The gut microbiome changes in wild type and IL-18 knockout mice after 9.0 Gy total body irradiation.

Abstract

Background: Recent studies have shown that gut microbiome plays important roles in response to radiation exposure. IL-18, an inflammatory cytokine, is highly elevated in mice, mini-pigs and nonhuman primates after radiation exposure. Blocking IL-18 using its endogenous binding protein (IL-18BP) increases mice survival after radiation exposure by decreasing bone marrow interferon-gamma levels.

Methods: To further characterize the roles of IL-18 in response to radiation, both wild type and IL-18 knockout (IL-18 KO) mice were exposed to 9.0 Gy total body irradiation (TBI). The 30-day survival result demonstrated that IL-18 KO mice were significantly more resistant to radiation compared to the wild type mice (p < 0.0001). Mouse faecal samples were collected at pre-radiation (d0), d1, d3, d7, d14, d21 and d29 after radiation exposure. Microbiome profiling was performed on the faecal samples using 16S and ITS sequencing technology.

Results: Data analysis showed that there was significant difference in the bacterial microbiome between wild type and IL-18 KO mice. Cohousing of wild type and IL-18 KO mice decreased the bacterial microbiome difference between the two genotypes. Much fewer bacterial genera were significantly changed in wild type mice than the IL-18 KO mice after radiation exposure. The different composition of the IL-18 KO mice and wild type mice persisted even after radiation exposure. Bacterial genera that significantly correlated with other genera were identified in the IL-18 KO and wild type mice. The metabolic pathways that differentially expressed in both genotypes were identified. The animal bacterial microbiome data could be used to predict the animal's radiation status. The fungal microbiome had no significant difference regarding genotype or time after radiation exposure.

Conclusion: The current study helps understand the gut microbiome in different genetic backgrounds and its temporal changes after radiation exposure. Our data provide insight into the mechanisms underlying radiation-induced toxicity and help identify bacteria important in response to radiation.