Application of integrated multi-omics analysis in identifying biomarkers for early diagnosis of neonatal necrotizing enterocolitis

Background This study aims to investigate the potential application and value of metabolomics combined with proteomics in identifying early biomarkers for neonatal necrotizing enterocolitis (NEC), to provide new perspectives and strategies for early diagnosis. Method A systematic comparison was conducted between two sample groups: a case group consisting of 8 preterm infants diagnosed with NEC and a control group of 8 healthy, age- and weight-matched neonates without NEC. To capture metabolic changes at the onset of NEC, blood samples were collected within a 12-hour window after disease manifestation in NEC patients. High-performance liquid chromatography coupled with Q-TOF mass spectrometry (HPLC-QTOF-MS/MS) and 4D label-free quantitative proteomics were employed to detect differentially expressed proteins and small-molecule metabolites in plasma. Results Results revealed imbalances in amino acid metabolism pathways related to inflammatory processes during NEC progression, including γ-aminobutyric acid (GABA), arginine metabolism, and butyrate metabolism, as well as alterations in protein pathways such as glycolysis/gluconeogenesis, NOD-like receptor signaling, and Rap1 signaling. Conclusions Through integrated analysis of metabolomics and proteomics, this study suggests that butyrate metabolism may influence the pathogenesis of NEC via a non-canonical NOD-like receptor signaling pathway. This provides a highly promising approach for elucidating the pathogenesis of NEC in preterm infants, which offers new insights and evidence to advance disease understanding and intervention strategies.