Reducing the excessive inflammation after burn injury in aged mice by maintaining a healthier intestinal microbiome

Abstract One in six people are projected to be 65 years or older by 2050. As the population ages, better treatments for injuries that disproportionately impact the aged population will be needed. Clinical studies show that people aged 65 and older experience higher rates of morbidity and mortality after burn injury, including a greater incidence of pulmonary complications when compared to younger burn injured adults, which we and others believe is mediated, in part, by inflammation originating in the intestines. Herein, we use our clinically relevant model of scald burn injury in young and aged mice to determine whether cohousing aged mice with young mice or giving aged mice oral gavage of fecal material from young mice is sufficient to alter the microbiome of the aged mice and protect them from inflammation in the ileum and the lungs. Aged burn injured mice have less DNA expression of Bacteroidetes in the feces and an unhealthy Firmicutes/Bacteroidetes ratio. Both Bacteroidetes and the ratio of these two phyla are restored in aged burn injured by prior cohousing for a month with younger mice but not fecal transfer from young mice. This shift in the microbiome coincides with heightened expression of danger‐associated molecular patterns (DAMP), and pro‐inflammatory cytokine interleukin‐6 ( il6 ) in the ileum and lung of aged, burn injured mice, and heightened antimicrobial peptide camp in the lung. Cohousing reverses DAMP expression in the ileum and lung, and cathelicidin‐related antimicrobial peptide protein ( camp ) in the lung, while fecal transfer heightened DAMPs while reducing camp in the lung, and also increased IL‐6 protein in the lungs. These results highlight the importance of the intestinal microbiome in mediating inflammation within the gut–lung axis, giving insights into potential future treatments in the clinic.