Biomarkers of human gastro-intestinal tract regions

Background and aims: Dysregulation of intestinal epithelial cells performance associates with an array of pathologies whose onset mechanisms are incompletely understood. The aim of the present study was to provide a map of gene expresssion patterns along the human healthy adult gastro-intestinal tract and to implement a new procedure for microarray data noise filtering that would allow their use as a reference when screening for pathological deviations, such as inflammatory bowel disease (IBD). Methods: Gene expression profiles in antrum, duodenum, jejunum, ileum and transverse colon biopsies were measured with the Affymetrix U133A array and principal component analysis was used to identify region-selective biomarkers. These data were intersected with highly variable genes from a public dataset of gene expression in the ileal and colonic healthy regions of UC and Crohn’s disease patients. Moreover, gene sets covering gut functions not entirely accounted for by the available public tools were constructed to monitor their expression along the GI tract. Results: 166 genes were found to be responsible for distinguishing the five regions considered. Fourteen had never been described in the GI tract, including a semaphorin probably implicated in pathogen invasion, and six other novel genes. Similar analysis of the IBD datasets revealed that samples stratify based on disease rather than on the intestinal region. This withstanding, eleven genes were identified as possible early predictors of Crohn’s and/or UC in ileum and/or colon. These include CLCA4 and SLC26A2, both implicated in ion transport. Conclusions: This novel approach, validated by retrieving known gene profiles, allowed the identification of promising new leads both in health and IBD state. Keywords: gastro-intestinal tract comparison Biopsies were collected by endoscopy and colonoscopy from the antrum, duodenum, jejunum, ileum and transverse colon of two male and two female healthy human subjects, previous approval by the Ethical Committee of the Canton de Vaud, Lausanne, Switzerland. All surgical procedures were performed by a gastroenterologist at the University Hospital of the Canton de Vaud (CHUV), Lausanne, Switzerland. The individuals, informed about the scopes of the study, were aged 20-30 years, did not present any gastro-intestinal or cardio-vascular disorder, did not use any drug during 4 weeks before sampling and were Helicobacter pylori negative. The biopsies were snap-frozen and stored at –80 °C.