Plasma Metabolomics to Evaluate Progression of Necrotising Enterocolitis in Preterm Pigs

Abstract

Necrotising enterocolitis (NEC) is a microbiome-dependent gut disease in preterm infants in early life. Antibiotic treatment is a common intervention for NEC. How NEC lesions, with or without antibiotics, affect plasma metabolome was explored in this study. Formula-fed preterm pigs were used as a model for human NEC and treated with saline, parenteral or oral antibiotics (n = 15–17) for four days after delivery. Gut tissues were collected for evaluation of NEC-like lesions and plasma for metabolomic analysis by proton nuclear magnetic resonance spectroscopy (1H-NMR). Metabolites were annotated, quantified and subjected to statistical modelling to delineate the effects of NEC and antibiotic treatment. Presence of severe NEC lesions, not antibiotic treatment, was the main drive for plasma metabolite changes. Relative to other pigs, pigs with severe NEC lesions had higher levels of alanine, histidine and myo-inositol, and lower levels of 3-hydroxybutyric acid and isobutyric acid. Across NEC lesion states (healthy, mild, severe), antibiotics directly affected only a few metabolites (tryptophan, 3-phenyllactic acid). Together and independently, NEC and antibiotic treatment affected circulating metabolites in preterm pigs. Amino acids and plasma metabolites, partly related to the gut microbiome, may be helpful to monitor progression of NEC lesions after proper validation.

Analysis of serum metabolism in premature infants before and after feeding using GC–MS and the relationship with necrotizing enterocolitis

“…Exploring the relationship between multiple metabolites through multidimensional models is expected to provide a new means for the early prediction of related diseases, especially inflammatory bowel diseases, such as NEC, that are prone to occur after feeding premature infants (Fanos et al, 2013 ). We can even prevent the occurrence of NEC by interfering with metabolic pathways, as shown in animal models (Jiang et al, 2021 ).…”

Gut Microbiome–Brain Axis as an Explanation for the Risk of Poor Neurodevelopment Outcome in Preterm Infants with Necrotizing Enterocolitis

“…A longitudinal study comparing metabolites in urine samples of NEC preterm infants compared with a control group without NEC used proton nuclear magnetic resonance spectroscopy ( 1 H NMR) to find that late-onset NEC was associated with high lactate and decreased betaine, creatine, urea, myo-inositol, and N,N-dimethylglycine [61]. An animal study using preterm pigs as a model for NEC found higher serum levels of alanine, histidine, and myo-inositol and lower levels of 3-hydroxybutyric acid and isobutyric acid in animals with NEC [62]. Targeted metabolomics analysis of NEC and control fecal samples found that fecal fomic acid (fomate) was significantly increased at NEC onset and decreased with recovery [63].…”