Related Experiment Video
Updated: Jan 23, 2026
Identification and Quantification of Deranged Metabolites in Critically Ill Patients Using NMR-Based Metabolomics
Published on: November 29, 2024
Multi-Compartment Profiling of Bacterial and Host Metabolites Identifies Intestinal Dysbiosis and Its Functional
Anisha Wijeyesekera1, Josef Wagner2, Marcus De Goffau1
1Department of Human Microbiome Studies, University of Reading, Berkshire, United Kingdom.
Objectives:
Adverse physiology and antibiotic exposure devastate the intestinal microbiome in critical illness. Time and cost implications limit the immediate clinical potential of microbial sequencing to identify or treat intestinal dysbiosis. Here, we examined whether metabolic profiling is a feasible method of monitoring intestinal dysbiosis in critically ill children.
Design:
Prospective multicenter cohort study.
Setting:
Three U.K.-based PICUs.
Patients:
Mechanically ventilated critically ill (n = 60) and age-matched healthy children (n = 55).
Interventions:
Collection of urine and fecal samples in children admitted to the PICU. A single fecal and urine sample was collected in healthy controls.
Measurements And Main Results:
Untargeted and targeted metabolic profiling using 1H-nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry or urine and fecal samples. This was integrated with analysis of fecal bacterial 16S ribosomal RNA profiles and clinical disease severity indicators. We observed separation of global urinary and fecal metabolic profiles in critically ill compared with healthy children. Urinary excretion of mammalian-microbial co-metabolites hippurate, 4-cresol sulphate, and formate were reduced in critical illness compared with healthy children. Reduced fecal excretion of short-chain fatty acids (including butyrate, propionate, and acetate) were observed in the patient cohort, demonstrating that these metabolites also distinguished between critical illness and health. Dysregulation of intestinal bile metabolism was evidenced by increased primary and reduced secondary fecal bile acid excretion. Fecal butyrate correlated with days free of intensive care at 30 days (r = 0.38; p = 0.03), while urinary formate correlated inversely with vasopressor requirement (r = -0.2; p = 0.037).
Conclusions:
Disruption to the functional activity of the intestinal microbiome may result in worsening organ failure in the critically ill child. Profiling of bacterial metabolites in fecal and urine samples may support identification and treatment of intestinal dysbiosis in critical illness.
Related Concept Videos
01:29Bacterial Flora of the Large Intestine
The normal gut flora of the colon plays a critical role in generating essential vitamins such as vitamins K, B5, and B7.
01:20Digestive Functions of the Large Intestine
As the chyme moves to the colon, it triggers two characteristic sluggish contractions - haustral churning and mass peristalsis. Haustral churning involves the rhythmic contraction and relaxation...
01:08Timing and Consequences on Behavior
Humans, however, can respond to delayed reinforcers. We often make decisions between immediate small rewards and delayed larger rewards. This ability to delay gratification is a significant...
01:20Compartment Models: Two-Compartment Model
01:23Anatomy of the Intestines
Small Intestines
The small intestine is an ~7 meter-long tube with an inner diameter of just 2.5 cm. Since most nutrients are absorbed here, the inner lining of the...
01:16Critical Region, Critical Values and Significance Level
In hypothesis testing, a sample statistic is converted to a test statistic using z, t, or chi-square distribution. A critical region is an area under the curve in probability distributions demarcated by the critical value. When the test statistic falls in this region, it suggests that the null hypothesis must be rejected. As this region contains all those values of the...