Systems medicine for bowel disease

Approximately one in 10 000 people in Europe suffer from ulcerative colitis or Crohn's disease, the most common clinical manifestations of IBD. The disease is incurable and requires lifelong management.

Systems biology builds mathematical models of complex biological processes on extensive experimental data. The scope of the EU-funded SYSMEDIBD (Systems medicine of chronic inflammatory bowel disease) is to use a systems medicine approach for IBD. The plan is to collect data and incorporate it into mathematical models that could apply towards disease management, biomarker discovery and patient stratification.

From a scientific perspective, SYSMEDIBD scientists are working to elucidate the regulation of transcriptional networks in IBD, with particular focus on NF-kappa-B signalling. In this context, they have generated transgenic mice expressing fluorescent proteins of the NF-kappa-B pathway.

Preliminary insight into the dynamics of NF-kappa-B signalling indicates that the oscillation frequency is different in different cell types and not all cells respond similarly to NF-kappa-B pathway signals. In addition, researchers used small molecules that interfere with NF-kappa-B oscillation, opening up new avenues for therapeutic targeting.

To extrapolate these results in humans, research teams have produced humanised mouse models containing human gut tissue and immune cells. This invaluable tool will allow studying of NF-kappa-B dynamics in human tissue. Gene expression analysis in these mice and in patient samples should reveal further therapeutic targets for IBD as well as biomarkers associated with disease severity. Some of these biomarkers could serve as diagnostic indicators.

During the next phase of the project, the consortium will perform prospective analysis of IBD patients from Maastricht to discover the course of the disease, episodes of gut inflammation and successful treatment regimes.

Overall, the SYSMEDIBD results will help comprehend IBD aetiology, facilitate prompt diagnosis and propose novel treatments.