Zhao Jiajing, Wang Yuhan, Lv Chuxin, Peng Jiang, Lu Shu, Shen Lijuan
Internal Medicine of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing City, Jiangsu Province, China.
Department of Cardiology, Wuxi Traditional Chinese Medicine Hospital, Wuxi City, Jiangsu Province, China.
Cell Biochem Biophys. 2025 May 28. doi: 10.1007/s12013-025-01780-9.
This study investigates the causal relationships between gut microbiota (GM), plasma inflammatory proteins (PIPs), and valvular heart disease (VHD) using two-sample Mendelian Randomization (MR) analysis. We also assess whether PIPs mediate the link between GM and VHD. We conducted bidirectional MR analyses to explore causal associations between GM, PIPs, and VHD, and used multivariable MR to test the independence of associations. Genome-wide association study (GWAS) data on 196 GM taxa, 91 PIPs, and VHD were analyzed. MR methods including inverse-variance weighted (IVW), MR-Egger regression, and weighted median approaches were applied. Sensitivity analyses ensured robustness. Actinobacteria and Defluviitaleaceae were associated with lower VHD risk, while Oxalobacteraceae increased risk. At the genus level, Intestinibacter, Lachnospiraceae NC2004 group, Oscillospira, and Ruminococcaceae UCG004 were protective, whereas Oscillibacter increased risk. Among PIPs, Interleukin-10, Interleukin-17C, Leukemia inhibitory factor receptor (LIFR), and monocyte chemoattractant protein 2 were protective, while TNF-beta elevated risk. Multivariable MR confirmed the independent roles of TNF-beta, LIFR, and MCP-2. Actinobacteria's protective effect appeared partially mediated through increased LIFR expression, accounting for 14% of the effect. Our findings suggest that modulating gut microbiota, particularly enhancing Actinobacteria, may serve as a novel strategy for VHD prevention and treatment.
本研究采用两样本孟德尔随机化（MR）分析方法，探讨肠道微生物群（GM）、血浆炎症蛋白（PIPs）与心脏瓣膜病（VHD）之间的因果关系。我们还评估了PIPs是否介导GM与VHD之间的联系。我们进行了双向MR分析，以探索GM、PIPs和VHD之间的因果关联，并使用多变量MR来检验关联的独立性。分析了关于196种GM分类群、91种PIPs和VHD的全基因组关联研究（GWAS）数据。应用了包括逆方差加权（IVW）、MR-Egger回归和加权中位数方法在内的MR方法。敏感性分析确保了结果的稳健性。放线菌门和脱铁杆菌科与较低的VHD风险相关，而草酸杆菌科则增加风险。在属水平上，肠杆菌属、毛螺菌科NC2004组、颤螺菌属和瘤胃球菌科UCG004具有保护作用，而颤杆菌属则增加风险。在PIPs中，白细胞介素-10、白细胞介素-17C、白血病抑制因子受体（LIFR）和单核细胞趋化蛋白2具有保护作用，而肿瘤坏死因子-β则增加风险。多变量MR证实了肿瘤坏死因子-β、LIFR和MCP-2的独立作用。放线菌门的保护作用似乎部分是通过增加LIFR表达介导的，占该作用的14%。我们的研究结果表明，调节肠道微生物群，特别是增强放线菌门，可能是预防和治疗VHD的一种新策略。
