The causal effect of gut microbiome on pulmonary artery hypertension based on a two-sample Mendelian randomization study

Abstract Background Alterations in gut microbiota composition have been linked to the presence of pulmonary artery hypertension (PAH), but it is unclear whether gut microbiota directly causes PAH. Methods A two-sample Mendelian randomization approach was used to investigate the causal association be...

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Main Authors: Detian Jiang, Yuxin Chang, Xiaowen Zhen, Xin Zhao
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Nutrition & Metabolism
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Online Access:https://doi.org/10.1186/s12986-025-00979-0
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author Detian Jiang
Yuxin Chang
Xiaowen Zhen
Xin Zhao
author_facet Detian Jiang
Yuxin Chang
Xiaowen Zhen
Xin Zhao
author_sort Detian Jiang
collection DOAJ
description Abstract Background Alterations in gut microbiota composition have been linked to the presence of pulmonary artery hypertension (PAH), but it is unclear whether gut microbiota directly causes PAH. Methods A two-sample Mendelian randomization approach was used to investigate the causal association between gut microbiota and PAH. Various MR methods were employed, including inverse variance weighted, MR-Egger, weighted median, weighted model, and simple mode, and instrumental variable heterogeneity was assessed using Cochran’s Q statistics. Results Seven bacterial genera were found to be associated with PAH in at least one MR method. Inverse variance weighted analysis showed that UBA7102 sp002315655 (odds ratio [OR] 0.36, 95% confidence interval [CI] 0.17–0.76, P = 0.007) had a protective effect against PAH. Other genera, including Anaeromassilibacillus sp001305115 (OR 1.61, 95% CI: 1.14–2.28, P = 0.006), CAG-776 sp000438195 (OR 1.40, 95% CI 1.10–1.7, P = 0.005), F0428 (OR 1.96, 95% CI 1.27–3.03, P = 0.002), GCA-900,066,495 (OR 1.66, 95% CI: 1.14–2.41, P = 0.007), Leptospirales (OR 5.81, 95% CI 1.53–22.0, P = 0.009) and Paenibacillus J (OR 3.20, 95% CI: 1.53–6.67, P = 0.001), presented a positive association with PAH. No significant instrumental variable heterogeneity was found, and but horizontal pleiotropy was not present in any bacterial taxa. Conclusions This two-sample Mendelian randomization study found that UBA7102 sp002315655, Anaeromassilibacillus sp001305115, CAG-776 sp000438195, F0428, GCA-900,066,495, Leptospirales, and Paenibacillus J may have a causal association with PAH. Further research is needed to determine the underlying mechanisms by which gut microbiota affects PAH.
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spelling doaj-art-901bf1cea6f94013a5f80ba4be9dbc8d2025-08-20T04:01:53ZengBMCNutrition & Metabolism1743-70752025-07-012211710.1186/s12986-025-00979-0The causal effect of gut microbiome on pulmonary artery hypertension based on a two-sample Mendelian randomization studyDetian Jiang0Yuxin Chang1Xiaowen Zhen2Xin Zhao3Department of Cardiovascular Surgery, Qilu Hospital of Shandong University (Qingdao)Department of Emergency, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Hospital)Department of Emergency, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Hospital)Department of Cardiovascular Surgery, Qilu Hospital of Shandong UniversityAbstract Background Alterations in gut microbiota composition have been linked to the presence of pulmonary artery hypertension (PAH), but it is unclear whether gut microbiota directly causes PAH. Methods A two-sample Mendelian randomization approach was used to investigate the causal association between gut microbiota and PAH. Various MR methods were employed, including inverse variance weighted, MR-Egger, weighted median, weighted model, and simple mode, and instrumental variable heterogeneity was assessed using Cochran’s Q statistics. Results Seven bacterial genera were found to be associated with PAH in at least one MR method. Inverse variance weighted analysis showed that UBA7102 sp002315655 (odds ratio [OR] 0.36, 95% confidence interval [CI] 0.17–0.76, P = 0.007) had a protective effect against PAH. Other genera, including Anaeromassilibacillus sp001305115 (OR 1.61, 95% CI: 1.14–2.28, P = 0.006), CAG-776 sp000438195 (OR 1.40, 95% CI 1.10–1.7, P = 0.005), F0428 (OR 1.96, 95% CI 1.27–3.03, P = 0.002), GCA-900,066,495 (OR 1.66, 95% CI: 1.14–2.41, P = 0.007), Leptospirales (OR 5.81, 95% CI 1.53–22.0, P = 0.009) and Paenibacillus J (OR 3.20, 95% CI: 1.53–6.67, P = 0.001), presented a positive association with PAH. No significant instrumental variable heterogeneity was found, and but horizontal pleiotropy was not present in any bacterial taxa. Conclusions This two-sample Mendelian randomization study found that UBA7102 sp002315655, Anaeromassilibacillus sp001305115, CAG-776 sp000438195, F0428, GCA-900,066,495, Leptospirales, and Paenibacillus J may have a causal association with PAH. Further research is needed to determine the underlying mechanisms by which gut microbiota affects PAH.https://doi.org/10.1186/s12986-025-00979-0Gut microbiotaPulmonary artery hypertensionMendelian randomization
spellingShingle Detian Jiang
Yuxin Chang
Xiaowen Zhen
Xin Zhao
The causal effect of gut microbiome on pulmonary artery hypertension based on a two-sample Mendelian randomization study
Nutrition & Metabolism
Gut microbiota
Pulmonary artery hypertension
Mendelian randomization
title The causal effect of gut microbiome on pulmonary artery hypertension based on a two-sample Mendelian randomization study
title_full The causal effect of gut microbiome on pulmonary artery hypertension based on a two-sample Mendelian randomization study
title_fullStr The causal effect of gut microbiome on pulmonary artery hypertension based on a two-sample Mendelian randomization study
title_full_unstemmed The causal effect of gut microbiome on pulmonary artery hypertension based on a two-sample Mendelian randomization study
title_short The causal effect of gut microbiome on pulmonary artery hypertension based on a two-sample Mendelian randomization study
title_sort causal effect of gut microbiome on pulmonary artery hypertension based on a two sample mendelian randomization study
topic Gut microbiota
Pulmonary artery hypertension
Mendelian randomization
url https://doi.org/10.1186/s12986-025-00979-0
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