A PROSPECTIVE STUDY IN SEVERELY INJURED PATIENTS REVEALS AN ALTERED GUT MICROBIOME IS ASSOCIATED WITH TRANSFUSION VOLUME

Susannah E. Nicholson, David M. Burmeister, Taylor R. Johnson, Yi Zou, Zhao Lai, Shannon Scroggins, Mark DeRosa, Rachelle B. Jonas, Daniel R. Merrill, Caroline Zhu, Larry M. Newton, Ronald M. Stewart, Martin G. Schwacha, Donald H. Jenkins, Brian J. Eastridge

Traumatic injury can lead to a compromised intestinal epithelial barrier and inflammation. While alterations in the gut microbiome of critically injured patients may influence clinical outcomes, the impact of trauma on gut microbial composition is unknown. Our objective was to determine if the gut microbiome is altered in severely injured patients and begin to characterize changes in the gut microbiome due to time and therapeutic intervention. We conducted a prospective, observational study in adult patients (n=72) sustaining severe injury admitted to a Level I Trauma Center. Healthy volunteers (n=13) were also examined. Fecal specimens were collected on admission to the Emergency Department (ED) and at 3, 7, 10, and 13 (±2) days following injury. Microbial DNA was isolated for 16s rRNA sequencing, and α- and β-diversity were estimated, according to taxonomic classification against the Greengenes database. The gut microbiome of trauma patients was altered on admission (i.e., within 30 minutes following injury) compared to healthy volunteers. Patients with an unchanged gut microbiome on admission were transfused more RBCs than those with an altered gut microbiome (p<0.001). Although the gut microbiome started to return to a β-diversity profile similar to that of healthy volunteers over time, it remained different from healthy controls. Alternatively, α-diversity initially increased post-injury, but subsequently decreased during the hospitalization. Injured patients on admission had a decreased abundance of traditionally beneficial microbial phyla (e.g., Firmicutes) with a concomitant decrease in opportunistic phyla (e.g., Proteobacteria) compared to healthy controls (p< 0.05). Large amounts of blood products and RBCs were both associated with higher α-diversity (p<0.001) and a β-diversity clustering closer to healthy controls. The human gut microbiome changes early after trauma and may be aided by early massive transfusion. Ultimately, the gut microbiome of trauma patients may provide valuable diagnostic and therapeutic insight for the improvement of outcomes post-injury. Level III STUDY TYPE: Prognostic and Epidemiological.