1312: Sex-Specific Intestinal Dysbiosis Persists After Multicompartmental Traumatic Injury

Munley, Jennifer A.; Kelly, Lauren; Gillies, Gwendolyn S; Pons, Erick E; Coldwell, Preston S; Kannan, Kolenkode B.; Efron, Philip A.; Nagpal, Ravinder; Mohr, Alicia M.

doi:10.1097/01.ccm.0000910984.65526.45

Cited by 2 publications

(11 citation statements)

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“…[8][9][10][11][12] Further investigation into dysbiosis after trauma has revealed sex-specific differences between males and females. [13][14][15] Similar findings of host sex influence on intestinal microbiome dysbiosis have also been demonstrated in sepsis. 16,17 Specifically, females have improved recovery of their microbiome after sepsis when compared with male counterparts in terms of diversity and microbial composition.…”

supporting

confidence: 63%

“…These findings in groups subjected to injury with or without stress alone align with other studies, which showed that severe injury results in such changes to the diversity and composition of the intestinal microbiome acutely and days after injury in a rat model of multicompartmental trauma with or without stress. 13,14,35 We were surprised to find that the addition of postinjury pneumonia did not result in a more severe decline in α-diversity compared with uninfected counterparts. However, the addition of sepsis did alter β-diversity and gut microbiome composition when comparing severely injured cohorts with or without stress compared with infected counterparts.…”

Section: Discussionmentioning

confidence: 91%

“…Other studies of longer durations of postinjury stress have demonstrated more effect on the intestinal microbiome. 14,35,37 Longer durations of stress have indeed demonstrated not only persistently low α-diversity but also unique microbial composition compared with unstressed counterparts. It is possible that, given the short duration of stress in this model, the full effects of prolonged stress were not observed in this study.…”

Section: Discussionmentioning

confidence: 99%

“…40,41 Our model includes cecectomy, which could also influence the microbiome given the exposure of the intestinal contents, but other studies have demonstrated intestinal microbiome changes postinjury without gastrointestinal tract manipulation. 2 We also only used one age group of animals for this study; future studies should investigate how age impacts the microbiome in a secondhit model. 21 In conclusion, the addition of pneumonia after severe injury resulted in a severe decline in α-diversity, shifts in βdiversity, and a loss of commensal bacteria with emergence of pathogenic bacteria in the gut microbiome acutely.…”

Section: Discussionmentioning

confidence: 99%

“…1 It has been implicated in many diseases and has specifically been shown to become a "pathobiome," characterized by decreased diversity and the emergence of opportunistic pathogenic organisms after trauma or sepsis. [2][3][4][5] The emergence of dysbiosis after injury has been further studied in trauma patients and correlations established between the severity of dysbiosis and hospital length of stay and mortality. 6 In postsurgical patients, severity of dysbiosis has been correlated to sepsis progression.…”

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confidence: 99%

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Acute emergence of the intestinal pathobiome after postinjury pneumonia

Munley,

Kelly,

Park

et al. 2024

J Trauma Acute Care Surg

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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 polytrauma (PT) (lung contusion, hemorrhagic shock, cecectomy, bifemoral pseudofracture), PT plus 2-hours 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 QIIME2 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 to naïve controls (p < 0.05). PT + PNA and PT/RS + PNA resulted in different β-diversity arrays compared to 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 to 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. PT/RS males had an abundance of Gastranaerophilales and Muribaculaceae. Conclusions Multicompartmental trauma complicated by sepsis significantly diminishes diversity and alters microbial composition towards 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. LEVEL OF EVIDENCE Not applicable – basic science

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supporting

confidence: 63%

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Acute emergence of the intestinal pathobiome after postinjury pneumonia

Munley,

Kelly,

Park

et al. 2024

J Trauma Acute Care Surg

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Dysregulated brain-gut axis in the setting of traumatic brain injury: review of mechanisms and anti-inflammatory pharmacotherapies

El Baassiri,

Raouf,

Badin

et al. 2024

J Neuroinflammation

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Traumatic brain injury (TBI) is a chronic and debilitating disease, associated with a high risk of psychiatric and neurodegenerative diseases. Despite significant advancements in improving outcomes, the lack of effective treatments underscore the urgent need for innovative therapeutic strategies. The brain-gut axis has emerged as a crucial bidirectional pathway connecting the brain and the gastrointestinal (GI) system through an intricate network of neuronal, hormonal, and immunological pathways. Four main pathways are primarily implicated in this crosstalk, including the systemic immune system, autonomic and enteric nervous systems, neuroendocrine system, and microbiome. TBI induces profound changes in the gut, initiating an unrestrained vicious cycle that exacerbates brain injury through the brain-gut axis. Alterations in the gut include mucosal damage associated with the malabsorption of nutrients/electrolytes, disintegration of the intestinal barrier, increased infiltration of systemic immune cells, dysmotility, dysbiosis, enteroendocrine cell (EEC) dysfunction and disruption in the enteric nervous system (ENS) and autonomic nervous system (ANS). Collectively, these changes further contribute to brain neuroinflammation and neurodegeneration via the gut-brain axis. In this review article, we elucidate the roles of various anti-inflammatory pharmacotherapies capable of attenuating the dysregulated inflammatory response along the brain-gut axis in TBI. These agents include hormones such as serotonin, ghrelin, and progesterone, ANS regulators such as beta-blockers, lipid-lowering drugs like statins, and intestinal flora modulators such as probiotics and antibiotics. They attenuate neuroinflammation by targeting distinct inflammatory pathways in both the brain and the gut post-TBI. These therapeutic agents exhibit promising potential in mitigating inflammation along the brain-gut axis and enhancing neurocognitive outcomes for TBI patients.

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1312: Sex-Specific Intestinal Dysbiosis Persists After Multicompartmental Traumatic Injury

Cited by 2 publications

References 0 publications

Acute emergence of the intestinal pathobiome after postinjury pneumonia

Acute emergence of the intestinal pathobiome after postinjury pneumonia

Dysregulated brain-gut axis in the setting of traumatic brain injury: review of mechanisms and anti-inflammatory pharmacotherapies

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