Research ArticleInflammatory Bowel Diseases

Food-Grade Bacteria Expressing Elafin Protect Against Inflammation and Restore Colon Homeostasis

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Science Translational Medicine  31 Oct 2012:
Vol. 4, Issue 158, pp. 158ra144
DOI: 10.1126/scitranslmed.3004212

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Bugs Deliver Drug and Keep the Gut Happy

Elafin is a natural protease inhibitor that is normally expressed by the human intestine and protects the gut from insults. Elafin expression is lost in patients suffering from inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis. In a new study, Motta et al. tested whether delivery of human Elafin directly into the gut would protect from inflammatory insults and restore gut homeostasis. They commandeered helpful, safe bacteria that are commonly present in the gut and in food products and genetically modified the bacteria so that they would produce Elafin. They introduced the human Elafin gene into Lactococcus lactis and Lactobacillus casei, two bacteria present in dairy food. When given orally to mice, the two strains of genetically modified bacteria were detected a few hours later at the surface of the intestine, where they produced human Elafin. In different mouse models of acute or chronic intestinal inflammation, oral treatment with Elafin-expressing food-grade bacteria protected the gut from inflammatory damage. Elafin-expressing bacteria were also able to protect cultured human intestinal cells from inflammatory insults and to restore homeostasis and physiological functions. This approach may offer a safe, cost-effective long-term treatment for inflammatory bowel diseases.