Oral antibiotic treatment in the 5 days after birth delayed bacterial colonization. This seems to provide lower immune response, less hypoxic stress, better vascular integrity and increased metabolism in the immature intestine via epigentic mechanisms.
The initial bacterial colonization of gut in early life of infants is critical because the microbiota shapes development of immunity and has effects on metabolism. Preterm infants are supersensitive to invading pathogens due to their immature intestine and 10% of all hospitalized preterm infants suffer from necrotizing enterocolitis (NEC). The initial essential bacterial colonization of beneficial microbes is thus delicate as the innate immune response is underdeveloped and less sensitive to harmful microbes. Nevertheless, the development of balanced host-microbe interactions is critical for the adaptation of the newborn to the external environment.
Preventive steps towards NEC include antibiotics, probiotics and prebiotics. Delaying bacterial colonization by oral administration of antibiotics for the first few days of life decrease NEC incidences in preterm infants and pigs. However, antibiotics are not used in clinical practice, mainly due to concerns of increased antibiotic resistance. Thus, it is important to identify pathways that are affected by bacterial colonization and new ways to prevent microbe-induced intestinal dysfunction and NEC.
A comparison of the intestinal DNA methylome and microbiome between conventional and antibiotics-treated preterm pigs was used as a model for preterm infants.
Oral treatment with antibiotics in the first 5 days of life reduced bacterial density (∼100-fold), diversity and fermentation, improved the resistance to NEC, and changed the genome-wide DNA methylation in the distal small intestine. Also, the DNA methylation and expression of intestinal genes, related to innate immune response, phagocytosis, endothelial homeostasis and tissue metabolism differed between conventional and antibiotics-treated pigs.
These findings document that the newborn immature intestine is influenced by bacterial colonization via DNA methylation changes. Such microbiota-dependent epigenetic programming of genes related to gut immunity, vascular integrity and metabolism may be critical for short- and long-term intestinal health in preterm neonate infants.