We read with great interest the detailed and informative investigation of multi-omics analysis of intestinal epithelial cells (IEC) collected from pediatric patients with inflammatory bowel disease by Howell et al.1 The authors have shown specific profiles of DNA methylation and transcriptome patterns in IECs, which enabled them to differentiate children diagnosed with Crohn’s disease or ulcerative colitis from healthy controls. The authors stated that majority of previous studies concerning the epigenetic changes that occur in inflammatory bowel disease were performed on mixed cell tissue samples, because of which IEC-specific epigenetic changes could have been misinterpreted.