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

Abstract：

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 ≤ 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 ≤ 0.05). Of these, pseudouridine increased monocyte expression of TNFα and IL1β 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.

journal_name

Intensive Care Med

journal_title

Intensive care medicine

authors

Seymour CW,Yende S,Scott MJ,Pribis J,Mohney RP,Bell LN,Chen YF,Zuckerbraun BS,Bigbee WL,Yealy DM,Weissfeld L,Kellum JA,Angus DC

doi

10.1007/s00134-013-2935-7

subject

Has Abstract

pub_date

2013-08-01 00:00:00

pages

1423-34

issue

eissn

0342-4642

issn

1432-1238

journal_volume

pub_type

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