TY - JOUR

T1 - Early microbial colonization affects DNA methylation of genes related to intestinal immunity and metabolism in preterm pigs

AU - Pan, Xiaoyu

AU - Gong, Desheng

AU - Nguyen, Duc Ninh

AU - Zhang, Xinxin

AU - Hu, Qi

AU - Lu, Hanlin

AU - Fredholm, Merete

AU - Sangild, Per T

AU - Gao, Fei

N1 - © The Author(s) 2018. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

PY - 2018

Y1 - 2018

N2 - Epigenetic regulation may play an important role in mediating microbe-host interactions and adaptation of intestinal gene expression to bacterial colonization just after birth. This is particularly important after preterm birth because the immature intestine is hypersensitive to invading bacteria. We compared the intestinal DNA methylome and microbiome between conventional (CON) and antibiotics-treated (AB) preterm pigs, used as a model for preterm infants. Oral AB treatment reduced bacterial density (∼100-fold), diversity and fermentation, improved the resistance to necrotizing enterocolitis (NEC) and changed the genome-wide DNA methylation in the distal small intestine. Integration of epigenome data with previously obtained proteome data showed that intestinal immune-metabolic pathways were affected by the AB-induced delay in bacterial colonization. DNA methylation and expression of intestinal genes, related to innate immune response, phagocytosis, endothelial homeostasis and tissue metabolism (e.g. CPN1, C3, LBP, HIF1A, MicroRNA-126, PTPRE), differed between AB and CON pigs even before any evidence of NEC lesions. Our findings document that the newborn immature intestine is influenced by bacterial colonization via DNA methylation changes. 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 neonates.

AB - Epigenetic regulation may play an important role in mediating microbe-host interactions and adaptation of intestinal gene expression to bacterial colonization just after birth. This is particularly important after preterm birth because the immature intestine is hypersensitive to invading bacteria. We compared the intestinal DNA methylome and microbiome between conventional (CON) and antibiotics-treated (AB) preterm pigs, used as a model for preterm infants. Oral AB treatment reduced bacterial density (∼100-fold), diversity and fermentation, improved the resistance to necrotizing enterocolitis (NEC) and changed the genome-wide DNA methylation in the distal small intestine. Integration of epigenome data with previously obtained proteome data showed that intestinal immune-metabolic pathways were affected by the AB-induced delay in bacterial colonization. DNA methylation and expression of intestinal genes, related to innate immune response, phagocytosis, endothelial homeostasis and tissue metabolism (e.g. CPN1, C3, LBP, HIF1A, MicroRNA-126, PTPRE), differed between AB and CON pigs even before any evidence of NEC lesions. Our findings document that the newborn immature intestine is influenced by bacterial colonization via DNA methylation changes. 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 neonates.

U2 - 10.1093/dnares/dsy001

DO - 10.1093/dnares/dsy001

M3 - Journal article

C2 - 29365082

VL - 25

SP - 287

EP - 296

JO - DNA Research

JF - DNA Research

SN - 1340-2838

IS - 3

ER -