The development of effective biomarkers for detecting the magnitude of radiation 
exposure and resiliency of host response is crucial to identifying appropriate 
treatment strategies after radiation exposure. We hypothesized that the 
gastrointestinal resident bacteria would demonstrate predictable, dose-dependent 
changes after radiation exposure across two large animal models of acute 
radiation syndrome. Here, Göttingen minipigs (GMP) (n = 50) and rhesus macaques 
(n = 48) were exposed to five dose levels (resulting in mortality rates of 
33-100% and 25-68.7%, respectively). Fecal samples taken prior to and after 
irradiation (day 0 for GMP; day 0, 3 and 14 for macaques) were used for 16S rRNA 
gene sequence amplicon high-throughput sequencing. Baseline gut microbiota 
profiles were dissimilar between GMP and macaques, however, radiation appeared 
to have similar effect at the phylum level, resulting in Bacteroidetes decrease 
and Firmicutes increase in both models. The abundance of the main Bacteroidetes 
genus ( Bacteroides for GMP, Prevotella for macaques) was profoundly decreased 
by irradiation. Intracellular symbionts [Elusimicrobia in GMP, Treponema 
(Spirochaetes) in macaques] consistently increased after irradiation, suggesting 
their use as potential biomarkers of intestinal injury, and potential negative 
effect on health. Prevotella, Lactobacillus, Clostridium XIVa, Oscillibacter and 
Elusimicrobium/ Treponema abundances were found to be very significantly 
correlated with radiation intensity. Furthermore, Prevotella, Enterorhabdus and 
Ruminococcus and Enterorhabdus maintenance was strongly associated with survival 
in GMP, while Prevotella, Oscillibacter and Treponema were strongly associated 
with survival and Streptococcus with death in macaques. Overall, we found that a 
wide range of gut bacterial genera known to be abundant in the human gut 
microbiota are excellent biomarkers of radiation intensity and resilience in 
animal models, and that detrimental effects can be monitored, and potentially 
prevented, by targeting selected genera.