Harvard Medical School, Harvard University, Boston, MA, United States.
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, United States.
Front Public Health. 2023 Jun 2;11:1105163. doi: 10.3389/fpubh.2023.1105163. eCollection 2023.
Burn injury in children causes prolonged systemic effects on physiology and metabolism leading to increased morbidity and mortality, yet much remains undefined regarding the metabolic trajectory towards specific health outcomes.
A multi-platform strategy was implemented to evaluate the long-term immuno-metabolic consequences of burn injury combining metabolite, lipoprotein, and cytokine panels. Plasma samples from 36 children aged 4-8 years were collected 3 years after a burn injury together with 21 samples from non-injured age and sex matched controls. Three different H Nuclear Magnetic Resonance spectroscopic experiments were applied to capture information on plasma low molecular weight metabolites, lipoproteins, and α-1-acid glycoprotein.
Burn injury was characterized by underlying signatures of hyperglycaemia, hypermetabolism and inflammation, suggesting disruption of multiple pathways relating to glycolysis, tricarboxylic acid cycle, amino acid metabolism and the urea cycle. In addition, very low-density lipoprotein sub-components were significantly reduced in participants with burn injury whereas small-dense low density lipoprotein particles were significantly elevated in the burn injured patient plasma compared to uninjured controls, potentially indicative of modified cardiometabolic risk after a burn. Weighted-node Metabolite Correlation Network Analysis was restricted to the significantly differential features (q <0.05) between the children with and without burn injury and demonstrated a striking disparity in the number of statistical correlations between cytokines, lipoproteins, and small molecular metabolites in the injured groups, with increased correlations between these groups.
These findings suggest a 'metabolic memory' of burn defined by a signature of interlinked and perturbed immune and metabolic function. Burn injury is associated with a series of adverse metabolic changes that persist chronically and are independent of burn severity and this study demonstrates increased risk of cardiovascular disease in the long-term. These findings highlight a crucial need for improved longer term monitoring of cardiometabolic health in a vulnerable population of children that have undergone burn injury.
儿童烧伤会对其生理和代谢产生长期的全身性影响,导致发病率和死亡率增加,但对于烧伤后特定健康结局的代谢轨迹,仍有许多方面尚未明确。
本研究采用多平台策略,结合代谢物、脂蛋白和细胞因子谱,评估烧伤后儿童的长期免疫代谢后果。收集了 36 名 4-8 岁烧伤儿童在烧伤 3 年后的血浆样本,并与 21 名年龄和性别匹配的未受伤对照者的血浆样本进行了比较。应用三种不同的 H 核磁共振波谱实验来获取有关血浆低分子量代谢物、脂蛋白和α-1-酸性糖蛋白的信息。
烧伤的特征是存在高血糖、高代谢和炎症的潜在特征,这表明与糖酵解、三羧酸循环、氨基酸代谢和尿素循环相关的多种途径受到了破坏。此外,烧伤患儿的极低密度脂蛋白亚组份明显减少,而烧伤患儿的小而密低密度脂蛋白颗粒明显高于未受伤对照组,这可能表明烧伤后心血管代谢风险发生了改变。加权节点代谢物相关网络分析仅限于烧伤患儿和未烧伤患儿之间有显著差异的特征(q <0.05),结果表明,在烧伤组中,细胞因子、脂蛋白和小分子代谢物之间的统计相关性数量存在显著差异,这些组之间的相关性增加。
这些发现表明,烧伤的“代谢记忆”由相互关联和紊乱的免疫和代谢功能的特征定义。烧伤与一系列持续存在的慢性代谢变化相关,且与烧伤严重程度无关,本研究表明,烧伤儿童长期存在心血管疾病风险增加。这些发现强调了在经历烧伤的脆弱人群中,需要更好地监测长期的心血管代谢健康。