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Citation
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Munley JA, Kelly LS, Pons EE, Kannan KB, Coldwell PS, Whitley EM, Gillies GS, Efron PA, Nagpal R, Mohr AM. J. Trauma Acute Care Surg. 2022; ePub(ePub): ePub. |
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Abstract
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BACKGROUND: Previous animal models have demonstrated altered gut microbiome after mild traumatic injury; however, the impact of injury severity and critical illness is unknown. We hypothesized that a rodent model of severe multicompartmental injuries and chronic stress would demonstrate microbiome alterations toward a "pathobiome" characterized by an overabundance of pathogenic organisms which would persist one week after injury.
METHODS: Male Sprague-Dawley rats (n = 8/group) were subjected to either polytrauma (PT) (lung contusion, hemorrhagic shock, cecectomy, and bifemoral pseudofractures), PT plus 2-hours daily chronic restraint stress (PT/CS), or naïve controls. Fecal microbiome was measured on days 0, 3, and 7 using high-throughput 16S rRNA sequencing and QIIME2 bioinformatics analysis. Microbial alpha-diversity was assessed using Chao1 and Shannon indices and beta-diversity with principle coordinate analysis. Intestinal permeability was evaluated by plasma occludin; ileum and descending colon tissues were reviewed for injury. Analyses were performed in GraphPad and R, with significance defined as p < 0.05.
RESULTS: There were significant alterations in beta-diversity at day 3 and between all groups. By day 3, both PT and PT/CS demonstrated significantly depleted bacterial diversity (Chao1) (p = 0.01, p = 0.001 respectively) versus naïve, which persisted up to day 7 in PT/CS only (p = 0.001). Anaerostipes and Rothia dominated PT and Lactobacillus bloomed in PT/CS cohorts by day 7. Plasma occludin was significantly elevated in PT/CS compared to naïve (p = 0.04) and descending colon of both PT and PT/CS showed significantly higher injury compared to naïve (p = 0.005, p = 0.006).
CONCLUSIONS: Polytrauma with and without chronic stress induces significant alterations in microbiome diversity and composition within three days; these changes are more prominent and persist for one-week post-injury with stress. This rapid and persistent transition to a "pathobiome" phenotype represents a critical phenomenon that may influence outcomes after severe trauma and critical illness. LEVEL OF EVIDENCE: Not applicable - basic science.
Language: en |