Causal impact of gut microbiota and associated metabolites on pulmonary arterial hypertension: a bidirectional Mendelian randomization study

作者：Xin Li, Jiang‐Shan Tan, Jing Xu, Zhihui Zhao, Qing Zhao, Yi Zhang, Anqi Duan, Zhihua Huang, Sicheng Zhang, Luyang Gao, Yue Jin Yang, Tao Yang, Tao Yang, Qi Jin, Qin Luo, Yanmin Yang, Yanmin Yang, Zhihong Liu · 发表于：BMC Pulmonary Medicine · 年份：2024 · DOI：10.1186/s12890-024-03008-7 · 被引用次数：9 · 研究领域：Gut microbiota and health、Pulmonary Hypertension Research and Treatments、Genetic Associations and Epidemiology

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) exhibit a distinct gut microbiota profile; however, the causal association between gut microbiota, associated metabolites, and PAH remains elusive. We aimed to investigate this causal association and to explore whether dietary patterns play a role in its regulation. METHODS: Summary statistics of gut microbiota, associated metabolites, diet, and PAH were obtained from genome-wide association studies. The inverse variance weighted method was primarily used to measure the causal effect, with sensitivity analyses using the weighted median, weighted mode, simple mode, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger methods. A reverse Mendelian randomisation analysis was also performed. RESULTS: Alistipes (odds ratio [OR] = 2.269, 95% confidence interval [CI] 1.100-4.679, P = 0.027) and Victivallis (OR = 1.558, 95% CI 1.019-2.380, P = 0.040) were associated with an increased risk of PAH, while Coprobacter (OR = 0.585, 95% CI 0.358-0.956, P = 0.032), Erysipelotrichaceae (UCG003) (OR = 0.494, 95% CI 0.245-0.996, P = 0.049), Lachnospiraceae (UCG008) (OR = 0.596, 95% CI 0.367-0.968, P = 0.036), and Ruminococcaceae (UCG005) (OR = 0.472, 95% CI 0.231-0.962, P = 0.039) protected against PAH. No associations were observed between PAH and gut microbiota-derived metabolites (trimethylamine N-oxide [TMAO] and its precursors betaine, carnitine, and choline), short-chain fatty acids (SCFAs), or diet. Although inve...