Fecal metabolite profiling identifies critically ill patients with increased 30-day mortality
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.
Authors
- Matthew A. Odenwald (ORCID: https://orcid.org/0000-0003-1740-6472)
- Michael W. Mullowney (ORCID: https://orcid.org/0000-0002-2884-4307)
- Anitha Sundararajan (ORCID: https://orcid.org/0000-0001-9550-3644)
- Mary McMillin
- Marie Kim (ORCID: https://orcid.org/0000-0002-3373-6618)
- Bhakti K. Patel (ORCID: https://orcid.org/0000-0002-6517-2175)
- Jessica Little (ORCID: https://orcid.org/0000-0002-8032-1378)
- K.S. Wolfe (ORCID: https://orcid.org/0000-0001-5565-3496)
- M.R. Stutz
- Amber R. Rose (ORCID: https://orcid.org/0000-0002-1388-0305)
- Eric G. Pamer (ORCID: https://orcid.org/0000-0002-6755-9904)
- Victoria Burgo (ORCID: https://orcid.org/0000-0003-1016-3199)
- Che Woodson
- Nicholas P. Dylla (ORCID: https://orcid.org/0000-0002-8731-5640)
- Alexander P. de Porto (ORCID: https://orcid.org/0000-0002-1201-0754)
- Christopher Lehmann (ORCID: https://orcid.org/0000-0002-1111-2169)
- Ashley M. Sidebottom (ORCID: https://orcid.org/0000-0002-8670-9090)
- Huaiying Lin (ORCID: https://orcid.org/0000-0003-2339-9491)
- Carolyn Metcalfe (ORCID: https://orcid.org/0000-0002-9304-8681)
- Rita C. Smith (ORCID: https://orcid.org/0000-0002-7546-5019)
- J.P. Kress
- Ramanujam Ramaswamy (ORCID: https://orcid.org/0000-0001-7448-6574)
- D.M. Moran (ORCID: https://orcid.org/0009-0001-8537-8269)
- Nadeem Bandealy
- Maryam Khalid
- Jiong Zhao (ORCID: https://orcid.org/0000-0003-1124-6455)
- Emerald Adler
Institutions
- Northern Illinois University (US)
- Chicago Department of Public Health (US)
- Purdue University West Lafayette (US)
- John H. Stroger, Jr. Hospital of Cook County (US)
- University of Illinois Chicago (US)
- University of Chicago (US)
- New York Institute of Technology (US)
- Ecolab (United States) (US)
- Tempus Labs (United States) (US)
- Amsterdam University of Applied Sciences (NL)
- University of Amsterdam (NL)
Publication Details
- Journal
- Science Advances
- Published
- 2025-06-06
- DOI
- https://doi.org/10.1126/sciadv.adt1466
- Citations
- 3
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 2.42