Multi-omics insights into immunometabolic dysregulation in neonatal sepsis for precision medicine.

Neonatal sepsis remains a major global health challenge, contributing substantially to morbidity and mortality despite many advances. Conventional diagnostics often fail to capture the disease complexity and immune dysregulation, leading to delayed diagnosis and sub-optimal treatment. Recent advances in multiomics, including genomics, transcriptomics, proteomics, metabolomics and metagenomics are transforming molecular understanding by enabling a precise view of host-pathogen interactions. These approaches also provide critical insights into metainflammation, a state of chronic, low-grade immune and metabolic dysregulation, playing a pivotal role in neonatal immune vulnerability. Integrating multi-omics with meta-inflammatory profiling may support future risk stratification, biomarker discovery, and precision-oriented neonatal sepsis care. However, clinical translation requires further validation, platform standardization, and feasibility assessment in NICU settings. Such insights may establish the foundation of P4 medicine by emphasizing prediction, prevention, personalisation, and participation in neonatal care. Multi-omics integration may support endotype identification, and data-driven clinical communication after adequate validation. Overall, this review highlights how multiomics and metainflammation driven frameworks may improve mechanistic understanding of neonatal sepsis and guide future development of clinically feasible precision-medicine approaches.