Fecal metabolite profiling identifies critically ill patients with increased 30-day mortality
- Alexander P. de Porto
- Nicholas P. Dylla
- Matthew Stutz
- Huaiying Lin
- Maryam Khalid
- Michael W. Mullowney
- Jessica Little
- Amber Rose
- David Moran
- Mary McMillin
- Victoria Burgo
- Rita Smith
- Che Woodson
- Carolyn Metcalfe
- Ramanujam Ramaswamy
- Christopher Lehmann
- Matthew Odenwald
- Nadeem Bandealy
- Jack Zhao
- Marie Kim
- Emerald Adler
- Anitha Sundararajan
- Ashley Sidebottom
- John P. Kress
- Krysta S. Wolfe
- Eric G. Pamer
- Bhakti K. Patel
2025-06-11
Critically ill patients admitted to the medical intensive care unit (MICU) have reduced intestinal microbiota diversity and altered microbiome-associated metabolite concentrations. Metabolites produced by the gut microbiota have been associated with survival of patients receiving complex medical treatments and thus might represent a treatable trait to improve clinical outcomes. We prospectively collected fecal specimens, defined microbiome compositions by shotgun metagenomic sequencing, and quantified microbiota-derived fecal metabolites by mass spectrometry from 196 critically ill patients admitted to the MICU for non–COVID-19 respiratory failure or shock to correlate microbiota features and metabolites with 30-day mortality. Microbiota compositions of the first fecal sample after MICU admission did not independently associate with 30-day mortality. We developed a metabolic dysbiosis score (MDS) that uses fecal concentrations of 13 microbiota-derived metabolites, which predicted 30-day mortality independent of known confounders. The MDS complements existing tools to identify patients at high risk of mortality by incorporating potentially modifiable, microbiome-related, independent contributors to host resilience.