Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Dec;174(6):1453-1462.
doi: 10.1016/j.surg.2023.08.023. Epub 2023 Oct 11.

Sex-specific intestinal dysbiosis persists after multicompartmental injury

Jennifer A Munley  1 , Lauren S Kelly  2 , Gwoncheol Park  3 , Gwendolyn S Gillies  4 , Erick E Pons  5 , Kolenkode B Kannan  5 , Letitia E Bible  6 , Philip A Efron  5 , Ravinder Nagpal  3 , Alicia M Mohr  7
Affiliations

Sex-specific intestinal dysbiosis persists after multicompartmental injury

Jennifer A Munley et al. Surgery. 2023 Dec.

Abstract

Background: Preclinical studies of the gut microbiome after severe traumatic injury have demonstrated severe dysbiosis in males, with sex-specific microbial differences up to 2 days after injury. However, the impact of host sex on injury-driven dysbiosis over time remains unknown. We hypothesized that sex-specific differences in intestinal microbiome diversity and composition after traumatic injury with and without stress would persist after 7 days.

Methods: Male and proestrus female Sprague-Dawley rats (n = 8/group) were subjected to either polytrauma (lung contusion, hemorrhagic shock, cecectomy, bifemoral pseudofractures), polytrauma plus chronic restraint stress, or naïve controls. The fecal microbiome was measured on days 0, 3, and 7 using 16S rRNA sequencing and Quantitative Insights into Microbial Ecology bioinformatics analyses. Microbial alpha-diversity (Chao1 and Shannon indices) and beta-diversity were assessed. Analyses were performed in GraphPad and "R," with significance defined as P < .05.

Results: Polytrauma and polytrauma plus chronic restraint stress reduced alpha-diversity (Chao1, Shannon) within 3 days postinjury, which persisted up to day 7 in both sexes; polytrauma and polytrauma plus chronic restraint stress females had significantly decreased Chao1 compared to male counterparts at day 7 (P = .02). At day 7, the microbiome composition in polytrauma females had higher proportion of Mucispirillum, whereas polytrauma plus chronic restraint stress males demonstrated elevated abundance of Ruminococcus and Akkermansia.

Conclusion: Multicompartmental trauma induces intestinal dysbiosis that is sex-specific with persistence of decreased diversity and unique "pathobiome" signatures in females after 1 week. These findings underline sex as an important biological variable that may influence variable host-specific responses and outcomes after severe trauma and critical illness. This underscores the need to consider precision medicine strategies to ameliorate these outcomes.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest/Disclosure

The authors have no conflicts of interests or disclosures to report.

Figures

Figure 1.
Figure 1.
Alpha-diversity at each time point represented by (A) Chao1 index at day 3, (B) Chao1 index at day 7, (C) Shannon index at day 3, and (D) Shannon index at day 7. Only statistically significant comparisons displayed (*P < .05). PT/CS, polytrauma/chronic stress.
Figure 2.
Figure 2.
Principal coordinate analysis plots showing changes in beta-diversity, the measure of differences in biodiversity between groups at (A) day 3 and (B) day 7. The percentage on each orthogonal axis represents the proportion of overall variance in the data. Genus-level microbiome composition between groups at (C) day 3 and (D) day 7. Unique microbial species identified with *P < .05. PT/CS, polytrauma/chronic stress.
Figure 3.
Figure 3.
Changes in alpha-diversity between males and females represented by the (A) Chao1 index at day 3, (B) Shannon index at day 3, (C) Chao1 index at day 7, and (D) Shannon index at day 7. Only statistically significant comparisons displayed (*P < .05). PT/CS, polytrauma/chronic stress.
Figure 4.
Figure 4.
Principal coordinate analysis plots showing changes in beta-diversity, the measure of differences in biodiversity between males and females within groups (A) at day 3 and (B) day 7. The percentage on each orthogonal axis represents the proportion of overall variance in the data. Genus-level microbiome composition between males and females (C) at day 3 and (D) at day 7 within cohorts. Unique microbial species identified with *P < .05. PT/CS, polytrauma/chronic stress.
Figure 5.
Figure 5.
Alpha-diversity changes over time within groups represented by (A) Chao1 index in males with polytrauma (PT), (B) Chao1 index in males with PT/chronic stress, (C) Shannon index in males with PT, (D) Shannon index in males with PT/chronic stress. Only statistically significant comparisons displayed (*P < .05). PT/CS, polytrauma/chronic stress.
Figure 6.
Figure 6.
Alpha-diversity changes over time within groups represented by (A) Chao1 index in females with polytrauma (PT), (B) Chao1 index in females with PT/chronic stress, (C) Shannon index in females with PT, (D) Shannon index in females with PT/chronic stress. Only statistically significant comparisons displayed (*P < .05). PT/CS, polytrauma/chronic stress.
Figure 7.
Figure 7.
Genus-level microbiome composition changes over time in cohorts in (A) males and (B) females. Unique microbial species identified with *P < .05. PT/CS, polytrauma/chronic stress.
See this image and copyright information in PMC

References

    1. Miller WD, Keskey R, Alverdy JC. Sepsis and the microbiome: a vicious cycle. J Infect Dis. 2021;223(Suppl 2):S264–S269. - PMC - PubMed
    1. Adelman MW, Woodworth MH, Langelier C, et al. The gut microbiome’s role in the development, maintenance, and outcomes of sepsis. Crit Care. 2020;24:278. - PMC - PubMed
    1. Nicholson SE, Burmeister DM, Johnson TR, et al. A prospective study in severely injured patients reveals an altered gut microbiome is associated with transfusion volume. J Trauma Acute Care Surg. 2019;86:573–582. - PMC - PubMed
    1. Burmeister DM, Johnson TR, Lai Z, et al. The gut microbiome distinguishes mortality in trauma patients upon admission to the emergency department. J Trauma Acute Care Surg. 2020;88:579–587. - PMC - PubMed
    1. Yang J, Zhang J, Zhao C, et al. Blood loss leads to increase in relative abundance of opportunistic pathogens in the gut microbiome of rabbits. Curr Microbiol. 2020;77:415–424. - PubMed

Substances

LinkOut - more resources