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Intestinal Radiation Protection and Mitigation by Second-Generation Probiotic Lactobacillus-reuteri Engineered to Deliver Interleukin-22

Espinal, Alexis and Epperly, Michael W. and Mukherjee, Amitava and Fisher, Renee and Shields, Donna and Wang, Hong and Huq, M. Saiful and Hamade, Diala Fatima and Vlad, Anda M. and Coffman, Lan and Buckanovich, Ronald and Yu, Jian and Leibowitz, Brian J. and van Pijkeren, Jan-Peter and Patel, Ravi B. and Stolz, Donna and Watkins, Simon and Ejaz, Asim and Greenberger, Joel S. (2022) Intestinal Radiation Protection and Mitigation by Second-Generation Probiotic Lactobacillus-reuteri Engineered to Deliver Interleukin-22. International Journal of Molecular Sciences, 23 (10). p. 5616. ISSN 1422-0067

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1) Background: The systemic administration of therapeutic agents to the intestine including cytokines, such as Interleukin-22 (IL-22), is compromised by damage to the microvasculature 24 hrs after total body irradiation (TBI). At that time, there is significant death of intestinal microvascular endothelial cells and destruction of the lamina propria, which limits drug delivery through the circulation, thus reducing the capacity of therapeutics to stabilize the numbers of Lgr5+ intestinal crypt stem cells and their progeny, and improve survival. By its direct action on intestinal stem cells and their villus regeneration capacity, IL-22 is both an ionizing irradiation protector and mitigator. (2) Methods: To improve delivery of IL-22 to the irradiated intestine, we gavaged Lactobacillus-reuteri as a platform for the second-generation probiotic Lactobacillus-reuteri-Interleukin-22 (LR-IL-22). (3) Results: There was effective radiation mitigation by gavage of LR-IL-22 at 24 h after intestinal irradiation. Multiple biomarkers of radiation damage to the intestine, immune system and bone marrow were improved by LR-IL-22 compared to the gavage of control LR or intraperitoneal injection of IL-22 protein. (4) Conclusions: Oral administration of LR-IL-22 is an effective protector and mitigator of intestinal irradiation damage.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Espinal, Alexisame96@pitt.eduame96
Epperly, Michael W.epperly@pitt.eduepperly
Mukherjee, Amitavaamm223@pitt.eduamm2230000-0001-5603-5147
Fisher, Reneerlr45@pitt.edurlr45
Shields, Donnashieldsd@pitt.edushieldsd
Wang, Honghow8@pitt.eduhow8
Huq, M. Saifulmsh34@pitt.edumsh34
Hamade, Diala Fatima
Vlad, Anda M.anvst12@pitt.eduanvst12
Coffman, Lanlgc14@pitt.edulgc14
Buckanovich, Ronaldrjb101@pitt.edurjb101
Yu, Jianjiy3@pitt.edujiy30000-0002-4021-1000
Leibowitz, Brian J.bjl40@pitt.edubjl40
van Pijkeren, Jan-Peter
Patel, Ravi B.rbp27@pitt.edurbp27
Stolz, Donnadonna.stolz@pitt.edudonna.stolz
Watkins, Simonswatkins@pitt.eduswatkins
Ejaz, Asimasa118@pitt.eduasa118
Greenberger, Joel S.joelg@pitt.edujoelg0000-0003-2271-7566
Centers: Other Centers, Institutes, Offices, or Units > Hillman Cancer Center
Date: 17 May 2022
Date Type: Publication
Journal or Publication Title: International Journal of Molecular Sciences
Volume: 23
Number: 10
Publisher: MDPI AG
Page Range: p. 5616
DOI or Unique Handle: 10.3390/ijms23105616
Schools and Programs: School of Public Health > Biostatistics
Refereed: Yes
Uncontrolled Keywords: ionizing irradiation, whole abdomen irradiation, radioprotection, radiation mitigation, Lactobacillus reuteri-IL-22
ISSN: 1422-0067
Official URL:
Funders: National Institute of Allergy and Infectious Diseases
Article Type: Research Article
Date Deposited: 06 Jun 2022 15:39
Last Modified: 06 Jun 2022 15:39


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