Circulating Metabolic Changes Accompanying Intestinal Injury After Total-Body Irradiation in Mice

Background: Early circulating metabolic indicators of radiation-induced intestinal injury remain to be explored. Methods: Male C57BL/6J mice received 0, 6, 8, 10, 12, or 14 Gy total-body irradiation. The study integrated 30-day survival monitoring, intestinal histological assessment, and targeted plasma metabolomics on days 1, 3, and 7 after irradiation, together with intestinal biochemical measurements and analysis of publicly available single-cell transcriptomic datasets. Results: Mortality increased sharply between 8 and 10 Gy, accompanied by progressive crypt–villus injury. Both plasma and intestinal tissue 5-hydroxylysine levels increased at lower doses but decreased at higher doses. Plasma hydroxyproline and citrulline levels decreased, while intestinal urea was reduced at high doses despite stable plasma urea concentrations. Plasma serotonin increased during the early phase after irradiation. Single-cell analysis provided cellular context for collagen hydroxylation, nitrogen metabolism, and the tryptophan–serotonin metabolic pathway. Conclusions: Circulating amino acids and related metabolites exhibited dose- and time-dependent alterations that were synchronous with the progression of intestinal radiation injury, providing preliminary evidence for further exploration of candidate indicators for early injury assessment.