Monitoring of inflammatory bowel disease in children via DNA methylation patterns in stool

Inflammatory bowel disease (IBD) disease affects 40,000 people in Israel, 2,500 of which are children. There is an unmet need for a biomarker that allows identifying an inflammatory process in a specific segment of the intestine, to assess involvement of specific cell types and to dynamically monitor intestinal dynamics in patients. Such a biomarker could lead to major changes in prevention and treatment.

We have developed a novel platform for minimally invasive assessment of turnover rates of specific cell types in humans, based on DNA methylation patterns in body fluids. We hypothesize that detailed analysis of cell-free DNA fragments in stool can reveal important information about onset, location, and dynamics of IBD.

To this end we have established a cocktail of methylation markers for cell types relevant to IBD including epithelial cells of specific segments of the intestine (stomach, duodenum, colon), and multiple immune cell type. We have started to characterize these markers in stool samples collected from healthy individuals and patients with IBD. We find that patients with IBD have elevated levels of human DNA in stool compared with healthy individuals or patients with irritable bowel syndrome (IBS), and that the concentration of human DNA in stool is correlated to disease severity. Methylation analysis revealed that most human DNA in the stool of patients originates from leukocytes, with a significant contribution of intestinal epithelial cells. These findings suggest that stool contains information regarding inflammatory processes taking place in the gut, which can potentially be used to better understand the dynamics of IBD.