Xichen Zhang1, Renee Fisher1, Wen Hou1, Donna Shields1, Michael W Epperly1, Hong Wang2, Liang Wei3, Brian J Leibowitz3, Jian Yu3, Laura M Alexander4, Jan-Peter VAN Pijkeren4, Simon Watkins5, Peter Wipf6, Joel S Greenberger7. 1. Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, U.S.A. 2. Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, U.S.A. 3. Department of Pathology, University of Pittsburgh, Pittsburgh, PA, U.S.A. 4. Department of Food Science, University of Wisconsin-Madison, Madison, WI, U.S.A. 5. Center for Imaging, Department of Pathology, University of Pittsburgh, Pittsburgh, PA, U.S.A. 6. Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, U.S.A. 7. Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, U.S.A. greenbergerjs@upmc.edu.
Abstract
BACKGROUND/AIM: Intestinal damage induced by total body irradiation (TBI) reduces leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5)-expressing stem cells, goblet, and Paneth cells, breaching the epithelial lining, and facilitating bacterial translocation, sepsis, and death. MATERIALS AND METHODS: Survival was measured after TBI in animals that received wild-type or recombinant bacteria producing interleukin-22 (IL-22). Changes in survival due to microbially delivered IL-22 were measured. Lactobacillus reuteri producing IL-22, or Escherichia coli-IL-22 were compared to determine which delivery system is better. RESULTS: C57BL/6 mice receiving IL-22 probiotics at 24 h after 9.25 Gy TBI, demonstrated green fluorescent protein-positive bacteria in the intestine, doubled the number of Lgr5+ intestinal stem cells, and increased 30-day survival. Bacteria were localized to the jejunum, ileum, and colon. CONCLUSION: Second-generation probiotics appear to be valuable for mitigation of TBI, and radiation protection during therapeutic total abdominal irradiation. Copyright
BACKGROUND/AIM: Intestinal damage induced by total body irradiation (TBI) reduces leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5)-expressing stem cells, goblet, and Paneth cells, breaching the epithelial lining, and facilitating bacterial translocation, sepsis, and death. MATERIALS AND METHODS: Survival was measured after TBI in animals that received wild-type or recombinant bacteria producing interleukin-22 (IL-22). Changes in survival due to microbially delivered IL-22 were measured. Lactobacillus reuteri producing IL-22, or Escherichia coli-IL-22 were compared to determine which delivery system is better. RESULTS: C57BL/6 mice receiving IL-22 probiotics at 24 h after 9.25 Gy TBI, demonstrated green fluorescent protein-positive bacteria in the intestine, doubled the number of Lgr5+ intestinal stem cells, and increased 30-day survival. Bacteria were localized to the jejunum, ileum, and colon. CONCLUSION: Second-generation probiotics appear to be valuable for mitigation of TBI, and radiation protection during therapeutic total abdominal irradiation. Copyright
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