Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) describes the chronic inflammations of parts of the intestine and is a collective of several further specified illnesses. The most common conditions are ulcerative colitis and Crohn's disease. It is classified as an autoimmune disease for which no cure has been developed. Current treatments include immunosuppression, surgery, antibiotics and nutritional therapies. This disease is a severe burden for the patients as well as it causes increasing direct (treatment) and indirect (absenteeism from work) costs for society. Furthermore, only in Europe 2.5 million people are affected by IBD and the number of cases is increasing world-wide¹.
Unfortunately there are no characteristic blood markers to distinguish the different forms of IBD. The diagnosis relies mostly on the location of inflammation observed during a colonoscopy. Also the underlying trigger of the disease is not completely understood but correlation studies proposed factors such as diet, genetic predisposition, breach of the intestinal barrier and unfavorable alteration of the microbiota, called dysbiosis². The diversity of the microbiota is noticeably reduced^2,2 in IBD patients and the composition of the gut flora changes from symbiotic to predominantly pathobiotic microbes¹.
The inflammation of the intestine partially interrupts the integrity of the layer of epithelial cells lining the intestine. This cell layer separates the gut lumen containing trillions of microbes from the body. The damage to this essential barrier compromises the selectivity and allows for penetration of immunogenic antigens from the lumen across the epithelial layer^1, which enhances the inflammation reaction.

Sensing of Markers for IBD

Beside the penetration of immunogenic antigens across the epithelial layer, there is also non-normal leakage of inflammation markers into the gut lumen. One of these molecules is nitric oxide (NO, t_1/2 < 6 seconds¹) and is one of the molecules we are going to sense with our system. The sensing of NO with E. coli has already been described by Archer et al.¹ in 2012. This work provides us with the relevant genetic elements and helps us to design this system for our purpose. Additionally, they present their system as a rapid detection system for IBD related disease flare-ups which would allow for an immediate intervention.
NorR is capable of binding NO with its mononuclear non-heme iron center. While other sensor proteins are not only specific for NO but also for other NO_s species, NorR binds specifically the NO^• radical.

References:

• [1] Maciej Chichlowski and Laura P Hale. “Bacterial-mucosal interactions in inflammatory bowel disease: an alliance gone bad”. In: American Journal of Physiology-Gastrointestinal and Liver Physiology 295.6 (2008), G1139–G1149.