RNA-Seq of IEC-6 cells after L-citrulline treatment
The widespread use of nuclear technology increasing the risk of external radiation and internal radiation exposure. The intestine tract is known to be particularly sensitive to the ionizing radiation. However, in contrast to external irradiation, less is known about the biological effects of internal radiation exposure and its countermeasures. In this study, we utilized Yttrium-90 (Y90) carbon microsphere-based gavage (0 - 5.0 mCi) to establish an internal radiation exposure model. Following administration, the mice exhibited intestinal damage as a result of the internal radiation exposure. Through multi-omics high-throughput analysis, we found that the exposure to internal radiation resulted in a significant impact on the gut microbiota, fecal metabolites, colonic metabolites and mRNA expression profiles in colon tissues. The concentrations of 7 metabolites simultaneously changed in fecal and colon tissues, including saccharopine, aconitic acid, L-cysteine-glycine, dodecanol, lignoceric acid, resveratrol and L-citrulline. We further investigated the biological effect of L-citrulline. L-citrulline exerted a protective effect on intestinal epithelial cells by reducing the production of ROS and cellular apoptosis. And metabolite pathway enrichment analysis (MPEA) showed L-citrulline is a co-metabolite of host and microbiota (mainly from Firmicutes and Bacteroidota). Furthermore, we indicated that treatment with L-citrulline increased the citrullination modification of histone H3. Chip-Seq and RNA-Seq showed xxx regulates the citrullination of histone H3. Taken together, this study reveals the potential of L-citrulline as a radiation protection agent against internal radiation exposure, suggesting the possibility that metabolites play a key role in the regulation of injury after radiation challenge.