{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T17:30:15Z","timestamp":1787592615010,"version":"build-2736575974"},"reference-count":40,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T00:00:00Z","timestamp":1652745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"NIAID\/NIH","doi-asserted-by":"publisher","award":["U19-AI068021"],"award-info":[{"award-number":["U19-AI068021"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIAID\/NIH","doi-asserted-by":"publisher","award":["P30CA047904"],"award-info":[{"award-number":["P30CA047904"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Hillman Cancer Animal Faiclity and the Flow Cytometry Cener","award":["U19-AI068021"],"award-info":[{"award-number":["U19-AI068021"]}]},{"name":"The Hillman Cancer Animal Faiclity and the Flow Cytometry Cener","award":["P30CA047904"],"award-info":[{"award-number":["P30CA047904"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>(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.<\/jats:p>","DOI":"10.3390\/ijms23105616","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T08:34:29Z","timestamp":1652776469000},"page":"5616","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Intestinal Radiation Protection and Mitigation by Second-Generation Probiotic Lactobacillus-reuteri Engineered to Deliver Interleukin-22"],"prefix":"10.3390","volume":"23","author":[{"given":"Alexis","family":"Espinal","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Epperly","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5603-5147","authenticated-orcid":false,"given":"Amitava","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Shields","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Saiful","family":"Huq","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diala Fatima","family":"Hamade","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anda M.","family":"Vlad","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Coffman","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Buckanovich","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4021-1000","authenticated-orcid":false,"given":"Jian","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Leibowitz","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Peter","family":"van Pijkeren","sequence":"additional","affiliation":[{"name":"Department of Food Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi B.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Stolz","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Watkins","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asim","family":"Ejaz","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, University of Pittsburgh, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2271-7566","authenticated-orcid":false,"given":"Joel S.","family":"Greenberger","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3494","DOI":"10.1038\/ncomms4494","article-title":"Ionizing irradiation induces acute haematopoietic syndrome and gastrointestinal syndrome independently in mice","volume":"5","author":"Leibowitz","year":"2014","journal-title":"Nat. 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