Fecal Metabolite Profiling Predicts Mortality in Critically Ill Patients

Image: Critically ill patients have reduced intestinal microbiota diversity and altered microbiome-associated metabolite concentrations (Photo courtesy of 123RF)

Critically ill patients in medical intensive care units (MICUs) often suffer from conditions such as acute respiratory distress syndrome (ARDS) or sepsis, which are linked to reduced diversity of gut microbiota and altered concentrations of microbiome-related metabolites. These metabolites have been associated with patient survival and could represent modifiable factors to improve outcomes. Now, researchers have developed a novel diagnostic tool—a metabolic dysbiosis score (MDS)—based on fecal metabolite profiling that can identify critically ill patients at higher risk of 30-day mortality.

The study, conducted by researchers at the University of Chicago (Chicago, IL, USA), aimed to uncover gut microbiome characteristics and metabolic signatures associated with mortality in patients admitted to the MICU for non–COVID–19 respiratory failure or shock. To develop the tool, the researchers performed a prospective observational cohort study involving 196 critically ill patients. Fecal specimens were collected shortly after ICU admission and analyzed using shotgun metagenomic sequencing to define microbiome composition, along with mass spectrometry to quantify microbiota-derived metabolites. The findings, published in Science Advances, show that individual metabolite levels and microbial compositions in the initial samples did not correlate directly with 30-day mortality

However, a specific combination of metabolite concentrations led to the creation of the MDS from fecal concentrations of 13 specific metabolites found in the first fecal sample after ICU admission. It showed a statistically significant independent association with 30-day mortality, offering a metabolic snapshot that could help clinicians identify patients at greater risk of poor outcomes. Importantly, this approach highlights the functional activity of the microbiome, beyond just taxonomic profiling. The MDS offers a new, non-invasive method to stratify critically ill patients based on their likelihood of survival. It opens the door for targeted interventions, such as microbiome-augmentation strategies, by identifying patients who might benefit most. The researchers suggest that fecal metabolic profiling could guide future clinical trials focused on improving outcomes through modulation of the gut microbiota.