Exposure to the gut microbiota drives distinct methylome and transcriptome changes in intestinal epithelial cells during postnatal development

作者：W. Pan, F. Sommer, M. Falk-Paulsen, T. Ulas, P. Best, A. Fazio, P. Kachroo, A. Luzius, Marlene Jentzsch, A. Rehman, Fabian Müller, Thomas Lengauer, J. Walter, Sven Künzel, J. Baines, S. Schreiber, A. Franke, J. Schultze, F. Bäckhed, P. Rosenstiel · 发表于：Genome Medicine · 年份：2018 · DOI：10.1186/s13073-018-0534-5 · 被引用次数：138 · 研究领域：Biology、Medicine

The interplay of epigenetic processes and the intestinal microbiota may play an important role in intestinal development and homeostasis. Previous studies have established that the microbiota regulates a large proportion of the intestinal epithelial transcriptome in the adult host, but microbial effects on DNA methylation and gene expression during early postnatal development are still poorly understood. Here, we sought to investigate the microbial effects on DNA methylation and the transcriptome of intestinal epithelial cells (IECs) during postnatal development. We collected IECs from the small intestine of each of five 1-, 4- and 12 to 16-week-old mice representing the infant, juvenile, and adult states, raised either in the presence or absence of a microbiota. The DNA methylation profile was determined using reduced representation bisulfite sequencing (RRBS) and the epithelial transcriptome by RNA sequencing using paired samples from each individual mouse to analyze the link between microbiota, gene expression, and DNA methylation. We found that microbiota-dependent and -independent processes act together to shape the postnatal development of the transcriptome and DNA methylation signatures of IECs. The bacterial effect on the transcriptome increased over time, whereas most microbiota-dependent DNA methylation differences were detected already early after birth. Microbiota-responsive transcripts could be attributed to stage-specific cellular programs during postnatal devel...