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Second-generation Probiotics Producing IL-22 Increase Survival of Mice After Total Body Irradiation

2019; Stanford University Highwire Press; Volume: 34; Issue: 1 Linguagem: Inglês

10.21873/invivo.11743

1791-7549

Xichen Zhang, Renee Fisher, Wen‐Chi Hou, Donna Shields, Michael W. Epperly, Hong Wang, Liang Wei, Brian J. Leibowitz, Jian Yu, Laura M. Alexander, Jan‐Peter van Pijkeren, Simon C. Watkins, Peter Wipf, Joel S. Greenberger,

Diet and metabolism studies

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.