Mechanisms Affecting the Gut of Preterm Infants in Enteral Feeding Trials

Bovine lactoferrin to reduce late onset sepsis (LOS) in infants <32 weeks was explored in the placebo controlled Enteral Lactoferrin in Neonates (ELFIN) trial. Mechanisms Affecting the Gut of Preterm Infants in Enteral feeding studies (MAGPIE) analysed non-invasively collected samples of stool and urine, along with residual resected gut tissue if infants required surgery from ELFIN participants to determine any mechanistic impact of lactoferrin. Thirteen UK NICUs were involved, recruiting 479 preterm infants. Trial interventions involved effects on gut microbes, metabolites, and aspects of host immune function. Current hypotheses suggest that NEC and/or LOS are due to a dysregulated immune system in the context of gut dysbiosis, but mechanisms have not been systematically studied within large RCTs. Microbiomic analysis was conducted using 16S rRNA gene sequencing, and metabolites were assessed by mass spectrometry to detect volatile organic and other compounds produced by microbes or the host. We will explored differences between disease cases and controls, as well as exploring the actions of trial interventions. We undertook microbiome analyses of 1304 samples (201 infants), LC-MS analyses of 171 stools (83 infants) and 225 urines (90 infants), and GC-MS Volatile Organic Compound (VOC) analyses of 314 stools (117 infants).The MAGPIE study is funded by the UK NIHR Efficacy and Mechanistic Evaluation programme.(ISRCTN 12554594).