Department of Surgery and Sepsis and Critical Illness Research Center, University of Florida College of Medicine, Gainesville, Florida.
The Gut Biome Lab, Department of Health, Nutrition, and Food Sciences, Florida State University College of Education, Health, and Human Sciences, Tallahassee, Florida.
Shock. 2024 Dec 1;62(6):762-771. doi: 10.1097/SHK.0000000000002428. Epub 2024 Aug 8.
Background : Previous preclinical studies have demonstrated a pathobiome after traumatic injury; however, the impact of postinjury sepsis on gut epithelial permeability and bacterial translocation remains unknown. We hypothesized that polytrauma with postinjury pneumonia would result in impaired gut permeability leading to specific blood microbiome arrays. Methods : Male and proestrus female Sprague-Dawley rats were subjected to either polytrauma (PT), PT plus 2-hours daily chronic restraint stress (PT/CS), PT with postinjury day 1 inoculation with pseudomonas pneumonia (PT + PNA), PT/CS + PNA, or naive controls. Whole blood microbiome was measured serially using high-throughput 16S rRNA sequencing and QIIME2 bioinformatics analyses. Microbial diversity was assessed using Chao1/Shannon indices and principle coordinate analysis. Intestinal permeability was evaluated by plasma occludin and lipopolysaccharide-binding protein assays. Results : PT/CS + PNA had increased intestinal permeability compared to uninfected counterparts (PT/CS) with significantly elevated occludin ( P < 0.01). Bacteria was not detected in the blood of naïve controls, PT or PT/CS, but was present in both PT + PNA and PT/CS + PNA on days 2 and 7. The PT/CS + PNA blood biome showed dominance of Streptococcus compared to PT + PNA at day 2 ( P < 0.05). Females PT/CS + PNA had a significant abundance of Staphylococcus at day 2 and Streptococcus at day 7 in the blood biome compared to male counterparts ( P < 0.05). Conclusion : Multicompartmental trauma with postinjury pneumonia results in increased intestinal permeability and bacteremia with a unique blood biome, with sexual dimorphisms evident in the blood biome composition. These findings suggest that postinjury sepsis has clinical significance and could influence outcomes after severe trauma and critical illness.
先前的临床前研究表明,创伤后存在一种病理生物群;然而,创伤后脓毒症对肠道上皮通透性和细菌易位的影响尚不清楚。我们假设,创伤后并发肺炎的多器官创伤会导致肠道通透性受损,从而导致特定的血液微生物组谱发生变化。方法:雄性和动情前期雌性 Sprague-Dawley 大鼠分别接受多器官创伤(PT)、PT 加每日 2 小时慢性束缚应激(PT/CS)、PT 后第 1 天接种铜绿假单胞菌肺炎(PT + PNA)、PT/CS + PNA 或假手术对照。使用高通量 16S rRNA 测序和 QIIME2 生物信息学分析连续测量全血微生物组。使用 Chao1/Shannon 指数和主坐标分析评估微生物多样性。通过测定血浆 occludin 和脂多糖结合蛋白评估肠道通透性。结果:PT/CS + PNA 与未感染对照(PT/CS)相比,肠道通透性增加,occludin 显著升高(P < 0.01)。在未感染对照、PT 或 PT/CS 大鼠的血液中均未检测到细菌,但在 PT + PNA 和 PT/CS + PNA 大鼠的血液中,在第 2 天和第 7 天均有细菌存在。与 PT + PNA 相比,PT/CS + PNA 大鼠的血液微生物组在第 2 天以链球菌为主(P < 0.05)。与雄性大鼠相比,PT/CS + PNA 雌性大鼠的血液微生物组在第 2 天具有显著丰富的葡萄球菌,在第 7 天具有显著丰富的链球菌(P < 0.05)。结论:创伤后继发肺炎的多器官创伤导致肠道通透性增加和菌血症,并伴有独特的血液微生物组,血液微生物组组成存在明显的性别差异。这些发现表明,创伤后脓毒症具有临床意义,并可能影响严重创伤和危重病患者的预后。