Maintenance of the commensal bacteria that comprise the gut microbiome is 
essential to both gut and systemic health. Traumatic injury, such as burn, 
elicits a number of changes in the gut, including a shift in the composition of 
the microbiome (dysbiosis), increased gut leakiness, and bacterial translocation 
into the lymphatic system and bloodstream. These effects are believed to 
contribute to devastating secondary complications following burn, including 
pneumonia, acute respiratory distress syndrome, multi-organ failure, and septic 
shock. Clinical studies demonstrate that advanced age causes a significant 
increase in mortality following burn, but the role of the gut in this 
age-dependent susceptibility has not been investigated. In this study, we 
combined our well-established murine model of scald burn injury with bacterial 
16S-rRNA gene sequencing to investigate how burn injury affects the fecal 
microbiome in aged versus young mice. Of our treatment groups, the most 
substantial shift in gut microbial populations was observed in aged mice that 
underwent burn injury. We then profiled antimicrobial peptides (AMPs) in the 
ileum, and found that burn injury stimulated a 20-fold rise in levels of 
regenerating islet-derived protein 3 gamma (Reg3γ), a 16-fold rise in 
regenerating islet-derived protein 3 beta (Reg3β), and an 8-fold rise in 
Cathelicidin-related antimicrobial peptide (Cramp) in young, but not aged mice. 
Advanced age alone elicited 5-fold higher levels of alpha defensin-related 
sequence1 (Defa-rs1) in the ileum, but this increase was lost following burn. 
Comparison of bacterial genera abundance and AMP expression across treatment 
groups revealed distinct correlation patterns between AMPs and individual 
genera. Our results reveal that burn injury drives microbiome dysbiosis and 
altered AMP expression in an age-dependent fashion, and highlight potential 
mechanistic targets contributing to the increased morbidity and mortality 
observed in elderly burn patients.