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Zheng, Amy Sulan (2025) The role of serum inflammatory modulators and the gut microbiome in musculoskeletal trauma. PhD thesis, University of Nottingham.

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Abstract

Introduction

Trauma is one of the leading causes of death in the world, the underlying inflammatory response and biological response to trauma is through to be related to the inflammatory cascade and is regularly monitored clinically in the form of physiological signs and symptoms. Surgery for traumatic injuries is common and there is emerging evidence that the gut microbiome has a part to play in the outcomes associated with traumatic injury. This thesis aims to understand the physiology behind trauma in the context of high-energy rib fracture patients and utilises the inflammatory cytokines, bioactive lipids and endocannabinoids within serum as biomarkers to predict disease and pain.

Methods

Patients were recruited from three cohorts, low-energy frail trauma, high-energy chest trauma and healthy control as comparison groups. Serum and faecal samples were taken for analysis of cytokine, bioactive lipids, endocannabinoid and gut microbiome. Comparison was performed between cohorts with baseline expressions adjusted for age, sex and BMI. For the high-energy cohort comparison was also made with paired testing pre and post-surgery and over time. Gut microbiome diversity analysis was performed utilising alpha and beta diversity metrics.

Results

Patients that have undergone trauma have a higher expression of inflammatory cytokines including IL-6, IL-17a and IL-10, decreased expression of osteoclastic associated modulators including RANKL, CCL3 and CXCL. Immune modulators that change with surgery and time include wound healing mediators CCL4 and IL-22RA, bone metabolism mediators OPG and OSM and inflammatory regulators from the IL-10 superfamily and IFN-γ. Bioactive lipids including16-HETE, 5-HETE, 9-HODE, and 9-oxoODE had lower expression in trauma patients, indicating alterations in inflammation regulation and oxidative stress pathways. Bioactive lipids including 16-HETE, DHA and EPA are predictive of analgesic requirements. Over time, resolvins that are associated with healing are up regulated in surgical patients. Gut diversity indices including richness were less diverse in trauma patients compared with control, with reduced species diversity and less unique species in trauma microbiomes.

Conclusions

Inflammatory mediators are present in abundance in traumatised patients. There is a unique profile for trauma population and changes are seen with surgery and over time. These modulators are associated with clinical parameters relating to pain and are predictive of trauma. The study reveals some of the roles of the inflammasome and it’s associations with the gut microbiome within musculoskeletal trauma.

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	Ollivere, Ben Valdes, Ana
Keywords:	Trauma, Physiological effects, Inflammatory response, Gut microbiome, Inflammatory cytokines, Bioactive lipids, Endocannabinoids
Subjects:	W Medicine and related subjects (NLM Classification) > WO Surgery
Faculties/Schools:	UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID:	80577
Depositing User:	zheng, Amy
Date Deposited:	23 Jul 2025 04:40
Last Modified:	23 Jul 2025 04:40
URI:	https://eprints.nottingham.ac.uk/id/eprint/80577

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