Release of Interferon-β (IFN-β) from Probiotic Limosilactobacillus reuteri-IFN-β (LR-IFN-β) Mitigates Gastrointestinal Acute Radiation Syndrome (GI-ARS) following Whole Abdominal Irradiation

Abstract

Irradiation can be an effective treatment for ovarian cancer, but its use is limited by intestinal toxicity. Thus, strategies to mitigate toxicity are important and can revitalize the current standard of care. We previously established that LR-IL-22 protects the intestine from WAI. We now hypothesize that LR-IFN-β is an effective radiation protector and mitigator and is rapidly cleared from the digestive tract, making it an option for intestinal radioprotection. We report that the gavage of LR-IFN-β during WAI provides improved intestinal barrier integrity and significantly preserves the numbers of Lgr5+GFP+ intestinal stem cells, improving survival. The rapid clearance of the genetically engineered probiotic from the digestive tract renders it a safe and feasible radiation mitigator. Therefore, the above genetically engineered probiotic is both a feasible and effective radiation mitigator that could potentially revolutionize the management of OC patients. Furthermore, the subsequent addition of platinum/taxane-based chemotherapy to the combination of WAI and LR-IFN-β should reduce tumor volume while protecting the intestine and should improve the overall survival in OC patients.

Human adipose ECM alleviates radiation-induced skin fibrosis via endothelial cell-mediated M2 macrophage polarization

“… 59 Fresh frozen skin tissue were processed as explained. 60 Samples were diluted 2-fold by adding 75μl supernatant to 75 μl of Calibrator Diluent mix (Kit). Add 50 μl sample or standard (Kit) to 96 well plates according to the assay scheme.…”

Advanced Technologies in Radiation Research

“…A single oral dose of L. reuteri engineered to release interleukin-22, a known radiation mitigator, significantly improved the survival of mice exposed to 9.25 Gy total-body irradiation (85,86). Moreover, interferon-b released through L. reuteri delivery also demonstrated a protective effect in mice exposed to total-body irradiation, whole-abdomen irradiation and partial-body irradiation (87). Due to the ultimate goal of human use, further safety considerations need to be investigated before the L. reuteri delivery system can be tested in larger models of irradiation.…”