Fecal Metabolic Dysbiosis Score: A Predictor of ICU Mortality Risk

In a groundbreaking study published in Science Advances on June 18, 2025, researchers at the University of Chicago have established that a fecal metabolic dysbiosis score (MDS) can predict 30-day mortality in critically ill patients admitted to the medical intensive care unit (MICU). The study, led by Dr. Alexander P. de Porto, analyzed fecal specimens from 196 patients, revealing that the MDS may serve as a novel biomarker to identify individuals at high risk of mortality, thereby potentially guiding targeted therapeutic strategies.

The research team prospectively collected fecal samples from patients suffering from non-COVID-19 respiratory failure or shock. The participants had a median age of 64 years, with a balanced representation of men and women. Through shotgun metagenomic sequencing, the researchers defined the microbiome compositions and quantified associated metabolites via mass spectrometry. This rigorous methodology allowed the team to correlate specific microbiota features and metabolites with 30-day mortality rates.

The findings indicated that the overall mortality rate within the cohort was 30.6%. Notably, the analysis showed no significant differences between survivors and nonsurvivors concerning age, sex, race, or comorbidity burden. While microbiota compositions of initial fecal samples did not independently correlate with mortality, the integration of 13 microbiota-derived metabolites led to the development of the MDS, which effectively predicted mortality independent of known confounders. This innovative score may enhance existing risk assessment tools by incorporating modifiable, microbiome-related factors that contribute to patient resilience.

Dr. de Porto emphasized the significance of their findings, stating, "Fecal metabolic dysbiosis, determined by quantification of 13 fecal metabolites, is independently associated with 30-day mortality after MICU admission in our cohort. Therefore, fecal metabolic dysbiosis represents a potentially treatable trait to improve survival in heterogeneous critically ill patients."

The implications of this research are profound, suggesting that interventions targeting gut microbiota may improve outcomes for critically ill patients. However, it is important to note the limitations of the study; the patient cohort was recruited from a single tertiary academic center, and the results may not be generalizable to the entire MICU population. Moreover, patients who did not produce analyzable fecal samples were excluded from the study, potentially biasing the results.

Funding for the study was provided by the Duchossois Family Institute and other institutions, including the National Institutes of Health (NIH). Dr. de Porto received support through the Niels Stensen Fellowship. The Center for Research Informatics at the University of Chicago also contributed to this research.

As the medical community continues to explore the relationship between the gut microbiome and critical illness, the MDS presents a promising avenue for improving patient outcomes. Future studies are needed to validate these findings across diverse populations and to assess the effectiveness of microbiome-targeted therapies in clinical practice.