The metabolomic response to severe thermal injury and the impact of age

Wearn, Christopher Michael Francis (2017). The metabolomic response to severe thermal injury and the impact of age. University of Birmingham. Ph.D.

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Abstract

Severe thermal injury results in a profound hypermetabolic response and is associated with increased morbidity, mortality and delayed rehabilitation of burn survivors. Serum 1H-NMR metabolomics was used to examine early global metabolic changes in the response to severe thermal injury (>15% TBSA) in young adults (16-64 years) and older adults (<15% TBSA). Early changes in the metabolome reflected hypoxic metabolism, hyperglycaemia, increased ketogenesis, peripheral lipolysis and increased energy production in both cohorts. Early metabolic profiles from the young adult group were used to construct OPLSDA models that could discriminate with high accuracy between outcome groups. Models from 0-24hrs serum samples predicted survival (AUC 0.92), whilst models from 24-96hrs samples predicted Multiple organ failure (MOF) (AUC 0.92) and sepsis (AUC 0.89). Untargeted LC-MS metabolomics was applied to study the longitudinal changes in the serum metabolome after severe thermal injury in 13 young adults, from admission until 6-months post-injury. Univariate ANOVA analysis revealed significant changes in 432 metabolite features, affecting 35 distinct classes, representing global metabolic disturbance. Changes in 300 lipid metabolite features may represent a ‘lipid storm’ in serum after severe thermal injury. Novel areas of metabolism and metabolites were identified as putative biomarkers warranting further targeted study.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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