Zou Qiong-Chao, Hu Jun-Pei, Cao Yan, She Chang, Liang Li-Hui, Liu Zheng-Yu
Cardiology Department, Hunan Provincial People's Hospital, Changsha, 410000, Hunan Province, China.
The First Affiliated Hospital of Hunan Normal University, Hunan Provincial People's Hospital, Changsha, 410000, Hunan Province, China.
Heliyon. 2024 Aug 10;10(16):e36125. doi: 10.1016/j.heliyon.2024.e36125. eCollection 2024 Aug 30.
Idiopathic pulmonary fibrosis (IPF) is an irreversible lung disease with unclear pathological mechanisms. In this study, we utilized bidirectional Mendelian randomization (MR) to analyze the relationship between serum metabolites and IPF, and conducted metabolic pathway analysis
To determine the causal relationship between serum metabolites and IPF using MR analysis.
A two-sample MR analysis was conducted to evaluate the causal relationship between 824 serum metabolites and IPF. The inverse variance weighted (IVW) method was used to estimate the causal relationship between exposure and results. Sensitivity analysis was conducted using MR Egger, weighted median, and maximum likelihood to eliminate pleiotropy. Additionally, metabolic pathway analysis was conducted to identify potential metabolic pathways.
We identified 12 serum metabolites (6 risks and 6 protective) associated with IPF from 824 metabolites. Among them, 11 were known and 1 was unknown. 1-Eicosatrienoylglycophorophospholine and 1-myristoylglycophorophospholine were bidirectional MR positive factors, with 1-myristoylglycophorophospholine being a risk factor (1.0013, 1.0097) and 1-eicosatrienoylglycophorine being a protective factor (0.9914, 0.9990). The four lipids (1-linoleoylglycerophoethanolamine*, total cholesterol in large high-density lipoprotein [HDL], cholesterol esters in very large HDL, and phospholipids in very large HDL) and one NA metabolite (degree of unsaturation) were included in the known hazardous metabolites. The known protective metabolites included three types of lipids (carnitine, 1-linoleoylglycerophoethanolamine*, and 1-eicosatrienoylglycerophophophorine), one amino acid (hypoxanthine), and two unknown metabolites (the ratio of omega-6 fatty acids to omega-3 fatty acids, and the ratio of photoshopids to total lipids ratio in chylomicrons and extremely large very low-density lipoprotein [VLDL]). Moreover, sn-Glycerol 3-phosphate and 1-Acyl-sn-glycero-3-phosphocline were found to be involved in the pathogenesis of IPF through metabolic pathways such as Glycerolide metabolism and Glycerophospholipid metabolism.
Our study identified 6 causal risks and 6 protective serum metabolites associated with IPF. Additionally, 2 metabolites were found to be involved in the pathogenesis of IPF through metabolic pathways, providing a new perspective for further understanding the metabolic pathway and the pathogenesis of IPF.
特发性肺纤维化（IPF）是一种病理机制不明的不可逆性肺部疾病。在本研究中，我们利用双向孟德尔随机化（MR）分析血清代谢物与IPF之间的关系，并进行了代谢途径分析。
采用MR分析确定血清代谢物与IPF之间的因果关系。
进行两样本MR分析，以评估824种血清代谢物与IPF之间的因果关系。采用逆方差加权（IVW）方法估计暴露与结果之间的因果关系。使用MR Egger、加权中位数和最大似然法进行敏感性分析，以消除多效性。此外，进行代谢途径分析以识别潜在的代谢途径。
我们从824种代谢物中鉴定出12种与IPF相关的血清代谢物（6种风险代谢物和6种保护代谢物）。其中，11种是已知的，1种是未知的。1-二十碳三烯酰糖基磷酰胆碱和1-肉豆蔻酰糖基磷酰胆碱是双向MR阳性因子，1-肉豆蔻酰糖基磷酰胆碱是风险因子（1.0013，1.0097），1-二十碳三烯酰糖基磷酰胆碱是保护因子（0.9914，0.9990）。四种脂质（1-亚油酰甘油磷酰乙醇胺*、大高密度脂蛋白（HDL）中的总胆固醇、超大HDL中的胆固醇酯和超大HDL中的磷脂）和一种NA代谢物（不饱和度）被纳入已知的有害代谢物中。已知的保护代谢物包括三种脂质（肉碱、1-亚油酰甘油磷酰乙醇胺*和1-二十碳三烯酰甘油磷酰胆碱）、一种氨基酸（次黄嘌呤）和两种未知代谢物（ω-6脂肪酸与ω-3脂肪酸的比例以及乳糜微粒和超大极低密度脂蛋白（VLDL）中磷脂与总脂质的比例）。此外，发现sn-甘油3-磷酸和1-酰基-sn-甘油-3-磷酰胆碱通过甘油酯代谢和甘油磷脂代谢等代谢途径参与IPF的发病机制。
我们的研究确定了6种与IPF相关的因果风险血清代谢物和6种保护血清代谢物。此外，发现2种代谢物通过代谢途径参与IPF的发病机制，为进一步了解IPF的代谢途径和发病机制提供了新的视角。
