Space travel is associated with continuous low-dose-rate exposure to high Linear Energy Transfer (LET) radiation. Pathophysiological manifestations after low-dose radiation exposure are strongly influenced by non-cytocidal radiation effects including microbiome and cellular gene expression. Using a mouse model for exposure to high LET radiation we observed substantial changes in the composition and functional potential of the microbiome. These were paralleled by changes in the abundance of multiple metabolites which were related to the enzymatic activity of the altered metagenome by means of metabolic network modeling. There was a complex dynamic in microbial and metabolic composition at different radiation doses suggestive of transient dose-dependent interactions between microbial ecology and signals from the host s cellular damage repair processes. Functional shifts included features associated with dysbiosis at the onset of chronic inflammatory responses which could prMouse fecal microbiome after exposure to high LET radiatione-dispose space travelers to systemic long-term health risks.