Fecal Butyrate and Deoxycholic Acid Concentrations Correlate With Mortality in Patients With Liver Disease.

BACKGROUND AND AIMS

The intestinal microbiome produces metabolites, including short chain fatty acids (SCFAs) and secondary bile acids (BAs), that impact host physiology. Loss of intestinal microbiome diversity is associated with cirrhosis progression, but the impact of microbiome-associated metabolites on liver disease remains largely undefined. We aimed to correlate fecal metabolite concentrations with the severity and progression of liver disease.

METHODS

In this cross-sectional study, fecal samples from patients hospitalized with liver disease were analyzed by shotgun metagenomic sequencing to determine microbiome compositions and targeted mass spectrometry to quantify SCFAs and BAs. Random survival forest and logistic regression models identified clinical, metagenomic, and metabolomic features associated with rehospitalization and survival.

RESULTS

This cross-sectional study included 24 chronic liver disease, 18 compensated cirrhosis, 225 decompensated cirrhosis and 40 acute-on-chronic liver failure patients and 27 control fecal donors. Microbiome sequencing and metabolite profiling correlated microbial diversity and SCFA and BA concentrations with liver disease severity. Butyrate and deoxycholic acid (DCA) were more important features than individual microbial species in random survival forest models predicting 30-day transplant-free survival, and low butyrate and DCA were associated with 30-day mortality ( < .0001). After controlling for model for end stage liver disease (MELD)-sodium score, disease stage, age and gender, low fecal concentrations of butyrate and DCA remained significant risk factors for death (Cox 1.38, = .027). Bacterial species associated with butyrate and DCA concentrations included and .

CONCLUSION

Mass spectrometry rapidly identifies patients with low fecal butyrate and DCA concentrations who are at increased risk of 30-day mortality. These findings set the stage for clinical trials of microbiome reconstitution with butyrate and DCA-producing bacterial species.