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Background <p>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.</p> Methods <p>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.</p> Results <p>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, <i>P</i> = 0.007) had a protective effect against PAH. Other genera, including Anaeromassilibacillus sp001305115 (OR 1.61, 95% CI: 1.14–2.28, <i>P</i> = 0.006), CAG-776 sp000438195 (OR 1.40, 95% CI 1.10–1.7, <i>P</i> = 0.005), F0428 (OR 1.96, 95% CI 1.27–3.03, <i>P</i> = 0.002), GCA-900,066,495 (OR 1.66, 95% CI: 1.14–2.41, <i>P</i> = 0.007), Leptospirales (OR 5.81, 95% CI 1.53–22.0, <i>P</i> = 0.009) and Paenibacillus J (OR 3.20, 95% CI: 1.53–6.67, <i>P</i> = 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.</p> Conclusions <p>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.</p>

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

  • 期刊论文

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  • 发表日期：

    2025年7月29日

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  • Detian Jiang,
  • Yuxin Chang,
  • Xiaowen Zhen,
  • Xin Zhao

摘要

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.