Causal association between gut microbiota and pulmonary embolism: a 2-sample Mendelian randomization study

Abstract

Background: Pulmonary embolism (PE) is the third most common cause of cardiovascular-related deaths globally; however, the causal relationship between gut microbiota and PE remains unclear. This study aimed to explore the impact of gut microbiota on PE.

Methods: This study utilized a 2-sample Mendelian randomization (MR) design to analyze gut microbiota genome-wide association study data from the MiBioGen database and PE data from the FinnGen database. Statistical methods, such as inverse variance-weighted, MR-Egger, weighted median, and weighted modes, were used to investigate the causal relationship between the gut microbiota and PE. Moreover, a sensitivity analysis was conducted to assess the robustness of the results.

Results: MR analysis revealed that gut microbiota genera Intestinimonas (odds ratio [OR]: 0.797; 95% confidence interval [CI]: 0.666-0.952; P = 0.013) and Roseburia (OR: 0.752; 95% CI: 0.575-0.984; P = 0.038) have a protective effect on PE. Conversely, an increased abundance of the phylum Lentisphaerae (OR: 1.217; 95% CI: 1.033-1.434; P = 0.019), class Lentisphaeria (OR: 1.219; 95% CI: 1.010-1.471; P = 0.039), order Gastranaerophilales (OR: 1.209; 95% CI: 1.017-1.437; P = 0.031), order Victivallales (OR: 1.219; 95% CI: 1.010-1.471; P = 0.039), and the genus Ruminococcus gauvreauii (OR: 1.274; 95% CI: 1.015-1.599; P = 0.037) increases the risk of developing PE. Sensitivity analysis indicated no heterogeneity or horizontal pleiotropy.

Conclusion: Seven gut microbiotas, including the phylum Lentisphaerae, class Lentisphaeria, orders Gastranaerophilales and Victivallales, and genera R. gauvreauii, Intestinimonas, and Roseburia, were causally associated with PE. These findings may contribute significantly to the prevention of PE through dietary modifications and microbiome interventions.

Keywords

Causal relationship / Gut microbiota / Mendelian randomization / Pulmonary embolism

Conflict of interest statement

The authors declare no conflict of interest.

Author contributions

He S conceived the study, completed the database search, screened and extracted data, and wrote the manuscript. Song R analyzed and interpreted the data. Li Z inspected and verified the data. Shi S revised the finished manuscript. Pang J provided suggestions on summarizations and statistical analysis. All authors have read and approved the final version of this manuscript.

Funding

This study was supported by National Natural Science Foundation of China (82302433), Natural Science Foundation of Shandong Province (ZR2023QH324, ZR2022QH018), Taishan Young Scholar Program of Shandong Province (tsqn202306353), China InternationalMedical Foundation (Z-2017-24-2421).

Ethical approval of studies and informed consent

This study used only publicly available data from studies involving human participants, with written informed consent and approval by their respective institutional ethics review committees.

Acknowledgment

The data analyzed in this study were provided by MiBioGen consortium, FinnGen, and UK Biobank. We gratefully acknowledge their contributing studies and the participants in the corresponding studies without whom this effort would not be possible.

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