In rodent studies, the gut microbiota has been implicated in facilitating both 
radioresistance, by protecting the epithelium from apoptotic responses and 
radiosensitivity, inducing endothelial apoptotic responses. Despite the 
observation that large animal models, such as the Chinese Rhesus macaque and the 
Gottingen Minipig, demonstrate similarity to human physiologic responses to 
radiation, little is known about radiation-induced changes of the gut microbiome 
in these models. To compare the two models, we used bioequivalent radiation 
doses which resulted in an LD50 for Gottingen Minipigs and Chinese Rhesus 
macaques, 1.9 Gy and 6.8 Gy, respectively. Fecal samples taken prior and 3 days 
post-radiation were used for 16S rRNA gene sequence amplicon high throughput 
sequencing (Illumina MiSeq). Baseline gut microbiota profiles were dissimilar 
between minipigs and rhesus macaques. Irradiation profoundly impacted gut 
microbiota profiles in both animals. Significant increases of intracellular 
symbionts were common to both models and to reported changes in rodents 
suggesting universality of these findings post-radiation. Remarkably, opposite 
dynamics were observed for the main phyla, with increase of Firmicutes and 
decrease of Bacteroidetes and Proteobacteria in minipigs but with enrichment of 
Bacteroidetes in rhesus macaques. Minipig changes in magnitude and in variety of 
species affected were more extensive than those observed in rhesus macaques. 
This pilot study provides an important first step in comparing the 
radiosensitive pig model to the comparatively more radioresistant macaque model, 
for the identification of microbial elements which may influence 
radiosensitivity.