Emerging Biomarkers for Prediction and Early Diagnosis of Necrotizing Enterocolitis in the Era of Metabolomics and Proteomics

Abstract

Necrotizing Enterocolitis (NEC) is a catastrophic disease affecting predominantly premature infants and is characterized by high mortality and serious long-term consequences. Traditionally, diagnosis of NEC is based on clinical and radiological findings, which, however, are non-specific for NEC, thus confusing differential diagnosis of other conditions such as neonatal sepsis and spontaneous intestinal perforation. In addition, by the time clinical and radiological findings become apparent, NEC has already progressed to an advanced stage. During the last three decades, a lot of research has focused on the discovery of biomarkers, which could accurately predict and make an early diagnosis of NEC. Biomarkers used thus far in clinical practice include acute phase proteins, inflammation mediators, and molecules involved in the immune response. However, none has been proven accurate enough to predict and make an early diagnosis of NEC or discriminate clinical from surgical NEC or other non-NEC gastrointestinal diseases. Complexity of mechanisms involved in NEC pathogenesis, which remains largely poorly elucidated, could partly explain the unsatisfactory diagnostic performance of the existing NEC biomarkers. More recently applied technics can provide important insight into the pathophysiological mechanisms underlying NEC but can also aid the detection of potentially predictive, early diagnostic, and prognostic biomarkers. Progress in omics technology has allowed for the simultaneous measurement of a large number of proteins, metabolic products, lipids, and genes, using serum/plasma, urine, feces, tissues, and other biological specimens. This review is an update of current data on emerging NEC biomarkers detected using proteomics and metabolomics, further discussing limitations and future perspectives in prediction and early diagnosis of NEC.

Knowledge gaps in late-onset neonatal sepsis in preterm neonates: a roadmap for future research

“…69,179 Development of predictive modeling dashboards will require harmonized and large-scale databases, fed by multicentre collaborations, if possible including proteomics and/or metabolomics data. 180 A ROADMAP FOR FUTURE RESEARCH In conclusion, the research field of LONS, is entering an exciting new era. The availability of computational power, computational medicine algorithms, and hypothesis-free -omics approaches give way to building bedside feedback tools to guide clinicians in personalized management of LONS.…”

Association of neutrophil to lymphocyte ratio with preterm necrotizing enterocolitis: a retrospective case-control study

“…It has been reported that NEC prevalence is 5–7% in very low birth weight (VLBW) infants [ 1 ], 20–30% of whom eventually die [ 2 ]. Moreover, NEC survivors have a high risk of severe long-term complications, such as short bowel syndrome, growth delay, and neurodevelopmental sequelae, which are associated with a low quality of future individual life and increasing long-term social health care costs [ 3 ]. It is a multifactorial disease in which the exact pathogenesis remains elusive.…”

“…In the present clinical practice, biomarkers currently include acute phase proteins, inflammatory mediators, and immunoreactive molecules. Nonetheless, the early prediction and diagnosis of NEC, or the ability to discriminate different stages of NEC correctly from other gastrointestinal diseases, remains unresolved [ 3 ]. To our knowledge, there was no single biomarker or cluster of biomarkers that meet the neonatologists’ satisfaction.…”

Urine NMR Metabolomics Profile of Preterm Infants With Necrotizing Enterocolitis Over the First Two Months of Life: A Pilot Longitudinal Case-Control Study

“…Recommendations on feeding practices, such as breastfeeding, the proper management of feeding intolerance, the application of feeding guidelines, and the implementation of probiotics with diet, can prevent NEC onset in critically ill newborns admitted in NICU ( Bi et al, 2019 ). Several studies, recently revised in an elegant review ( Agakidou et al, 2020 ), have investigated the metabolic profile of blood, plasma, serum, urine, stools, and intestinal epithelial cells in preterm neonates with NEC, opening new horizons on the molecular mechanisms associated with the disease and searching candidate biomarkers for the early diagnosis and prognosis of NEC. This pilot study aimed to explore the presence of the urinary metabolic signature in VLBW preterm newborns by using a proton nuclear magnetic resonance spectroscopy ( 1 H NMR)-based metabolomic approach.…”