Multi-omics analyses of radiation survivors identify radioprotective microbes and metabolites

Abstract Ionizing-radiation causes acute radiation syndrome leading to hematopoietic, gastrointestinal and cerebrovascular injuries. Substantial federal efforts have been made develop therapeutic radioprotectants for routine clinical use, however it remains a long-standing unresolved problem. We investigated population of mice that recovered from high-dose live normal lifespans. These elite-survivors harbored distinct gut microbiota developed post-radiation protected against radiation-induced damage death in germ-free conventionally housed recipients. Elevated abundances members the bacterial taxa Lachnospiraceae Enterococcaceae were associated with restoration hematopoiesis repair. bacteria also found be more abundant leukemia patients undergoing radiotherapy who displayed milder dysfunction. Metabolomics revealed increased fecal concentrations microbially derived propionate tryptophan metabolites elite-survivors. The these correlated long-term radioprotection, mitigation hematopoietic syndromes, reduction pro-inflammatory responses. novelty our work lies first identification downstream providing protection lethal radiation. Furthermore, provides comprehensive omics dataset at metabolite levels is broad interest serves as powerful resource example actionable targets microbiome studies.