Gene expression profiling in necrotizing enterocolitis reveals pathways common to those reported in Crohn’s disease

Abstract

BackgroundNecrotizing enterocolitis (NEC) is the most frequent life-threatening gastrointestinal disease experienced by premature infants in neonatal intensive care units. The challenge for neonatologists is to detect early clinical manifestations of NEC. One strategy would be to identify specific markers that could be used as early diagnostic tools to identify preterm infants most at risk of developing NEC or in the event of a diagnostic dilemma of suspected disease. As a first step in this direction, we sought to determine the specific gene expression profile of NEC.MethodsDeep sequencing (RNA-Seq) was used to establish the gene expression profiles in ileal samples obtained from preterm infants diagnosed with NEC and non-NEC conditions. Data were analyzed with Ingenuity Pathway Analysis and ToppCluster softwares.ResultsData analysis indicated that the most significant functional pathways over-represented in NEC neonates were associated with immune functions, such as altered T and B cell signaling, B cell development, and the role of pattern recognition receptors for bacteria and viruses. Among the genes that were strongly modulated in neonates with NEC, we observed a significant degree of similarity when compared with those reported in Crohn’s disease, a chronic inflammatory bowel disease.ConclusionsGene expression profile analysis revealed a predominantly altered immune response in the intestine of NEC neonates. Moreover, comparative analysis between NEC and Crohn’s disease gene expression repertoires revealed a surprisingly high degree of similarity between these two conditions suggesting a new avenue for identifying NEC biomarkers.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-016-0166-9) contains supplementary material, which is available to authorized users.

Prolonged Absence of Mechanoluminal Stimulation in Human Intestine Alters the Transcriptome and Intestinal Stem Cell Niche

“…Because all samples were obtained from children with previous NEC or focal intestinal perforation, we sought to determine whether the significant genes associated with immune and inflammatory processes were chronic changes induced by the initial inflammatory insult. Our data were compared with previously reported RNA sequencing–based gene expression profiles from preterm infants with NEC 36 . Comparison of significant pathways in the 2 gene sets showed that inflammation and regulation of inflammation both were over-represented.…”

RNA-Seq for Gene Expression Profiling of Human Necrotizing Enterocolitis: a Pilot Study

“…Recently, the first RNA-Seq for gene expression profiling in NEC was reported (31). This first RNA-Seq study used ileum tissues from preterm patients with other diseases for the control, and several genes associated with immune functions (in particular, genes associated with Crohn's disease) were identified as contributing factors to NEC development, together with other candidate genes.…”

“…In addition, normal tissues from the small bowel segment in infants without NEC or related diseases would have been ideal for the comparison analysis; however, it was limited to obtain these normal tissues. Although the first RNA-Seq analysis study of NEC used the ileum for the normal control (31), this study used adjacent normal tissues, and we do not rule out the possible effect of congenital diseases (such as small intestinal perforation, intestinal atresia, etc. ).…”

Microbiota regulate intestinal epithelial gene expression by suppressing the transcription factor Hepatocyte nuclear factor 4 alpha

“…5H-K). In contrast to IBD, analysis of intestinal transcriptomic data sets from human subjects with necrotizing enterocolitis (NEC) (Tremblay et al 2016) or insulin-resistance (IR) (Veilleux et al 2015) did not reveal strong enrichment of HNF4A-bound regions near down-regulated genes (Fig. 5C).…”