A six molecule nenonatal serum metabolite biosignature has high neonatal sepsis predictability and resolves upon treatment completion

Abstract

Sepsis, a life-threatening multi-organ dysfunction by a dysregulated host response, is one of the leading causes of mortality in neonates. Current microbiology-based sepsis diagnosis is time-consuming, and identifying serum metabolite markers may help develop early screening tools and host-directed therapeutics. A set of 131 neonates (age 41.2% female) were classified as culture-positive or negative sepsis cases (CP, CN) and controls (no sepsis: NS and healthy) based on microbial culture and mass spectrometry results. Most of the sepsis cases were due to Acinetobacter baumannii, and serum samples were collected at the time of presentation and at follow-up time points responding to the treatment. Serum samples were grouped as discovery (n=71) and validation (n=60) sets and analyzed using gas chromatography and mass spectrometry (GC-MS). A set of 882 metabolic features was identified, and molecules with a fold change>1.5, VIP score> 1.0, and t-test p-value<0.05 were identified as important molecules. Signatures of myo-inositol with phenylalanine and myo-inositol with 1,5-anhydrohexitol showed a predictive accuracy of 0.84 and 0.79, respectively, to differentiate CP and CN from HC. Interestingly, the longitudinally followed-up CP and CN sepsis patients completing therapeutic intervention showed a comparable abundance of myo-inositol and phenylalanine to the healthy control levels. These deregulated metabolites contributed by the perturbed metabolic pathways in the immune cells or affected multiple organs of sepsis patients. They could be further explored for their potential as diagnostic and therapeutic targets.