Targeted Metabolomics Reveals Metabolomic Signatures Correlating Gastrointestinal Tissue to Plasma in a Mouse Total-body Irradiation Model

High-throughput, targeted metabolomics was used to identify early time point small intestine and plasma metabolite markers of gastrointestinal acute radiation syndrome. The small intestine metabolite markers were cross-correlated to plasma metabolites in order to identify minimally invasive circulating markers. The radiation exposure covered lethal and sub-lethal gastrointestinal acute radiation syndrome. The small intestine and plasma metabolite profiles were generated at 1 and 3 days post-exposure following total-body irradiation. The small intestine and plasma metabolite profiles for mice receiving radiation at day 1 and 3 post-exposure were significantly different from sham-irradiated mice. There were 14 metabolite markers identified at day 1 and 18 metabolite markers at day 3 that were small intestine-specific plasma markers of gastrointestinal acute radiation syndrome. A number of the identified metabolites at day 1 were amino acids. Dysregulation of amino acid metabolism at 24-hours post total-body irradiation provides potential insight into the initial inflammatory response during gastrointestinal acute radiation syndrome.