Microbial therapeutics for acute colitis based on genetically modified Lactococcus lactis hypersecreting IL-1Ra in mice

Abstract

Inflammatory bowel disease: Training bugs to deliver drugs Genetically reprogrammed bacteria can facilitate the efficient delivery of a therapeutic protein for treating inflammatory bowel disease (IBD). Interleukin 1 receptor antagonist (IL-1Ra) inhibits the immune cells that attack the intestinal lining in IBD patients, but current administration strategies are associated with serious side effects. Takeshi Shimosato and colleagues at Shinshu University in Nagano, Japan, have engineered the microbe Lactococcus lactis to secrete high levels of IL-1Ra. The researchers dosed mice orally with these bacteria, which released IL-1Ra into the intestinal tissue. This treatment proved safe and effectively reduced inflammation and associated symptoms in a mouse model of ulcerative colitis. L. lactis has previously been tested as a probiotic in clinical trials, and may therefore offer an appealing alternative to subcutaneous administration of IBD drugs in human patients.