Investigating the impact of human blood metabolites on the Sepsis development and progression: a study utilizing two-sample Mendelian randomization

作者：Zhongqi Zhang, Yu Yin, Tingzhen Chen, Jinjin You, Wenhui Zhang, Yifan Zhao, Yankang Ren, Han Wang, Xiang‐Ding Chen, Xiangrong Zuo · 发表于：Frontiers in Medicine · 年份：2023 · DOI：10.3389/fmed.2023.1310391 · 被引用次数：12 · 研究领域：Metabolomics and Mass Spectrometry Studies、Sepsis Diagnosis and Treatment、Gut microbiota and health

Background: Existing data suggests a potential link between human blood metabolites and sepsis, yet the precise cause-and-effect relationship remains elusive. By using a two-sample Mendelian randomization (MR) analysis, this study aims to establish a causal link between human blood metabolites and sepsis. Methods: A two-sample MR analysis was employed to investigate the relationship between blood metabolites and sepsis. To assess the causal connection between sepsis and human blood metabolites, five different MR methods were employed, A variety of sensitivity analyses were conducted, including Cochrane's Q test, MR-Egger intercept test, MR-PRESSO and leave-one-out (LOO) analysis. In order to ensure the robustness of the causal association between exposure and outcome, the Bonferroni adjustment was employed. Additionally, we conducted analyses of the metabolic pathways of the identified metabolites using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Small Molecule Pathway Database (SMPDB) database. Results: The MR analysis revealed a total of 27 metabolites (16 known and 11 unknown) causally linked to the development and progression of sepsis. After applying the Bonferroni correction, 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) remained significant in relation to 28-day all-cause mortality in sepsis. By pathway enrichment analysis, we identified four significant metabolic pathways. Notably, the Alpha Linolenic Acid and Linoleic Acid metabolism pathway eme...