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BMC Pulmonary Medicine

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Open Access 01-12-2024 | Respiratory Microbiota | Research

Genetically determined gut microbiota associates with pulmonary arterial hypertension: a Mendelian randomization study

Authors: Ye Yuan, Shan Li, Manrong Yan, Yan Yang, Changming Zhong, Yijie Hu

Published in: BMC Pulmonary Medicine | Issue 1/2024

Abstract

Background

Emerging evidences have demonstrated that gut microbiota composition is associated with pulmonary arterial hypertension (PAH). However, the underlying causality between intestinal dysbiosis and PAH remains unresolved.

Method

An analysis using the two-sample Mendelian randomization (MR) approach was conducted to examine the potential causal relationship between gut microbiota and PAH. To assess exposure data, genetic variants associated with 196 bacterial traits were extracted from the MiBioGen consortium, which included a sample size of 18,340 individuals. As for the outcomes, summary statistics for PAH were obtained from the NHGRI-EBI GWAS Catalog, which conducted a meta-analysis of four independent studies comprising a total of 11,744 samples. Causal effects were estimated employing various methods, including inverse variance weighted (IVW), MR-Egger, weighted median, weight mode and simple mode, with sensitivity analyses also being implemented with Cochran’s Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots.

Results

Following false discovery rate (FDR) correction, the genetically predicted genus Eubacterium fissicatena group (odds ratio (OR) 1.471, 95% confidence interval (CI) 1.178–1.837, q = 0.076) exhibited a causal association with PAH. In addition, the genus LachnospiraceaeUCG004 (OR 1.511, 95% CI 1.048–2.177) and genus RuminococcaceaeUCG002 (OR 1.407, 95% CI 1.040–1.905) showed a suggestive increased risk of PAH, while genus Eubacterium eligens group (OR 0.563, 95% CI 0.344–0.922), genus Phascolarctobacterium (OR 0.692, 95% CI 0.487–0.982), genus Erysipelatoclostridium (OR 0.757, 95% CI 0.579–0.989) and genus T–yzzerella3 (OR 0.768, 95% CI 0.624–0.945) were found to have nominal protective effect against PAH.

Conclusion

The findings from our MR study have revealed a potential causal relationship between gut microbiota and PAH. Specifically, we have identified four types of gut microbiota that exhibit a protective effect on PAH, as well as three types that have a detrimental impact on PAH, thereby offering valuable insights for future mechanistic and clinical investigations in the field of PAH.

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Title: Genetically determined gut microbiota associates with pulmonary arterial hypertension: a Mendelian randomization study
Authors: Ye Yuan
Shan Li
Manrong Yan
Yan Yang
Changming Zhong
Yijie Hu
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Respiratory Microbiota
Arterial Hypertension
Arterial Hypertension
Published in: BMC Pulmonary Medicine / Issue 1/2024
Electronic ISSN: 1471-2466
DOI: https://doi.org/10.1186/s12890-024-02877-2

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