Multiple Opportunistic Pathogens, but Not Pre-existing Inflammation, May Be Associated with Necrotizing Enterocolitis

Steven T. Leach, Kei Lui, Zin Naing, Scot E. Dowd, Hazel M. Mitchell, Andrew S. Day

Necrotizing enterocolitis (NEC) leads to significant morbidity and mortality in the neonatal intensive care unit. Although current evidence would suggest that bacteria contribute to the pathogenesis of NEC, no single bacterium has yet been identified. The aims of this study were to investigate fecal S100A12 concentrations and the intestinal bacterial community in premature infants (24-32 weeks) and investigate any associations between the microbiota and the development of NEC. Meconium and feces were collected from premature newborn infants (between 24 and 32 weeks gestation) over the first 4 weeks of life. Fecal S100A12 concentrations were assayed by immunoassay, and samples were subject to 16S rDNA analysis using next-generation sequencing techniques. Fecal samples were collected from four infants that developed NEC and 18 control infants. Prior to developing NEC, fecal S100A12 concentrations were not elevated; however, following NEC diagnosis, concentrations were highly elevated. The fecal bacterial communities of infants with NEC did not differ significantly from control infants. However, potentially pathogenic bacteria were detected in significantly more infants with NEC than in controls (p = 0.0007). At birth, fecal S100A12 concentrations were not elevated in premature infants subsequently developing NEC in this cohort. Following NEC diagnosis, S100A12 concentrations were highly elevated, suggesting that this potentially could act as a marker of disease progression. Higher detection rates of potentially pathogenic bacteria in NEC infants suggest that a range of potentially pathogenic bacteria may collectively contribute to NEC pathogenesis.