• Timothy S Horseman, Babita Parajuli, Andrew M Frank, Alia Weaver, David A Schauer, Sean Moran, Joseph A Anderson, Gregory P Holmes-Hampton, and David M Burmeister.
• Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
• Shock. 2024 Oct 1; 62 (4): 556564556-564.

AbstractBoth abdominal radiotherapy and a nuclear event can result in gastrointestinal symptoms, including acute radiation syndrome (GI-ARS). GI-ARS is characterized by compromised intestinal barrier integrity increasing the risk for infectious complications. Physiologically relevant animal models are crucial for elucidating host responses and therapeutic targets. We aimed to determine the radiation dose requirements for creating GI-ARS in the Sinclair minipig. Male, sexually mature swine were randomly divided into sham (n = 6) and three lower hemibody radiation dosage groups of 8, 10, and 12 Gy (n = 5/group) delivered using linear accelerator-derived x-rays (1.9 Gy/min). Animals were monitored for GI-ARS symptoms for 14 days with rectal swab and blood collection at days 0-3, 7, 10, and 14 followed by necropsy for western blotting and histology. Dose-dependent increases in weight loss, diarrhea severity, and mortality (log-rank test, P = 0.041) were seen. Villi length was significantly reduced in all irradiated animals compared to controls ( P < 0.001). Serum citrulline decreased and bacterial translocation increased after irradiation compared to controls. Increased NLRP3 levels in post-mortem jejunum were seen ( P = 0.0043) as well as increased IL-1β levels in the 12 Gy group ( P = 0.041). Radiation dose and survival were associated with significant gut microbial community shifts in beta diversity. Moreover, decedents had increased Porphyromonas, Campylobacter, Bacteroides , Parvimonas , and decreased Fusobacterium and decreased Aerococcus, Lactobacillus, Prevotella, and Streptococcus . Our novel Sinclair minipig model showed dose-dependent clinical symptoms of GI-ARS. These findings provide invaluable insights into the intricate interplay between GI-ARS, intestinal inflammation, and gut microbiota alterations offering potential targets for therapeutic and diagnostic interventions after radiation exposure.Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government"œ for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.

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