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Research ArticleExperimental Studies

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

XICHEN ZHANG, RENEE FISHER, WEN HOU, DONNA SHIELDS, MICHAEL W. EPPERLY, HONG WANG, LIANG WEI, BRIAN J. LEIBOWITZ, JIAN YU, LAURA M. ALEXANDER, JAN-PETER VAN PIJKEREN, SIMON WATKINS, PETER WIPF and JOEL S. GREENBERGER
In Vivo January 2020, 34 (1) 39-50; DOI: https://doi.org/10.21873/invivo.11743
XICHEN ZHANG
1Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, U.S.A.
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RENEE FISHER
1Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, U.S.A.
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WEN HOU
1Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, U.S.A.
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DONNA SHIELDS
1Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, U.S.A.
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MICHAEL W. EPPERLY
1Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, U.S.A.
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HONG WANG
2Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, U.S.A.
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LIANG WEI
3Department of Pathology, University of Pittsburgh, Pittsburgh, PA, U.S.A.
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BRIAN J. LEIBOWITZ
3Department of Pathology, University of Pittsburgh, Pittsburgh, PA, U.S.A.
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JIAN YU
3Department of Pathology, University of Pittsburgh, Pittsburgh, PA, U.S.A.
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LAURA M. ALEXANDER
4Department of Food Science, University of Wisconsin-Madison, Madison, WI, U.S.A.
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JAN-PETER VAN PIJKEREN
4Department of Food Science, University of Wisconsin-Madison, Madison, WI, U.S.A.
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SIMON WATKINS
5Center for Imaging, Department of Pathology, University of Pittsburgh, Pittsburgh, PA, U.S.A.
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PETER WIPF
6Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, U.S.A.
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JOEL S. GREENBERGER
1Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, U.S.A.
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  • For correspondence: greenbergerjs{at}upmc.edu
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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.

  • Lactobacillus reuteri
  • E. coli
  • interleukin-22
  • total body irradiation
  • radiation mitigators
  • Received August 19, 2019.
  • Revision received September 21, 2019.
  • Accepted September 27, 2019.
  • Copyright © 2020 The Author(s). Published by the International Institute of Anticancer Research.
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Second-generation Probiotics Producing IL-22 Increase Survival of Mice After Total Body Irradiation
XICHEN ZHANG, RENEE FISHER, WEN HOU, DONNA SHIELDS, MICHAEL W. EPPERLY, HONG WANG, LIANG WEI, BRIAN J. LEIBOWITZ, JIAN YU, LAURA M. ALEXANDER, JAN-PETER VAN PIJKEREN, SIMON WATKINS, PETER WIPF, JOEL S. GREENBERGER
In Vivo Jan 2020, 34 (1) 39-50; DOI: 10.21873/invivo.11743

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Second-generation Probiotics Producing IL-22 Increase Survival of Mice After Total Body Irradiation
XICHEN ZHANG, RENEE FISHER, WEN HOU, DONNA SHIELDS, MICHAEL W. EPPERLY, HONG WANG, LIANG WEI, BRIAN J. LEIBOWITZ, JIAN YU, LAURA M. ALEXANDER, JAN-PETER VAN PIJKEREN, SIMON WATKINS, PETER WIPF, JOEL S. GREENBERGER
In Vivo Jan 2020, 34 (1) 39-50; DOI: 10.21873/invivo.11743
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Keywords

  • Lactobacillus reuteri
  • E. coli
  • interleukin-22
  • total body irradiation
  • radiation mitigators
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