title: Novel xylan-controlled delivery of therapeutic proteins to inflamed colon by the human anaerobic commensal bacterium.
abstract: BACKGROUND
  Growth factors such as keratinocyte growth factor-2 (KGF-2) and transforming growth factor-beta (TGF-β) are important immunoregulatory and epithelial growth factors. They are also potential therapeutic proteins for inflammatory bowel disease. However, owing to protein instability in the upper gastrointestinal tract, it is difficult to achieve therapeutic levels of these proteins in the injured colon when given orally. Furthermore, the short half-life necessitates repeated dosage with large amounts of the growth factor, which may have dangerous side effects, hence the importance of temporal and spatial control of growth factor delivery.
  
  
  METHODS
  The human commensal gut bacterium, Bacteroides ovatus, was genetically engineered to produce human KGF-2 or TGF-β1 (BO-KGF or BO-TGF) in a regulated manner in response to the dietary polysaccharide, xylan. The successful application of BO-KGF or BO-TGF in the prevention of dextran sodium sulphate induced murine colitis is presented here.
  
  
  RESULTS
  This novel drug delivery system had a significant prophylactic effect, limiting the development of intestinal inflammation both clinically and histopathologically. The ability to regulate heterologous protein production by B ovatus using xylan is both unique and an important safety feature of this drug delivery system.
  
  
  CONCLUSIONS
  The use of genetically engineered B ovatus for the controlled and localised delivery of epithelial growth promoting and immunomodulatory proteins has potential clinical applications for the treatment of various diseases targeting the colon.
authors.affiliation: University of Leeds, Insitute of Molecular and Cellular Biology, UK. zaed.hamady@doctors.org.uk
authors.forename: Z Z R
authors.initials: ZZ
authors.lastname: Hamady
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001439:Bacteroides; D001442:Bacteroides Infections / Q000188:drug therapy*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D016264:Dextran Sulfate; D016503:Drug Delivery Systems; D051526:Fibroblast Growth Factor 10 / Q000008:administration & dosage* / Q000494:pharmacology; D005818:Genetic Engineering; D007509:Irritants; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019936:Probiotics / Q000008:administration & dosage; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000494:pharmacology*; D014990:Xylans
chemical_list: D000893:Anti-Inflammatory Agents; D051526:Fibroblast Growth Factor 10; D007509:Irritants; D016212:Transforming Growth Factor beta; D014990:Xylans; D016264:Dextran Sulfate