The contents of a patient’s entrails could be key to assessing how close they are to death, according a team of doctors who created an index of markers in a patient’s faeces that can help gauge the risk of mortality within 30 days.
Led by Alexander de Porto of the University of Chicago and the University of Amsterdam, they have named it the metabolic dysbiosis score (MDS), and suggest it could help save the lives of critically ill patients in medical intensive care.
Their results, they caution, require further investigation and validation, but offer exciting promise as a future tool for diagnostic medicine.
“The findings suggest that faecal metabolic dysbiosis, quantified through the MDS, holds potential as a biomarker to identify critically ill patients at increased risk of mortality,” said De Porto and his colleagues, Eric Pamer and Bhakti Patel of the University of Chicago.
“This underscores the importance of gut-derived metabolites as independent contributors to host resilience, offering an avenue for precision medicine.”
Critically ill patients admitted to intensive care units often develop severe syndromes like sepsis and acute respiratory distress, but these syndromes don’t always develop and evolve in the same way. This heterogeneity poses a huge challenge for trying to treat these patients; two patients with the same syndrome may respond to the same treatment very differently.
One way to circumvent this challenge, the researchers said, is to identify specific traits to treat rather than attacking the whole syndrome at once. Scientists know that critically ill patients often have reduced diversity in their gut microbiota, as well as altered concentrations of the metabolites produced by their microbiomes.
De Porto and his colleagues embarked on an investigation into dysbiosis, an imbalance in the gut microbiome, in critically ill patients, as a trait that could be treated.
They studied faecal samples collected from 196 patients exhibiting respiratory failure or shock, dividing them into a training cohort of 147 patients and a validation cohort of 49 patients.
They used these samples to develop the MDS, based on concentrations of 13 distinct faecal metabolites. The results indicate an auspicious avenue for further investigation.
“The MDS performed well in predicting mortality in the training cohort of medical ICU patients, with 84% accuracy, 89% sensitivity, and 71% specificity,” the researchers said.
“However, the validation cohort, despite showing similar trends, failed to reach statistical significance, probably due to its smaller sample size. These findings highlight the promise of the MDS but also underscore the necessity to validate its predictive capacity and generalisability in independent cohorts before widespread application.”
What the researchers found particularly interesting is that, even though a lack of diversity in the microbiome has previously been associated with adverse outcomes in critically ill patients, they could find no such link. Instead, their results showed a strong link between dysbiosis and increased mortality risk, suggesting that an imbalance in the microbiome plays a crucial role in patient health.
A lot more work needs to be done before the team’s approach is suitable for clinical application. The null result in the validation cohort of just 47 patients shows that quite a bit of refinement is required. However, there are several encouraging points.
The lab has shown, for instance, that faecal metabolites can identify liver transplant patients who have a higher risk of developing a post-operative infection. In addition, while specific treatments have not yet been investigated or identified, the MDS indicates some pathways for further exploration.
“The metabolites comprising the score, such as short-chain fatty acids, bile acids, and tryptophan metabolites, point to biological pathways that might be targeted therapeutically,” the researchers said. “Potential interventions might include dietary changes, administration of probiotics, or direct supplementation with these metabolites.”
The next step is to work on validating MDS in new sets of patients, and to examine whether the link between the observed dysbioses and the increased mortality risk is causal or symptomatic of another cause.
“Subsequently,” the researchers said, “intervention trials targeting specific metabolites or metabolic pathways are necessary to assess therapeutic benefits.”
The research was published in Science Advances.
Study details
Faecal metabolite profiling identifies critically ill patients with increased 30-day mortality
Alexander De Porto, Nicholas Dylla, Matthew Stutz et al.
Published in Science Advances on 4 June 2025
Abstract
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 faecal specimens, defined microbiome compositions by shotgun metagenomic sequencing, and quantified microbiota-derived faecal 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 faecal sample after MICU admission did not independently associate with 30-day mortality. We developed a metabolic dysbiosis score (MDS) that uses faecal 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.
See more from MedicalBrief archives:
Microbiome patterns predict colorectal cancer occurrence
Metabolites identified that may help predict ME/CFS