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

Abstract

(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.

Modes of therapeutic delivery in synthetic microbiology

“…This approach has proven successful in different preclinical disease models. Delivery of murine IL-22 by L. reuteri via phage-mediated lysis ameliorated alcohol-induced liver disease in ethanol-binge-fed mice and increased the survival of mice exposed to total body irradiation [ 51 , 52 , 54 , 55 ].…”

Pathogenesis and therapy of radiation enteritis with gut microbiota

“…In addition to probiotics and fecal bacteria transplantation, drugs can also be combined with probiotics. For example, gavage Lactobacillus reuteri as a platform for the second-generation probiotic Lactobacillusreuteri-Interleukin-22 (LR-IL-22) improved delivery of IL-22 to the irradiated intestine, and effectively reduced the intestinal damage caused by irradiated intestinal tract (Espinal et al, 2022).…”

Simulate the Dynamic Interactions Across Nutritional Supplements, the Polybiome, and the Biochemical Approach Dependent on Patient-Derived Gastrointestinal Knowledge

“…With these novel discoveries, gastro-intestinal patient-derived RNA presents a unique biological method for examining the sensory information provided by the gastro-intestinal commensal RNA biome. It is easier to study how biologically active substances affect the intestinal mucosa than it is to find bacteria [184]. In order to simulate a real-world scenario, it is important to introduce bacteria into the spheroid lumen and, if at all feasible, complex combinations of microbial populations.…”