1312: SEX-SPECIFIC INTESTINAL DYSBIOSIS PERSISTS AFTER MULTICOMPARTMENTAL TRAUMATIC INJURY

Abstract

Introduction: Preclinical studies of the microbiome after severe traumatic injury have demonstrated severe dysbiosis in males, with sex-specific microbial differences up to two days after injury. However, the impact of sex on injury-driven dysbiosis over time remains unknown. We hypothesized that there would be sex-specific differences in intestinal microbial diversity and composition after traumatic injury with and without stress which would persist after seven days. Methods: Male and proestrus female Sprague-Dawley rats (n=8/group) aged 9-11 weeks were subjected to either polytrauma (PT) (lung contusion, hemorrhagic shock, cecectomy, bifemoral pseudofractures) or PT plus 2-hours daily chronic restraint stress (PT/CS) and compared to naïve. Fecal microbiome was measured on days 0, 3 and 7 using high-throughput 16S rRNA sequencing and QIIME2 bioinformatics analyses. Microbial alpha-diversity was assessed using Chao1 (number of different unique species) and Shannon (species richness and evenness) indices. Beta-diversity was assessed using principle coordinate analysis. Pairwise comparisons were performed in GraphPad and ‘R’ software package, with significance defined as p< 0.05 between males versus females. Results: PT and PT/CS reduced alpha-diversity (Chao1, Shannon) within 3-days post-intervention which persisted to day seven in both sexes; PT and PTCS females had significantly decreased Chao1 compared to male counterparts at day seven (p=0.001, p = 0.03). Beta-diversity also differed significantly between males and females by day seven within all groups (p< 0.05). At day seven, the microbial composition in PT females was dominated by Mucispirillum; whereas both PT and PT/CS males demonstrated elevated levels of Ruminococcus and Akkermansia. Conclusions: Multicompartmental trauma induces intestinal dysbiosis which is sex-specific with persistence of decreased diversity and unique ‘pathobiome’ signatures in females after one week. These findings underline sex as an important biological variable that may underlie and influence variable host-specific responses and outcomes after severe trauma and critical illness, thereby underscoring the need to consider precision medicine strategies to ameliorate these outcomes.