Background: The incidence of idiopathic pulmonary fibrosis (IPF) is increasing every year; however, the potential biological mechanisms have not been completely clarified. The objective of this study is to reveal the etiologic effects of circulating metabolites on IPF.

Methods: This research evaluated the causal relationship between serum metabolites and IPF utilizing two-sample Mendelian randomization (MR) analysis. IVW served as the main method of analysis; concurrently, MR-Egger, weighted median, and MR-PRESSO acted as supplementary analyses. Sensitivity analyses were performed with Cochran's Q test, MR-Egger's intercept test, and leave-one-out method of analysis. All statistical analyses were accomplished in R software.

Results: Our results showed that 23 metabolites have a causal connection with IPF. Following sensitivity analysis, 2 robust and 12 potential causal association pairs were identified among the known metabolites. These 14 causal pairs concerned six metabolites.

Conclusion: This study presents a novel perspective on potential mechanisms involved in IPF with important significance for screening, prevention, and treatment.

Keywords: Mendelian randomization; causality; idiopathic pulmonary fibrosis; serum metabolites.

© 2025 The Author(s). The Clinical Respiratory Journal published by John Wiley & Sons Ltd.

背景： 特发性肺纤维化（IPF）的发病率每年都在增加，然而潜在的生物学机制尚未完全阐明。本研究旨在揭示循环代谢物对IPF病因效应的影响。

方法： 本研究利用两样本孟德尔随机化（MR）分析评估了血清代谢物与IPF之间的因果关系。IVW作为主要的分析方法，同时使用MR-Egger、加权中位数和MR-PRESSO作为补充分析方法。采用Cochran's Q检验、MR-Egger截距测试以及剔除法进行敏感性分析。所有统计分析均在R软件中完成。

结果： 我们的结果显示，23种代谢物与IPF之间存在因果联系。经过敏感性分析后，在已知的代谢物中识别出2对稳健和12对潜在因果关联。这14个因果关联涉及6种代谢物。

结论： 本研究为探索IPF可能的机制提供了一个新颖视角，并具有重要的筛查、预防和治疗意义。

关键词： 孟德尔随机化；因果关系；特发性肺纤维化；血清代谢物。