Metabolomics in pneumonia and sepsis: an analysis of the GenIMS cohort study

• Published in: Intensive Care Medicine 2013, Vol.39 (8), p.1423
• Main Authors: Seymour, Christopher W, Yende, Sachin, Scott, Melanie J, Pribis, John, Mohney, Robert P, Bell, Lauren N, Chen, Yi-Fan
• Format: Report
• Language: English
• Subjects: Analysis; Bacterial pneumonia; Bile acids; Cytokines; Health aspects; Liver; Medical research; Medicine, Experimental; Metabolites; Pneumonia
• ISSN: 0342-4642
• DOI: 10.1007/s00134-013-2935-7

Purpose To determine the global metabolomic profile as measured in circulating plasma from surviving and non-surviving patients with community-acquired pneumonia (CAP) and sepsis. Methods Random, outcome-stratified case-control sample from a prospective study of 1,895 patients hospitalized with CAP and sepsis. Cases (n = 15) were adults who died before 90 days, and controls (n = 15) were adults who survived, matched on demographics, infection type, and procalcitonin. We determined the global metabolomic profile in the first emergency department blood sample using non-targeted mass-spectrometry. We derived metabolite-based prognostic models for 90-day mortality. We determined if metabolites stimulated cytokine production by differentiated Thp1 monocytes in vitro, and validated metabolite profiles in mouse liver and kidney homogenates at 8 h in cecal ligation and puncture (CLP) sepsis. Results We identified 423 small molecules, of which the relative levels of 70 (17 %) were different between survivors and non-survivors (p [less than or equal to] 0.05). Broad differences were present in pathways of oxidative stress, bile acid metabolism, and stress response. Metabolite-based prognostic models for 90-day survival performed modestly (AUC = 0.67, 95 % CI 0.48, 0.81). Five nucleic acid metabolites were greater in non-survivors (p [less than or equal to] 0.05). Of these, pseudouridine increased monocyte expression of TNF[alpha] and IL1[beta] versus control (p < 0.05). Pseudouridine was also increased in liver and kidney homogenates from CLP mice versus sham (p < 0.05 for both). Conclusions Although replication is required, we show the global metabolomic profile in plasma broadly differs between survivors and non-survivors of CAP and sepsis. Metabolite-based prognostic models had modest performance, though metabolites of oxidative stress may act as putative damage-associated molecular patterns.