Hu Xiaoli, Zhang Yue, Wu Yuchao, Peng Miao
Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, People's Republic of China.
Department of Pain Management, The Affiliated Hospital of Southwest Medical University, Luzhou, People's Republic of China.
J Inflamm Res. 2025 May 28;18:6907-6926. doi: 10.2147/JIR.S503370. eCollection 2025.
Pressure ulcers (PU) are skin and soft tissue injuries caused by prolonged localized pressure, friction, or shear forces, particularly affecting individuals with limited mobility. Understanding the mechanisms behind PU formation, including the role of metabolites, is crucial for effective prevention.
We conducted a two-sample MR analysis to explore the causal relationship between circulating metabolites and PU. Exposure data included GWAS data for 1400 metabolites, while outcome data were sourced from a Finnish database. We used multiple MR methods (IVW, MR-Egger, WM, Simple mode, Weighted mode) to estimate causal effects and performed sensitivity analyses to assess robustness. Additionally, we validated the effects of key metabolites on PU through animal experiments.
A total of 19 metabolites demonstrated significant causal associations with PU (P < 0.01). Among them, 7 metabolites were linked to PU increased risk, the highest ORs was (IVW: OR [95% CI] = 1.3690 [1.0852-1.7270]; P = 0.0080) for the spermidine to choline ratio. 12 metabolites with positive effects on PU prevention, the homostachydrine levels showing a highest association (IVW: OR [95% CI] = 0.7497 [0.6206-0.9056]; P = 0.0028). Sensitivity analyses supported these findings and validated the stability of the results. In animal experiments, rats treated with HD-Hom and LR (Spe/Cho) showed the fastest scab shedding and new epithelial tissue formation, with the smallest residual wound area.
This study highlights significant causal relationships between circulating metabolites and PU risk. The identification of the spermidine to choline ratio as a risk factor and homostachydrine levels as a protective factor suggests potential metabolic targets for PU prevention and treatment.
压疮（PU）是由长期局部压力、摩擦或剪切力引起的皮肤和软组织损伤，尤其影响行动不便的个体。了解压疮形成背后的机制，包括代谢物的作用，对于有效预防至关重要。
我们进行了一项两样本孟德尔随机化（MR）分析，以探讨循环代谢物与压疮之间的因果关系。暴露数据包括1400种代谢物的全基因组关联研究（GWAS）数据，而结果数据来自芬兰的一个数据库。我们使用多种MR方法（逆方差加权法、MR-Egger回归法、加权中位数法、简单模式、加权模式）来估计因果效应，并进行敏感性分析以评估结果的稳健性。此外，我们通过动物实验验证了关键代谢物对压疮的影响。
共有19种代谢物与压疮表现出显著的因果关联（P < 0.01）。其中，7种代谢物与压疮风险增加有关，亚精胺与胆碱的比值的优势比最高（逆方差加权法：优势比[95%置信区间]=1.3690[1.0852 - 1.7270]；P = 0.0080）。12种代谢物对压疮预防有积极作用，高水苏碱水平的关联最为显著（逆方差加权法：优势比[95%置信区间]=0.7497[0.6206 - 0.9056]；P = 0.0028）。敏感性分析支持了这些发现，并验证了结果的稳定性。在动物实验中，用高剂量高水苏碱和低剂量（亚精胺/胆碱）处理的大鼠结痂脱落最快，新上皮组织形成最快，残余伤口面积最小。
本研究突出了循环代谢物与压疮风险之间的显著因果关系。将亚精胺与胆碱的比值确定为风险因素，高水苏碱水平确定为保护因素，为压疮的预防和治疗提供了潜在的代谢靶点。
