Remote burn injury in aged mice induces colonic lymphoid aggregate expansion and dysbiosis of the fecal microbiome which correlates with neuroinflammation.

The Earth's population is aging and, by 2050, 1 out of 6 people will be 65 or older. Therefore, proper treatment of injuries that disproportionately impact people of advanced age will be more important. Clinical studies reveal people aged ≥65 account for 16.5% of all burn injuries, and experience higher morbidity, including neurocognitive decline, and mortality that we and others believe are mediated, in part, by heightened intestinal permeability. Herein we used our clinically relevant model of scald burn injury in young and aged mice to determine whether age and burn injury cooperate to induce heightened colonic damage, alterations to the fecal microbiome, and whether resultant changes in the microbiome correlate with neuroinflammation. We found that aged, burn injured mice have an increase in colonic lymphoid aggregates, inflammation, and pro-inflammatory chemokine expression when compared to young groups and sham injured aged mice. We then performed fecal microbiota sequencing and found a striking reduction in gut protective bacterial taxa, including Akkermansia, in the aged burn group compared to all other groups. This reduction correlated with an increase in serum FITC-dextran administered by gavage, indicating heightened intestinal permeability. Further, loss of Akkermansia was highly correlated with increased mRNA expression of neuroinflammatory markers in the brain, including ccl2, tnfa, cxcl1, and s100a8. Finally, we discovered that post-burn alterations in the microbiome correlated with measures of strength in all treatment groups, and those that performed better on the rotarod and hanging wire tests had higher abundance of Akkermansia than those that performed worse. Taken together, these findings indicate that loss of protective bacteria after burn injury in aged mice contributes to alterations in the colon, gut leakiness, neuroinflammation, and strength. Therefore, supplementation of protective bacteria, such as Akkermansia, after burn injury in aged patients may have therapeutic benefit.