Serum metabolic signature differentiates neonatal sepsis from controls and resolves upon recovery.

Description

Sepsis, a life-threatening disorder with multi-organ dysfunction, is a leading cause of neonatal mortality. Current microbiology-based sepsis diagnosis is time-consuming, and identification of deregulated host serum metabolite signatures might be useful to develop early screening tools and host-directed therapeutics. In this multi-institutional study, 500 neonates (41%, female) were classified to culture-positive (CP) or negative sepsis (CN) cases and controls (no sepsis: NS, healthy control: HC) based on their microbial culture and mass spectrometry test results. The neonates were randomly grouped into two discovery sets (I:n=71; II:n=269), a validation set (n=60), and a longitudinally followed-up population (n=100). Serum samples of these neonates were processed and profiled using gas chromatography coupled to either quadrupole or time-of-flight mass spectrometry (GC-MS/-TOF-MS). Deregulated (log2¬case/control ≥±0.58, p<0.05) serum metabolites in sepsis cases were identified from the discovery sets and their predictive accuracy in the validation set was calculated using area under the receiving operator characteristic curve (AUC of ROC). The abundance of these deregulated metabolites was monitored in the longitudinally followed-up neonates (CP:n=29, CN:n=35, and NS:n=36) completing therapeutic intervention. Most of the CP cases were Klebsiella pneumoniae (28.6%) or Acinetobacter baumannii (20.6%) positive. Gestational age (CP: 30.9±1.9 weeks, CN: 30.9±1.8 weeks, HC: 32.3±1.3 weeks, NS: 31.6±1.5 weeks) and birthweight (CP: 1.4±0.3 kg, CN: 1.4±0.4 kg, HC: 1.7±0.3 kg, NS: 1.6±0.3 kg) were lower in sepsis neonates compared to controls. Out of 57 identified serum metabolites, a set of six (1,5-Anhydro-D-sorbitol-Lactic-acid-Malic-acid-Myo-inositol-Phenylalanine-Lysine) were identified as sepsis biosignature. The AUC of ROC of the biosignature to predict CP or CN from HC was 0.97 and from NS was 0.84 and 0.64, respectively. Myo-inositol, malic acid, and 1,5-anhydro-D-sorbitol revert to the HC levels in neonates completing therapeutic intervention. A serum metabolite signature showed a >97% predictive accuracy for sepsis and could further be explored for its diagnostic potential and host-directed therapeutics development.

Steps to reproduce

This data contains the peak area of each analyte as measured using ChromaTOF software. The data can be used to create PLSDA models and volcano plots using MetaboAnalyst 5.0 and box plots using Graphpad Prism 8.

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