Published June 4, 2025 | Version v1
Journal article Open

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

Description

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.

Data availability

Metabolomics data is available at https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=24a010b7e6a34ac88cd45b3848c88cc0. Metagenomics sequencing data is available at https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1134172. The code used in this paper is available at https://zenodo.org/records/14968628. All other data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.

Files

sciadv.adt1466.pdf

Files (2.3 MB)

Name Size Download all
Article
md5:634df3c9527a79ca9417599fb28fe881
1.8 MB Preview Download
Supplementary Materials
md5:9c315be79d38aaf853e58bcd6683404e
541.0 kB Preview Download

Additional details

Identifiers

DOI
10.1126/sciadv.adt1466
Other
oai:uchicago.tind.io:15462

Funding

National Institutes of Health
UL1 TR000430
National Heart, Lung, and Blood Institute
K23 HL148387
Unknown funder
Niels Stensen Fellowship
University of Chicago

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Medicine
Center(s) or Institute(s)
Duchossois Family Institute