Fecal Microbiota Transplant Restores Mucosal Integrity in a Murine Model of Burn Injury

Abstract

The gut microbiome is a community of commensal organisms that are known to play a role in nutrient production as well as gut homeostasis. The composition of the gut flora can be affected by many factors; however, the impact of burn injury on the microbiome is not fully known. Here, we hypothesized that burn-induced changes to the microbiome would impact overall colon health. After scald-burn injury, cecal samples were analyzed for aerobic and anaerobic colony forming units, bacterial community, and butyrate levels. In addition, colon and total intestinal permeabilities were determined. These parameters were further determined in a germ-reduced murine model. Following both burn injury and germ reduction, we observed decreases in aerobic and anaerobic bacteria, increased colon permeability and no change to small intestinal permeability. After burn injury, we further observed a significant decrease in the butyrate producing bacteria R. Gnavus, C. Eutactus, and Roseburia species as well as decreases in colonic butyrate. Finally, in mice that underwent burn followed by fecal microbiota transplant, bacteria levels and mucosal integrity were restored. Altogether our data demonstrate that burn injury can alter the microbiome leading to decreased butyrate levels and increased colon permeability. Of interest, fecal microbiota transplant treatment was able to ameliorate the burn-induced changes in colon permeability. Thus, fecal transplantation may represent a novel therapy in restoring colon health after burn injury.

Burn injury influences the T cell homeostasis in a butyrate-acid sphingomyelinase dependent manner

“…Specifically, significant reductions were observed in the butyrate producing species, gnavus and eutactus . Consistent with the reductions in butyrate-producing bacteria following [20], we demonstrate that colonic butyrate levels are significantly reduced after burn injury.…”

“…Earley et al demonstrate burn injury induces a dramatic dysbiosis of the intestinal microbiome in humans and mice and suggest that potential mechanisms for the shifts in bacterial communities is increased intestinal inflammation and reduction in antimicrobial peptides [19]. Similarly, Kuethe et al, demonstrate alterations in intestinal microbiota and colonic permeability [20]. Specifically, significant reductions were observed in the butyrate producing species, gnavus and eutactus .…”

“…Taken a step further, a recent clinical study examined the fecal material from patients with systemic inflammatory response syndrome, due to infection, trauma, or burn, and demonstrated a loss of anaerobes and reduction in organic acids [18]. Further, burn injury has been shown to induce a dysbiosis of the intestinal microbiome, increase intestinal permeability and increase bacterial translocation [19, 20], suggesting that the gut may be a potential source of bacterial infection. While it is known that trauma and burn injury alter the gut microbiota, it is unknown how these changes affect immune responsiveness.…”

“…Specifically, members from the Firmicute phylum and the Clostridiale family produce butyrate [31], a crucial SCFA for immune system regulation. We previously demonstrated that burn injury significantly reduces the Firmicute phylum, in particular the gnavus and eutactus species, both known butyrate producers [20], particularly on post burn day (PBD) 6. As it is known that the microbiota and Asm system are altered following burn injury, it is unknown how butyrate, may impact Asm activity.…”

The Use of Microbiome Restoration Therapeutics to Eliminate Intestinal Colonization With Multidrug-Resistant Organisms

“…45 A mouse model suggests that burn injury may also lead to dysbiosis as it was found to decrease aerobic and anaerobic species in a manner similar to antibiotic therapy. 46 …”