Causal effects between gut microbiota and pulmonary arterial hypertension: A bidirectional Mendelian randomization study

Chenwei Zhang; Yujia Xi; Yukai Zhang; Peiyun He; Xuesen Su; Yishan Li; Mengyuan Zhang; Haizhao Liu; Xiao Yu; Yiwei Shi

doi:10.1016/j.hrtlng.2024.01.002

Causal effects between gut microbiota and pulmonary arterial hypertension: A bidirectional Mendelian randomization study

Heart Lung. 2024 Mar-Apr:64:189-197. doi: 10.1016/j.hrtlng.2024.01.002. Epub 2024 Jan 29.

Authors

Chenwei Zhang¹, Yujia Xi², Yukai Zhang³, Peiyun He⁴, Xuesen Su⁴, Yishan Li³, Mengyuan Zhang⁴, Haizhao Liu⁵, Xiao Yu⁶, Yiwei Shi⁷

Affiliations

¹ NHC Key Laboratory of Pneumoconiosis, Shanxi Key Laboratory of Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan 030000, China; First Clinical Medical College, Shanxi Medical University, Taiyuan, China.
² Department of Urology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
³ NHC Key Laboratory of Pneumoconiosis, Shanxi Key Laboratory of Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan 030000, China.
⁴ First Clinical Medical College, Shanxi Medical University, Taiyuan, China.
⁵ People's Hospital, Shuozhou, Shanxi, China.
⁶ NHC Key Laboratory of Pneumoconiosis, Shanxi Key Laboratory of Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan 030000, China. Electronic address: yuxiaowz@163.com.
⁷ NHC Key Laboratory of Pneumoconiosis, Shanxi Key Laboratory of Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan 030000, China. Electronic address: shiyw@sxmu.edu.cn.

PMID: 38290183
DOI: 10.1016/j.hrtlng.2024.01.002

Abstract

Background: 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.

Objectives: 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.

Methods: 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.

Results: The results indicate that Genus Ruminococcaceae UCG004 (OR = 0.407, P = 0.031) and Family Alcaligenaceae (OR = 0.244, P = 0.014) were protective factors for PAH. Meanwhile Genus Lactobacillus (OR = 2.446, P = 0.013), Class Melainabacteria (OR = 2.061, P = 0.034), Phylum Actinobacteria (OR = 3.406, P = 0.010), Genus Victivallis (OR = 1.980, P = 0.010), Genus Dorea (OR = 3.834, P = 0.024) and Genus Slackia (OR = 2.622, P = 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.

Conclusions: This study explores the causal effects of eight gut microbial taxa on PAH and provides new ideas for early prevention of PAH.

Keywords: Causal effect; Gut microbiota; Lung-gut axis; Mendelian randomization; Pulmonary arterial hypertension.

MeSH terms

Familial Primary Pulmonary Hypertension
Gastrointestinal Microbiome* / genetics
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis
Pulmonary Arterial Hypertension* / epidemiology
Pulmonary Arterial Hypertension* / genetics