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. 2024 Jul 1;97(1):65-72.
doi: 10.1097/TA.0000000000004300. Epub 2024 Mar 14.

Acute emergence of the intestinal pathobiome after postinjury pneumonia

Jennifer A Munley  1 , Lauren S Kelly, Gwoncheol Park, Stacey K Drury, Gwendolyn S Gillies, Preston S Coldwell, Kolenkode B Kannan, Letitia E Bible, Philip A Efron, Ravinder Nagpal, Alicia M Mohr
Affiliations

Acute emergence of the intestinal pathobiome after postinjury pneumonia

Jennifer A Munley et al. J Trauma Acute Care Surg. .

Abstract

Background: Previous preclinical studies have demonstrated sex-specific alterations in the gut microbiome following traumatic injury or sepsis alone; however, the impact of host sex on dysbiosis in the setting of postinjury sepsis acutely is unknown. We hypothesized that multicompartmental injury with subsequent pneumonia would result in host sex-specific dysbiosis.

Methods: Male and proestrus female Sprague-Dawley rats (n = 8/group) were subjected to either multicompartmental trauma (PT) (lung contusion, hemorrhagic shock, cecectomy, bifemoral pseudofracture), PT plus 2-hour daily restraint stress (PT/RS), PT with postinjury day 1 Pseudomonas aeruginosa pneumonia (PT-PNA), PT/RS with pneumonia (PT/RS-PNA), or naive controls. Fecal microbiome was measured on days 0 and 2 using high-throughput 16S rRNA sequencing and Quantitative Insights Into Microbial Ecology 2 bioinformatics analyses. Microbial α-diversity was assessed using Chao1 (number of different unique species) and Shannon (species richness and evenness) indices. β-diversity was assessed using principal coordinate analysis. Significance was defined as p < 0.05.

Results: All groups had drastic declines in the Chao1 (α-diversity) index compared with naive controls ( p < 0.05). Groups PT-PNA and PT/RS-PNA resulted in different β-diversity arrays compared with uninfected counterparts (PT, PT/RS) ( p = 0.001). Postinjury sepsis cohorts showed a loss of commensal bacteria along with emergence of pathogenic bacteria, with blooms of Proteus in PT-PNA and Escherichia-Shigella group in PT/RS-PNA compared with other cohorts. At day 2, PT-PNA resulted in β-diversity, which was unique between males and females ( p = 0.004). Microbiome composition in PT-PNA males was dominated by Anaerostipes and Parasuterella , whereas females had increased Barnesiella and Oscillibacter . The PT/RS males had an abundance of Gastranaerophilales and Muribaculaceae .

Conclusion: Multicompartmental trauma complicated by sepsis significantly diminishes diversity and alters microbial composition toward a severely dysbiotic state early after injury, which varies between males and females. These findings highlight the role of sex in postinjury sepsis and the pathobiome, which may influence outcomes after severe trauma and sepsis.

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Conflict of interest statement

The authors declare no conflicts of interest. This research was supported by the National Institutes of Health. AMM was supported by NIH NIGMS R01 GM105893. JAM, LSK, and SLK were supported by postgraduate training grant NIH NIGMS T32 GM-008721 in burns, trauma, and perioperative injury. GSG was supported by postgraduate training grant NIH NHLBI T32 HL-160491 interdisciplinary training for vascular surgeon scientists. All conflicts of interest disclosure forms for the Journal of Trauma and Acute Care Surgery have been submitted.

Figures

Figure 1.
Figure 1.
Changes in alpha-diversity represented by the (A) Chao1 index at day 2; and (B) Shannon index at day 2; *p<0.05 versus naïve. PT - polytrauma; PT/RS - polytrauma/restraint stress; PT+PNA - polytrauma with pneumonia; PT/RS+PNA - polytrauma with restraint stress and pneumonia.
Figure 2.
Figure 2.
(A) Principal coordinate analysis (PCoA) plot showing changes in beta-diversity, the measure of differences in biodiversity across cohorts at day 2; percent on each orthogonal axis represents the proportion of overall variance in the data. (B) Genus-level microbiome composition between cohorts at day 2; unique microbial species identified with *p<0.01. PT - polytrauma; PT/RS - polytrauma/restraint stress; PT+PNA – polytrauma with pneumonia; PT/RS+PNA – polytrauma with restraint stress and pneumonia. Dashed lines depict a representative sampling of the group.
Figure 3.
Figure 3.
Changes in the microbiome within the polytrauma with pneumonia (PT+PNA) cohort over time. (A) Chao1 index; (B) Shannon index; and (C) principal coordinate analysis (PCoA) plot showing changes in beta-diversity, the measure of differences in biodiversity (percent on each orthogonal axis represents the proportion of overall variance in the data), and D) genus-level microbiome composition with unique microbial species identified with *p<0.01.
Figure 4.
Figure 4.
Changes in the microbiome within the polytrauma with restraint stress and pneumonia (PT/RS+PNA) cohort over time. (A) Chao1 index; (B) Shannon index; (C) principal coordinate analysis (PCoA) plot showing changes in beta-diversity, the measure of differences in biodiversity (percent on each orthogonal axis represents the proportion of overall variance in the data); and (D) genus-level microbiome composition with unique microbial species identified with *p<0.01.
Figure 5.
Figure 5.
Principal coordinate analysis (PCoA) plots showing changes in beta-diversity, the measure of differences in biodiversity (percent on each orthogonal axis represents the proportion of overall variance in the data) between males and females at day 2 within A) PT+PNA and B) PT/RS+PNA cohorts. PT+PNA - polytrauma with pneumonia; PT/RS+PNA - polytrauma with restraint stress and pneumonia.
Figure 6.
Figure 6.
Genus-level microbiome composition between males and females at day 2 within A) PT+PNA and B) PT/RS+PNA cohorts. Unique microbial species identified with *p<0.01. PT+PNA - polytrauma with pneumonia; PT/RS+PNA - polytrauma with restraint stress and pneumonia.
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References

    1. Belkaid Y, Harrison OJ. Homeostatic Immunity and the Microbiota. Immunity. 2017;46(4):562–76. - PMC - PubMed
    1. Munley JA, Kirkpatrick SL, Gillies GS, Bible LE, Efron PA, Nagpal R, et al. The Intestinal Microbiome after Traumatic Injury. Microorganisms. 2023;11(8). - PMC - PubMed
    1. Miller WD, Keskey R, Alverdy JC. Sepsis and the Microbiome: A Vicious Cycle. J Infect Dis. 2021;223(12 Suppl 2):S264–S9. - PMC - PubMed
    1. Haak BW, Wiersinga WJ. The role of the gut microbiota in sepsis. Lancet Gastroenterol Hepatol. 2017;2(2):135–43. - PubMed
    1. Krezalek MA, DeFazio J, Zaborina O, Zaborin A, Alverdy JC. The Shift of an Intestinal “Microbiome” to a “Pathobiome” Governs the Course and Outcome of Sepsis Following Surgical Injury. Shock. 2016;45(5):475–82. - PMC - PubMed

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