Microbiota-associated intestinal methylation changes confer immune-metabolic gene network of NEC in preterm pig model. Sus scrofa

Intestinal microbiota colonization is important for intestinal development and health of preterm infants, especially those with extremely low birth weight. Recent studies indicated for a dynamic crosstalk between that gut microbiota and DNA methylome of host intestinal cells. Thereby, we sought to determine the epigenomic and metagenomic consequences of suppression of microbiota colonization in the intestine of preterm neonates to gain insights into biological pathways that shape the interface between the gut microbiota and the preterm intestinal cells. We examined 14 preterm piglets by comparing the conventional preterm neonates with those ones treated with oral antibiotics for genome wide DNA methylation and 16S rDNA microbiome. Our results demonstrated an extensive genome-wide DNA methylation changes in response to the suppression of intestinal microbe colonization, especially genes involved in neonatal immune response signaling and glycol-metabolism pathways were identified. Our study highlights several key genes that might predispose preterm neonates to NEC risk due to their key roles involved in the immune-metabolic networks. Our study not only provided rich omic-data to interpret molecular program in relation with microbiota-associated methylome-proteome network changes, but also confer clinical usage of key gene markers for potential early diagnostics of NEC of preterm neonates. Overall design: Fourteen piglets from three sows (Danish Landrace x Large White x Duroc) were Caesarean-delivered at preterm (d 106 or 90% of gestation), which was established as a model for the preterm human infant at approximately 70% gestation due to the intestinal maturity. Pigs were randomized according to birth weight and sex into two groups: half were conventionally raised with spontaneous commensal microbiota colonization by receiving saline through orogastric catheter (CON group, n=7) and the other half with delayed colonization by receiving broad-spectrum antibiotics through orogastric catheter (OAB group, n=7).