Blood metabolites mediate causal inference studies on the effect of gut microbiota on the risk of vascular calcification

作者：Aoran Huang, Jianshuai Ma, Huijin Zhu, Yanli Qi, Yang Jin, Mingxuan Zhang, Li Yin, Minhong Luo, Sifan Chen, Chen Xie, Hui Huang · 发表于：Journal of Advanced Research · 年份：2025 · DOI：10.1016/j.jare.2025.03.038 · 被引用次数：8 · 研究领域：Gut microbiota and health、Parathyroid Disorders and Treatments、Metabolomics and Mass Spectrometry Studies

• 19 gut microbiota were found to regulate the progression of VC, and the occurrence of VC led to changes in the abundance of 24 gut microbiota. • 52 metabolites were identified as regulators of VC progression, and the occurrence of VC led to changes in the abundance of 56 metabolites. • For the first time, we report that the gut microbiota g_KLE1615 promotes VC by regulating methionine and phosphate metabolism in the host. • Further basic experiment confirms the inhibitory effect of methionine on VC. • Our study provides new insights into the pathogenesis of VC and deepens our understanding of the gut-vascular axis. Emerging evidence indicates a notable connection between gut microbiota and Vascular Calcification (VC). Gut microbiota influences various disease processes through host metabolic pathways; however, the causative link between gut microbiota and VC, along with the potential mediating role of metabolites, is still not well understood. We leveraged data from the largest Genome-Wide Association Studies (GWAS) concerning gut microbiota, blood metabolites, and VC. To explore the causal relationships among these variables, we conducted two-sample bidirectional Mendelian Randomization (MR) analyses. Furthermore, mediation analyses were conducted to determine if metabolites act as an intermediary in the impact of gut microbiota on VC. In addition, we recruited CKD patients for mass spectrometry and CT examination, and performed a correlation analysis between the expressio...