Multiple studies have highlighted a potential link between gut microbes and the onset of Pulmonary Arterial Hypertension (PAH). Nonetheless, the precise cause-and-effect relationship remains uncertain. In this investigation, we utilized a two-sample Mendelian randomization (TSMR) approach to probe the presence of a causal connection between gut microbiota and PAH. Genome-wide association (GWAS) data for gut microbiota and PAH were sourced from MiBioGen and FinnGen research, respectively. Inverse variance weighting (IVW) was used as the primary method to explore the causal effect between gut flora and PAH, supplemented by MR-Egger, weighted median (WM). Sensitivity analyses examined the robustness of the MR results. Reverse MR analysis was used to rule out the effect of reverse causality on the results. The results indicate that Genus Ruminococcaceae UCG004 (OR = 0.407, = 0.031) and Family Alcaligenaceae (OR = 0.244, = 0.014) were protective factors for PAH. Meanwhile Genus Lactobacillus (OR = 2.446, = 0.013), Class Melainabacteria (OR = 2.061, = 0.034), Phylum Actinobacteria (OR = 3.406, = 0.010), Genus Victivallis (OR = 1.980, = 0.010), Genus Dorea (OR = 3.834, = 0.024) and Genus Slackia (OR = 2.622, = 0.039) were associated with an increased Prevalence of PAH. Heterogeneity and pleiotropy were not detected by sensitivity analyses, while there was no reverse causality for these nine specific gut microorganisms. This study explores the causal effects of eight gut microbial taxa on PAH and provides new ideas for early prevention of PAH.

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肠道微生物群与肺动脉高压之间的因果关系：双向孟德尔随机化研究

多项研究强调了肠道微生物与肺动脉高压（PAH）发病之间的潜在联系。尽管如此，确切的因果关系仍然不确定。在这项研究中，我们利用两个样本孟德尔随机化 (TSMR) 方法来探讨肠道微生物群与 PAH 之间是否存在因果关系。肠道微生物群和 PAH 的全基因组关联 (GWAS) 数据分别来自 MiBioGen 和 FinnGen 研究。以逆方差加权（IVW）作为探索肠道菌群与PAH之间因果关系的主要方法，并辅以MR-Egger、加权中位数（WM）。敏感性分析检验了 MR 结果的稳健性。采用反向MR分析来排除反向因果关系对结果的影响。结果表明瘤胃球菌属 UCG004 (OR = 0.407, = 0.031) 和产碱菌科 (OR = 0.244, = 0.014) 是 PAH 的保护因素。同时，乳杆菌属（OR = 2.446，= 0.013），黑色杆菌纲（OR = 2.061，= 0.034），放线菌门（OR = 3.406，= 0.010），Vitivallis属（OR = 1.980，= 0.010），Dorea属（OR = 3.834，= 0.024）和 Slackia 属（OR = 2.622，= 0.039）与 PAH 患病率增加相关。敏感性分析未检测到异质性和多效性，而这九种特定肠道微生物不存在反向因果关系。该研究探讨了八种肠道微生物类群对PAH的因果影响，为PAH的早期预防提供新思路。