Deng Ruiming, Huang Guiming, Zhou Juan, Zeng Kai
Department of Anesthesiology, Ganzhou People's Hospital, Ganzhou City, Jiangxi Provence, China.
Department of Thyroid and Breast Surgery, Ganzhou People's Hospital, Ganzhou City, Jiangxi Provence, China.
Shock. 2025 Jan 1;63(1):52-63. doi: 10.1097/SHK.0000000000002465. Epub 2024 Aug 28.
Background : The interrelation between the plasma proteome and plasma metabolome with sepsis presents a multifaceted dynamic that necessitates further research to elucidate the underlying causal mechanisms. Methods : Our investigation used public genome-wide association study data to explore the relationships among the plasma proteome, metabolome, and sepsis, considering different sepsis subgroup. Initially, two-sample Mendelian randomization established causal connections between the plasma proteome and metabolome with sepsis. Subsequently, multivariate and iterative Mendelian randomization analyses were performed to understand the complex interactions in plasma during sepsis. The validity of these findings was supported by thorough sensitivity analyses. Result : The study identified 25 plasma proteins that enhance risk and 34 that act as protective agents in sepsis. After P value adjustment (0.05/1306), ICAM5 emerged with a positive correlation to sepsis susceptibility ( P value = 2.14E-05, OR = 1.10, 95% CI = 1.05-1.15), with this significance preserved across three sepsis subgroup examined. Additionally, 29 plasma metabolites were recognized as risk factors, and 15 as protective factors for sepsis outcomes. After P value adjustment (0.05/997), elevated levels of 1,2,3-benzenetriol sulfate (2) was significantly associated with increased sepsis risk ( P value = 3.37E-05, OR = 1.18, 95% CI = 1.09-1.28). Further scrutiny revealed that this plasma metabolite notably augments the abundance of ICAM5 protein ( P value = 3.52E-04, OR = 1.11, 95% CI = 1.04-1.17), devoid of any detected heterogeneity, pleiotropy, or reverse causality. Mediated Mendelian randomization revealed ICAM5 mediated 11.9% of 1,2,3-benzenetriol sulfate (2)'s total effect on sepsis progression. Conclusion : This study details the causal link between the plasma proteome and metabolome with sepsis, highlighting the roles of ICAM5 and 1,2,3-benzenetriol sulfate (2) in sepsis progression, both independently and through crosstalk.
脓毒症患者血浆蛋白质组和代谢组之间的相互关系呈现出多方面的动态变化，需要进一步研究以阐明潜在的因果机制。方法：我们的研究利用公开的全基因组关联研究数据，探讨血浆蛋白质组、代谢组与脓毒症之间的关系，同时考虑不同的脓毒症亚组。首先，两样本孟德尔随机化分析建立了血浆蛋白质组、代谢组与脓毒症之间的因果联系。随后，进行多变量和迭代孟德尔随机化分析，以了解脓毒症期间血浆中的复杂相互作用。全面的敏感性分析支持了这些发现的有效性。结果：该研究确定了25种增加脓毒症风险的血浆蛋白和34种起保护作用的血浆蛋白。在P值调整（0.05/1306）后，细胞间黏附分子5（ICAM5）与脓毒症易感性呈正相关（P值 = 2.14×10⁻⁵，比值比[OR]=1.10，95%置信区间[CI]=1.05 - 1.15），在三个研究的脓毒症亚组中均保持这一显著性。此外，29种血浆代谢物被确定为脓毒症结局的危险因素，15种为保护因素。在P值调整（0.05/997）后，硫酸1,2,3 -苯三醇（2）水平升高与脓毒症风险增加显著相关（P值 = 3.37×10⁻⁵，OR = 1.18，95% CI = 1.09 - 1.28）。进一步研究发现，这种血浆代谢物显著增加了ICAM5蛋白的丰度（P值 = 3.52×10⁻⁴，OR = 1.11，95% CI = 1.04 - 1.17），未检测到任何异质性、多效性或反向因果关系。中介孟德尔随机化分析显示，ICAM5介导了硫酸1,2,3 -苯三醇（2）对脓毒症进展总效应的11.9%。结论：本研究详细阐述了血浆蛋白质组、代谢组与脓毒症之间的因果联系，突出了ICAM5和硫酸1,2,3 -苯三醇（2）在脓毒症进展中的独立作用以及通过相互作用发挥的作用。
