality and sepsis. These findings are representative of western Mexico.