Burn Injury Alters the Intestinal Microbiota and Increases Inflammation and Risk of Sepsis

Burn patients suffer a global immune response characterized by a breakdown of the epithelial barrier in the gut, inflammation, and increased bacterial translocation leading to an increased susceptibility to systemic septic infections. Interestingly, it is not known how the diversity of the intestinal microbiota changes following thermal injury and its implications in inflammation and infection. Male C57BL/6 mice were subjected to a ~20% total body surface area burn or sham burn and sacrificed on days 1, 3 and 5 thereafter. Intestinal transit and permeability was measured with the dye FITC-dextran. DNA and RNA were purified from the distal small intestine tissue and feces and the large intestine tissue and feces, and subjected to qPCR to measure gene expression of anti-microbial peptides (AMPs) and copy number of the 16s bacterial gene. A Multiplex assay was performed on homogenized intestine tissue to measure cytokines levels. A significant decrease in intestinal transit and an increase in intestinal permeability one day after burn injury relative to sham (p<.05) was measured. QPCR analysis of the DNA isolated from the small intestine showed that burn increased copy number of total bacteria ~20 fold, while also significantly increasing and deceasing specific bacterial groups. In addition, AMPs showed a 50% decrease in α-defensins with a 50-60% decrease in the c-type lectins and lactoferrin, respectively (p<.05). Furthermore, a significant increase in a number of pro-inflammatory cytokines in the intestine of the burned mice were seen (IL-6, -13, -31,-33,G-CSF, KC, MCP-1, p<.05). Preliminary results of the DNA isolated from the large intestine suggest the same trends seen in the small intestine. These results suggest that burn injury decreases intestinal transit, attenuates the expression of AMPs, and promotes a dysregulation of the gut microbiota. This suggests that the altered gut microbiota after burn injury leads to bacterial translocation and inflammation. Thus, the gut microbiota may play a role in post burn inflammation and sepsis.