Fecal metabolite profiling identifies critically ill patients with increased 30-day mortality

Area of Science:

• Microbiology
• Metabolomics
• Critical Care Medicine

Background:

• Critically ill patients in the medical intensive care unit (MICU) exhibit reduced intestinal microbiota diversity and altered metabolite concentrations.
• Gut microbiota metabolites are linked to patient survival during complex medical treatments, suggesting they could be a targetable trait for improving outcomes.

Purpose of the Study:

• To investigate the correlation between gut microbiota composition, fecal metabolites, and 30-day mortality in critically ill patients.
• To develop and validate a predictive score for mortality based on microbiota-derived metabolites.

Main Methods:

• Prospective collection of fecal specimens from 196 critically ill patients (non-COVID-19 respiratory failure or shock).
• Shotgun metagenomic sequencing to define microbiome composition.
• Mass spectrometry to quantify fecal concentrations of microbiota-derived metabolites.
• Development of a metabolic dysbiosis score (MDS) based on 13 key metabolites.

Main Results:

• Microbiota composition alone did not independently predict 30-day mortality.
• The developed metabolic dysbiosis score (MDS) independently predicted 30-day mortality, even after accounting for known confounders.
• The MDS incorporates potentially modifiable, microbiome-related factors contributing to host resilience.

Conclusions:

• A metabolic dysbiosis score (MDS) derived from fecal metabolites can identify critically ill patients at higher risk of 30-day mortality.
• The MDS offers a novel, complementary tool for risk stratification in the MICU, highlighting the role of the gut microbiome in patient outcomes.