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Building better bugs to deliver biologics in intestinal inflammation
  1. Kim E Barrett
  1. Division of Gastroenterology, Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, California, USA
  1. Correspondence to Professor Kim E Barrett, University of California, San Diego, Mailcode 0063, 9500 Gilman Drive, La Jolla, CA 92093-0063, USA; kbarrett{at}

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Despite intense effort, the inflammatory bowel diseases (IBDs) of ulcerative colitis and Crohn's disease lack fully effective therapies for all patients. Current therapies include small molecules (anti-inflammatory agents and immunosuppressives) as well as biologics, which predominantly are antibody-based therapeutics that target specific facets of the inflammatory cascade, such as cytokines.1 Small molecule therapeutics suffer from their lack of specificity and thus the potential for significant side effects; this is particularly the case for systemic steroids, which remain the mainstay of therapy for many patients with severe IBD.2 3 Likewise, biologics, such as humanised antibodies that are directed against tumour necrosis factor α (TNFα), are expensive, require intravenous administration, and also suffer from the potential for side effects such as non-specific immunosuppression.4 Thus, in the absence of current information that would allow for a cure, patients with IBD are in great need of additional therapies that might modify their disease processes without a risk for unacceptable side effects.

To bypass some of the limitations associated with the use of biologic agents in IBD, some years ago, Steidler and colleagues published proof-of-principle experiments showing that probiotic micro-organisms could be engineered to express anti-inflammatory factors (in this particular example, the immunosuppressive cytokine interleukin 10 (IL10)), and that this could be shown to ameliorate bowel inflammation in an animal model of colitis.5 However, in these experiments it was not possible to control …

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