Mechanisms of fasting-induced radioprotection of small intestinal epithelial cells

Project Summary We demonstrated that short-term fasting protects mice from high dose ionizing radiation by protecting small intestinal (SI) stem cells, thereby preserving SI homeostasis and promoting organismal survival. We also showed that the major ketone body produced by fasting directly modifies the epigenome of SI epithelial cells to induce gene expression changes and that fasting alters the gut microbiome to favor bacteria whose metabolites are known to induce epigenetic and gene expression changes. We will test the hypothesis that ketone bodies and microbial metabolites induced by fasting, cause epigenetic and gene expression changes in SI epithelial cells thereby providing GI radioprotection.