Abstract

Inflammatory Bowel Disease (IBD) is characterised by chronic inflammation of the intestine. The condition is associated with an imbalance in immune cell populations, notably Th17 and Treg. Existing immunosuppressive therapies, when successful, often elicit systemic side effects and require frequent readministration. Our solution is to develop a probiotic strain that restores the Th17/Treg cell balance via secretion of IL-10 in response to nitric oxide in the intestinal lumen. Overshoot is prevented by an adenine riboswitch-sRNA construct which responds to extracellular adenosine, an indicator of the Treg cell population. Integration of separate stimuli in a dual feedback loop enables a more dynamic, robust response to the immune state of the body. Various features have been incorporated to maximise biological safety, including an inducible kill switch system. We believe our design offers a non-invasive, self-tuning therapeutic for IBD, with potential to replace conventional immunosuppressants in the treatment of gastrointestinal autoimmune disorders.